BackgroundThe imbalance between pro- and anti-inflammatory immune responses plays a pivotal role in chronic obstructive pulmonary disease (COPD) development and progression. To clarify the pathophysiological mechanisms of this disease, we performed a temporal analysis of immune response-mediated inflammatory progression in a cigarette smoke (CS)-induced mouse model with a focus on the balance between Th17 and Treg responses.MethodsC57BL/6 mice were exposed to CS for 1, 3 or 6 months to induce COPD, and the control groups were maintained under filtered air conditions for the same time intervals. We then performed functional (respiratory mechanics) and structural (alveolar enlargement) analyses. We also quantified the NF-κB, TNF-α, CD4, CD8, CD20, IL-17, IL-6, FOXP3, IL-10, or TGF-β positive cells in peribronchovascular areas and assessed FOXP3 and IL-10 expression through double-label immunofluorescence. Additionally, we evaluated the gene expression of NF-κB and TNF in bronchiolar epithelial cells.ResultsOur CS-induced COPD model exhibited an increased proinflammatory immune response (increased expression of the NF-κB, TNF-α, CD4, CD8, CD20, IL-17, and IL-6 markers) with a concomitantly decreased anti-inflammatory immune response (FOXP3, IL-10, and TGF-β markers) compared with the control mice. These changes in the immune responses were associated with increased alveolar enlargement and impaired lung function starting on the first month and third month of CS exposure, respectively, compared with the control mice.ConclusionOur results showed that the microenvironmental stimuli produced by the release of cytokines during COPD progression lead to a Th17/Treg imbalance.

To describe the progression of parenchymal remodeling and metalloproteinases gene expression in earlier stages of emphysema, mice received porcine pancreatic elastase (PPE) instillation and Control groups received saline solution. After PPE instillation (1, 3, 6 hours, 3 and 21 days) we measured the mean linear intercept, the volume proportion of types I and III collagen, elastin, fibrillin and the MMP-1, -8, -12 and -13 gene expression. We observed an initial decrease in type I (at the 3rd day) and type III collagen (from the 6th hour until the 3rd day), in posterior time points in which we detected increased gene expression for MMP-8 and -13 in PPE groups. After 21 days, the type III collagen fibers increased and the type I collagen values returned to similar values compared to control groups. The MMP-12 gene expression was increased in earlier times (3 and 6 hours) to which we detected a reduced proportion of elastin (3 days) in PPE groups, reinforcing the already established importance of MMP-12 in the breakdown of ECM. Such findings will be useful to better elucidate the alterations in ECM components and the importance of not only metalloelastase but also collagenases in earlier emphysema stages, providing new clues to novel therapeutic targets.

ImportanceAlthough consumption of ultraprocessed food has been linked to higher risk of cardiovascular disease, metabolic syndrome, and obesity, little is known about the association of consumption of ultraprocessed foods with cognitive decline.ObjectiveTo investigate the association between ultraprocessed food consumption and cognitive decline in the Brazilian Longitudinal Study of Adult Health.Design, Setting, and ParticipantsThis was a multicenter, prospective cohort study with 3 waves, approximately 4 years apart, from 2008 to 2017. Data were analyzed from December 2021 to May 2022. Participants were public servants aged 35 to 74 years old recruited in 6 Brazilian cities. Participants who, at baseline, had incomplete food frequency questionnaire, cognitive, or covariate data were excluded. Participants who reported extreme calorie intake (<600 kcal/day or >6000 kcal/day) and those taking medication that could negatively interfere with cognitive performance were also excluded.ExposuresDaily ultraprocessed food consumption as a percentage of total energy divided into quartiles.Main Outcomes and MeasuresChanges in cognitive performance over time evaluated by the immediate and delayed word recall, word recognition, phonemic and semantic verbal fluency tests, and Trail-Making Test B version.ResultsA total of 15 105 individuals were recruited and 4330 were excluded, leaving 10 775 participants whose data were analyzed. The mean (SD) age at the baseline was 51.6 (8.9) years, 5880 participants (54.6%) were women, 5723 (53.1%) were White, and 6106 (56.6%) had at least a college degree. During a median (range) follow-up of 8 (6-10) years, individuals with ultraprocessed food consumption above the first quartile showed a 28% faster rate of global cognitive decline (β = −0.004; 95% CI, −0.006 to −0.001; P = .003) and a 25% faster rate of executive function decline (β = −0.003, 95% CI, −0.005 to 0.000; P = .01) compared with those in the first quartile.Conclusions and RelevanceA higher percentage of daily energy consumption of ultraprocessed foods was associated with cognitive decline among adults from an ethnically diverse sample. These findings support current public health recommendations on limiting ultraprocessed food consumption because of their potential harm to cognitive function.

Background Approximately 77% of older adults with dementia in Brazil have not been diagnosed, indicating a major public health issue. Previous epidemiological dementia studies in Brazil were based on data from one geopolitical region. Methods We aimed to estimate the general and subgroup-specific (age, education, and sex) prevalence of dementia and cognitive impairment no dementia (CIND) classification using data from 5,249 participants aged 60 years and older from the ELSI-Brazil, a large nationally representative sample. Participants were classified as having normal cognitive function, CIND, or dementia based on a combination of the individual’s cognitive and functional status. Results We found a general prevalence of 5.8% (95% CI=4.7-7.2) for dementia and 8.1% (95% CI=6.8-9.5) for CIND. Dementia prevalence ranged from 3.2% (60-64 years old) to 42.8% (≥ 90 years old) by age, and from 2.1% (College level or higher) to 16.5% (illiterates) by education. Females had a higher dementia prevalence (6.8%) than males (4.6%). CIND prevalence was similar across age, sex, and education. Conclusions The estimated dementia prevalence is lower than that in previous Brazilian epidemiological studies, but is in line with other Latin American studies. Only 1.2% of the ELSI-Brazil participants reported having a previous diagnosis of dementia, revealing that underdiagnosis is rampant and a common reality. Based on our results and national statistics projections, we estimate that in 2019 there were 1,757,480 million people aged 60 years and older living with dementia in Brazil and, at least, another 2,271,314 million having to deal with some form of cognitive impairment.

BackgroundThe inverse relationship between exercise capacity and its variation over time and both cardiovascular and all-cause mortality suggests the existence of an etiological nexus between cardiometabolic diseases and the molecular regulators of exercise capacity. Coordinated adaptive responses elicited by physical training enhance exercise performance and metabolic efficiency and possibly mediate the health benefits of physical exercise. In contrast, impaired expression of genes involved in mitochondrial biogenesis or protein turnover in skeletal muscle—key biological processes involved in adaptation to physical training—leads to insulin resistance and obesity. Ingestion of fructose has been shown to suppress the exercise-induced GLUT4 response in rat skeletal muscle. To evaluate in greater detail how fructose ingestion might blunt the benefits of physical training, we investigated the effects of fructose ingestion on exercise induction of genes that participate in regulation of mitochondrial biogenesis and protein turnover in rat’s skeletal muscle.MethodsEight-week-old Wistar rats were randomly assigned to sedentary (C), exercise (treadmill running)-only (E), fructose-only (F), and fructose + exercise (FE) groups and treated accordingly for 8 weeks. Blood and quadriceps femoris were collected for biochemistry, serum insulin, and gene expression analysis. Expression of genes involved in regulation of mitochondrial biogenesis and autophagy, GLUT4, and ubiquitin E3 ligases MuRF-1, and MAFbx/Atrogin-1 were assayed with quantitative real-time polymerase chain reaction.ResultsAerobic training improved exercise capacity in both E and FE groups. A main effect of fructose ingestion on body weight and fasting serum triglyceride concentration was detected. Fructose ingestion impaired the expression of PGC-1α, FNDC5, NR4A3, GLUT4, Atg9, Lamp2, Ctsl, Murf-1, and MAFBx/Atrogin-1 in skeletal muscle of both sedentary and exercised animals while expression of Errα and Pparδ was impaired only in exercised rats.ConclusionsOur results show that fructose ingestion impairs the expression of genes involved in biological processes relevant to exercise-induced remodeling of skeletal muscle. This might provide novel insight on how a dietary factor contributes to the genesis of disorders of glucose metabolism.