HERV-W upregulation expression in bipolar disorder and schizophrenia: unraveling potential links to systemic immune/inflammation status.

BACKGROUND: Bipolar disorder (BD) and schizophrenia (SZ) are the two main mental disorders with unknown etiology that significantly impact individuals' quality of life. The potential pro-inflammatory role in their pathogenesis is postulated and Human Endogenous Retrovirus W (HERV-W) is an emerging candidate to modulate this pathogenic finding. HERVs, ancient retroviruses in the human genome, may play roles in inflammation and disease pathogenesis. Despite HERVs' involvement in autoimmune diseases, their influence on mental disorders remains underexplored. Therefore, the aim of this study was to assess the level of HERV-W-env expression and the systemic inflammatory profile through the concentration of IL-2, IL-4, IL-6, IL-10, TNF-α and INF-γ cytokines in BD and SZ patients. RESULTS: All participants showed HERV-W-env expression, but its expression was higher in mental disorder patients (p < 0.01) than in control. When separated, SZ individuals exhibited higher HERV-W expression than the control group (p < 0.01). Higher serum levels of TNF-α and IL-10 were found in BD (p = 0.0001 and p = 0.001, respectively) and SZ (p = 0.01) and p = 0.01, respectively) than in the control group, while SZ showed decreased levels IFN-γ and IL-2 as compared to controls (p = 0.05) and BD patients (p = 0.05), respectively. Higher TNF-α/IL-4 and TNF-α/IL-10 ratios, and lower IFN-γ/IL-10 were observed in BD and SZ patients than controls. Significant negative correlation between HERV-W-env expression and IL-10 (r=-0.47 p < 0.05), as well as positive correlations between HERV-W-env expression and TNF-α/IL-10 or IFN-γ/IL-10 ratios (r = 0.48 p < 0.05 and r = 0.46 p < 0.05, respectively) were found in BD patients. CONCLUSION: These findings suggest not only a potential link between HERV-W-env expression both in BD and SZ, but also a possible involvement of systemic inflammatory status in BD patients.

Beyond pathogens: the intriguing genetic legacy of endogenous retroviruses in host physiology.

The notion that viruses played a crucial role in the evolution of life is not a new concept. However, more recent insights suggest that this perception might be even more expansive, highlighting the ongoing impact of viruses on host evolution. Endogenous retroviruses (ERVs) are considered genomic remnants of ancient viral infections acquired throughout vertebrate evolution. Their exogenous counterparts once infected the host's germline cells, eventually leading to the permanent endogenization of their respective proviruses. The success of ERV colonization is evident so that it constitutes 8% of the human genome. Emerging genomic studies indicate that endogenous retroviruses are not merely remnants of past infections but rather play a corollary role, despite not fully understood, in host genetic regulation. This review presents some evidence supporting the crucial role of endogenous retroviruses in regulating host genetics. We explore the involvement of human ERVs (HERVs) in key physiological processes, from their precise and orchestrated activities during cellular differentiation and pluripotency to their contributions to aging and cellular senescence. Additionally, we discuss the costs associated with hosting a substantial amount of preserved viral genetic material.

Expression of monocyte chemokine receptors in diabetes after non-surgical periodontal treatment: A pilot study.

The aim of this study was to evaluate the effect of non-surgical periodontal treatment in the expression of chemokine receptors, in individuals with Periodontitis, associated or not with Diabetes. Pilot study, which included patients (n = 45) with Periodontitis, associated (n = 25) or not (n = 20) with Diabetes, submitted to the non-surgical periodontal treatment for one month. The expression of chemokine receptors CCR2, CCR5, and CX3CR1 at the mRNA level was evaluated in the peripheral mononuclear cells, as well as the expression of these receptors at the protein level was verified in monocyte subtypes (classical, intermediate, and non-classical monocytes). There was higher expression of CCR2 and CCR5 receptors at the initial visit in the group with Diabetes, with no differences for CX3CR1 (p = 0.002; p = 0.018, and p = 0.896, respectively), without differences after treatment. There was higher expression of CCR2 and CCR5 proteins in the group with Diabetes at the initial visit for classical, intermediate, and nonclassical monocytes, with no differences for CX3CR1 (CCR2: p = 0.004; p = 0.026; p = 0.024; CCR5: 0.045; p = 0.045; p = 0.013; CX3CR1: p = 0.424; p = 0.944; p = 0.392, respectively), without differences after the end of treatment. Concerning each group separately, there were reductions in the expression of CCR2 as well as CCR5 in classical, intermediate, and nonclassical monocytes, and reduction of CX3CR1 in classical monocytes after treatment in the group with Diabetes (p = 0.003; p = 0.006; p = 0.039; p = 0.007; p = 0.006; p = 0.004; p = 0.019, respectively), without differences in the group without Diabetes. The expression of the chemokine receptors CCR2 and CCR5, in patients with Periodontitis associated with Diabetes, is favorably modified after the end of the non-surgical periodontal treatment.

Impact of Exercise Interventions on Sustained Brain Health Outcomes in Frail Older Individuals: A Comprehensive Review of Systematic Reviews.

Several systematic review studies highlight exercise's positive impact on brain health outcomes for frail individuals. This study adopts a Comprehensive Review of reviews (CRs) approach to amalgamate data from existing reviews, focusing on exercise's influence on brain health outcomes in older frail and pre-frail adults. The methodology involves a thorough search of Portuguese, Spanish, and English-indexed databases (i.e., Ebsco Health, Scielo, ERIC, LILACS, Medline, Web of Science, SportDiscus) from 1990 to 2022, with the AMSTAR-2 tool assessing evidence robustness. The search terms "physical exercise", "elderly frail", and "systematic review" were employed. Results: Out of 12 systematically reviewed studies, four presented high-quality (with metanalyses), while eight exhibit critically low quality. Positive trends emerge in specific cognitive and neuromotor aspects, yet challenges persist in psychosocial domains, complex cognitive tasks, and ADL outcomes. This study yields reasonable and promising evidence regarding exercise's influence on quality of life and depression in frail older individuals. However, the impact on biochemical markers remains inconclusive, emphasizing the need for standardized methodologies. Conclusions: The findings highlight the importance of acknowledging methodological nuances for clinicians and policymakers when translating these results into impactful interventions for aging populations. This emphasizes the necessity for a comprehensive and customized approach to exercise interventions aimed at fostering the sustainability of overall well-being in older individuals, aligning with United Nations Sustainable Development Goal 3.

Prevalence of associations among sarcopenia, obesity, and metabolic syndrome in Brazilian older adults.

Background: Although aging is a process associated with the development of obesity, metabolic syndrome (MetS), and sarcopenia, the prevalence of these conditions in older adults from São Paulo, Brazil, is unclear. Methods: Therefore, the current study aimed to investigate the prevalence of obesity, sarcopenia, and MetS, both separately and together, in a community-based sample of older adults from São Paulo, Brazil. Data from the medical records of 418 older adults of both genders, aged 60 years or older (mean age 69.3 ± 6.5 years), who were not physically active, were used to conduct this retrospective cross-sectional study. Anthropometric variables were used to determine both body mass index (BMI) and Conicity index (C index). Sarcopenia and MetS were defined according to the criteria of the European Working Group on Sarcopenia in Older People and by the Brazilian Society of Endocrinology and Metabolism, respectively. Results: Based on BMI, the group of older men (n = 91) showed a predominance of adequate weight (n = 49) and the group of older women (n = 327) showed a predominance of obesity (n = 181). In association with obesity, while only the group of older women presented with sarcopenia (n = 5), 52 older women and 9 older men presented with MetS, and two older women presented with sarcopenia + MetS [prevalence ratio = 0.0385, 95% CI (0.007;0.1924)]. Based on the C index, 58 older women and 11 older men presented with MetS, while the occurrence of sarcopenia or MetS + sarcopenia was found in 32 and 5 older women, respectively [prevalence ratio = 0.0910, 95% CI (0.037;0.2241)]. Discussion: Our results suggest that obesity, as measured by BMI or the C Index, was more closely associated with the occurrence of MetS than sarcopenia, regardless of gender, and also that sarcopenic obesity was only found in the group of older women. Additionally, the prevalence ratio of obesity, sarcopenia, and MetS evidenced using the C index was 2.3 times higher than the values found using the BMI classification.

Association among inflammaging, body composition, physical activity, and physical function tests in physically active women.

Background: Inflammaging is a phenomenon that has been associated with the development and progression of sarcopenia and frailty syndrome. According to the literature, on the one side, the increase in body fat is associated with a systemic pro-inflammatory status, which consequently favors inflammaging, and on the other side, the regular practice of physical exercise can mitigate the development of this scenario. Therefore, here, we aimed to evaluate the association between inflammaging and physical factors, both body and functional, in a group of physically active older women. Methods: Seventy older women (mean age 72.66 ± 6.17 years) participated in this observational cross-sectional and were separated into the eutrophic, overweight, and obese groups. It was assessed: by bioimpedance-body fat percentage (Fat%) and total (Fat kg), skeletal muscle mass (muscle), and free fat mass both in percentage (FFM%) and total (FFMkg); by the International Physical Activity Questionnaire (IPAQ)-the time of moderate-intensity physical activity per week; by physical tests-handgrip (HG), sit-up-stand-on-the-chair in 5 repetitions (Sit-up) and vertical squat jump test (SJ); in addition to the determination of serum cytokine concentration (IL-6, TNF-α, IL-10, and IL-8), and also body mass index (BMI) and calf circumference (Calf). Results: Higher FFM% and lower body fat (both kg and %) were found in the eutrophic group than in the other groups. The eutrophic group also performed more weekly physical activity, jumped higher, and presented not only higher serum IL-6 concentration but also an increased ratio of IL-10/IL-6, IL-10/TNF-α, IL-10/IL-8 as compared to the values found in the overweight group. The obese group presented higher body fat (kg and %) and lower FFM% than the other groups and also higher serum IL-6 concentration than the overweight group. Interestingly, several significant negative and positive correlations between body composition, physical tests, and serum cytokine concentrations were found in the eutrophic and obese groups. Conclusion: While the eutrophic older women group showed a remarkable regulation of the systemic inflammatory status with positive associations in the physical parameters assessed, the overweight and obese groups presented impairment regulations of the inflammaging, which could be related to less weekly physical activity and higher body fat.

Cellular and Humoral Immune Responses to Vaccination for COVID-19 Are Negatively Impacted by Senescent T Cells: A Case Report.

BACKGROUND: Herein, we aimed to follow up on the cellular and humoral immune responses of a group of individuals who initially received the CoronaVac vaccine, followed by a booster with the Pfizer vaccine. METHODS: Blood samples were collected: before and 30 days after the first CoronaVac dose; 30, 90, and 180 days after the second CoronaVac dose, and also 20 days after the booster with the Pfizer vaccine. RESULTS: Whilst the positivity to gamma interferon-type cellular response increased after the first CoronaVac dose, neutralizing and IgG antibody levels only raised 30 days after the second dose, followed by a drop in these responses after 90 and 180 days. The booster with the Pfizer vaccine elicited a robust cellular and humoral response. A higher number of double-negative and senescent T cells, as well as increased pro-inflammatory cytokines levels were found in the participants with lower humoral immune responses. CONCLUSION: CoronaVac elicited an early cellular response, followed by a humoral response, which dropped 90 days after the second dose. The booster with the Pfizer vaccine significantly enhanced these responses. Furthermore, a pro-inflammatory systemic status was found in volunteers who presented senescent T cells, which could putatively impair the immune response to vaccination.

Monocyte chemokine receptors as therapeutic targets in cardiovascular diseases.

Chemokine receptors are fundamental in many processes related to cardiovascular diseases, such as monocyte migration to vessel walls, cell adhesion, and angiogenesis, among others. Even though many experimental studies have shown the utility of blocking these receptors or their ligands in the treatment of atherosclerosis, the findings in clinical research are still poor. Thus, in the current review we aimed to describe some promising results concerning the blockade of chemokine receptors as therapeutic targets in the treatment of cardiovascular diseases and also to discuss some challenges that need to be overcome before using these strategies in clinical practice.

Impact of Chronic Rhinosinusitis with Nasal Polyposis on IL-12 and IL-8.

Introduction: The pathophysiology of Chronic Rhinosinusitis is coordinated by distinct inflammatory reactions in different individuals. Inflammatory environments with a predominance of Th2 lymphocytes tend also to be rich in eosinophils. These environments are common during the formation of nasal polyps associated with aspirin intolerance, which is also marked by an increase in inflammatory mediators, especially IL-4, IL-5, and IL-13. Despite the significance of these inflammatory mediators, the relevance of IL-12 subunits' presence within eosinophilic nasal polyps, however, has been less studied. The current study aims to evaluate the presence of IL-12 subunits, IL-12p40 and IL-12p70, in eosinophilic nasal polyps and their correlations with IL-8 presence. Materials and Methods: We compared the concentrations of IL-8, IL12p40, and IL12p70 among samples of eosinophilic nasal polypoid tissue, eosinophilic nasal polypoid tissue associated with aspirin intolerance, and healthy nasal mucosa, using an indirect immunoassay (ELISA) kit. Results: When compared to healthy nasal mucosa, there was a lower concentration of IL-8 in Chronic Rhinosinusitis with Nasal Polyp (CRSwNP) tissue. Aspirin Intolerant polypoid tissue also presented a lower concentration of IL-12 subunits compared to healthy nasal mucosa. There was no significant correlation between IL-8 and IL-12 in the eosinophilic polypoid conditions. Conclusion: In CRSwNP, there is a reduction in IL-8 and IL-12 subunits compared to control, with a lack of correlation between IL-12 and IL-8. The lack of correlation can be justified by a type two inflammatory storm environment.

Older Adults Who Maintained a Regular Physical Exercise Routine before the Pandemic Show Better Immune Response to Vaccination for COVID-19.

BACKGROUND: In this study, we aimed to investigate the specific-antibody response to the COVID-19 vaccination and the immunophenotyping of T cells in older adults who were engaged or not in an exercise training program before the pandemic. METHODS: Ninety-three aged individuals (aged between 60 and 85 years) were separated into 3 groups: practitioners of physical exercise vaccinated with CoronaVac (PE-Co, n = 46), or vaccinated with ChadOx-1 (PE-Ch, n = 23), and non-practitioners vaccinated with ChadOx-1 (NPE-Ch, n = 24). Blood samples were collected before (pre) and 30 days after vaccination with the second vaccine dose. RESULTS: Higher IgG levels and immunogenicity were found in the PE-Ch and NPE-Ch groups, whereas increased IgA levels were found only in the PE-Ch group post-vaccination. The PE-Co group showed a positive correlation between the IgA and IgG values, and lower IgG levels post-vaccination were associated with age. Significant alterations in the percentage of naive (CD28+CD57-), double-positive (CD28+CD57+), and senescent (CD28-CD57+) CD4+ T and CD8+ T cells were found post-vaccination, particularly in the PE-Ch group. CONCLUSIONS: The volunteers vaccinated with the ChadOx-1 presented not only a better antibody response but also a significant modulation in the percentage of T cell profiles, mainly in the previously exercised group.

Irisin: An anti-inflammatory exerkine in aging and redox-mediated comorbidities.

Human beings lead largely sedentary lives. From an evolutionary perspective, such lifestyle is not beneficial to health. Exercise can promote many enabling pathways, particularly through circulating exerkines, to optimize individual health and quality of life. Such benefits might explain the protective effects of exercise against aging and noncommunicable diseases. Nevertheless, the miRNA-mediated molecular mechanisms and exerkine interorgan crosstalk that underlie the beneficial effects of exercise remain poorly understood. In this mini review, we focused on the exerkine, irisin, mainly produced by muscle contraction during adaptation to exercise and its beneficial effects on body homeostasis. Herein, the complex role of irisin in metabolism and inflammation is described, including its subsequent effects on thermogenesis through browning to control obesity and improve glycemic regulation for diabetes mellitus control, its potential to improve cognitive function (via brain derived neurotrophic factor), and its pathways of action and role in aging.

Assessment of the Interferon-Lambda-3 Polymorphism in the Antibody Response to COVID-19 in Older Adults Seropositive for CMV.

BACKGROUND: Here, we investigated the impact of IFN-lambda-3 polymorphism on specific IgG responses for COVID-19 in older adults seropositive for CMV. METHODS: Blood samples of 25 older adults of both sexes were obtained at three different times: during a micro-outbreak (MO) of SARS-CoV-2 in 2020; eight months after (CURE); and 30 days after the administration of the second dose of ChadOx-1 vaccine (VAC). The specific IgG for both SARS-CoV-2 and CMV antigens, neutralizing antibodies against SARS-CoV-2, and also the polymorphism profile for IFN-lambda-3 (rs12979860 C > T) were assessed. RESULTS: Higher levels of specific IgG for SARS-CoV-2 antigens were found in the MO and VAC than in the CURE time-point. Volunteers with specific neutralizing antibodies against SARS-CoV-2 showed better specific IgG responses for SARS-CoV-2 and lower specific IgG levels for CMV than volunteers without specific neutralizing antibodies. Significant negative correlations between the specific IgG levels for SARS-CoV-2 and CMV were found at the MO time-point, as well as in the group of individuals homozygous for allele 1 (C/C) in the MO time-point and heterozygotes (C/T) in the CURE time-point. CONCLUSION: Our results suggested that both CMV seropositivity and the homozygosis for allele 1 (C/C) in IFN-lambda-3 gene can negatively impact the antibody response to COVID-19 infection and vaccination in older adults.

Human endogenous retroviruses and the inflammatory response: A vicious circle associated with health and illness.

Human Endogenous Retroviruses (HERVs) are derived from ancient exogenous retroviral infections that have infected our ancestors' germline cells, underwent endogenization process, and were passed throughout the generations by retrotransposition and hereditary transmission. HERVs comprise 8% of the human genome and are critical for several physiological activities. Yet, HERVs reactivation is involved in pathological process as cancer and autoimmune diseases. In this review, we summarize the multiple aspects of HERVs' role within the human genome, as well as virological and molecular aspects, and their fusogenic property. We also discuss possibilities of how the HERVs are possibly transactivated and participate in modulating the inflammatory response in health conditions. An update on their role in several autoimmune, inflammatory, and aging-related diseases is also presented.

Three-dimensional cell culture for the study of nasal polyps

Abstract Objectives: Three-dimensional (3D) cell cultures have many applications such as stem cell biology research, new drug discovery, cancer, and Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). This disease is characterized by a significant impact on quality of life and productivity. The diversity of factors that act in the progression of CRSwNP point to the creation of a cell culture model that allows the integration of different cell types with extracellular matrix. This work aimed to create a cell culture model in 3 dimensions (spheroids) for the study of Nasal Polyposis. Methods: Nasal polyp tissue from patients diagnosed with CRSwNP was mechanically dissociated using tweezers and a scalpel and the solution containing cells and small aggregates of nasal polyps was transferred to a Petri dish containing 5 mL of culture medium at the concentration of 106 cells/mL. Results: The spheroids were cultivated for 20 days, fixed and analyzed using confocal microscopy. In a 3D culture environment, the spheroids were formed both by clustering cells and from small tissue fragments. In the cultures analyzed, the ciliary beat was present from the dissociation of the cells up to 20 days in culture. Conclusion: Our findings also point to these characteristics showing the environment generated in our study, the cells remained differentiated for a longer time and with ciliary beating. Thus, this work shows that nasal polyp-derived cells can be maintained in a 3D environment, enabling better strategies for understanding CRSwNP in situations similar to those found in vivo. Level of evidence: Laboratory studies.

Evaluation of palatal dimensions in different facial patterns by using digital dental casts.

OBJECTIVE: To analyze the variations of hard palate volume in adults with normal occlusion and different facial types and patterns, by using a three-dimensional analysis on digital casts. METHODS: The dental casts of 70 Caucasian adults (28 men, 42 women), mean age of 16.4 years (SD 1.3 years), were scanned by using a tridimensional scanner (Delcam PowerSHAPE™, 2010, Birmingham, UK). Close points were selected in the gingival and cervical regions on the lingual surface of the maxillary teeth, to analyze palatal morphology. The facial patterns and types, and the measurements (width, length, height, volume) of the space on the hard palate were compared using analysis of covariance (ANCOVA), with age as the covariate, and sex as the independent variable. The significance level of 5% (p < 0.05) was adopted. RESULTS: This study showed that the measurements of the width and length were similar among the mesofacial, dolichofacial and brachyfacial facial types, although the height and volume of the space on the hard palate were slightly smaller in dolichofacial individuals, and both Pattern I and Pattern II individuals showed no significant changes for the four measurements. The mean values among facial patterns were: Pattern I - width 38.31±2.59 mm; length 37.44±2.42 mm; height 17.03±2.42 mm and volume 10.52±1.72 mm3; Pattern II - width 37.48±2.44 mm; length 37.48±2.44 mm; height 16.79±2.42 mm and volume 10.41±1.65 mm3 (p>0.05 for all variables). CONCLUSION: There were no significant differences for the facial patterns and facial types of the individuals compared in the analyzed sample.

Effects of physical distancing by COVID-19 pandemic on diet quality, neurological and immunological markers, and fecal microbiota of Brazilian older women.

Physical distancing was used to prevent transmission of COVID-19, however there are concerns that this may promote harmful impacts on health, such as reduced levels of physical practice and changes in food intake and gut microbiota composition. This study evaluated the impacts of 6 months physical distancing on Brazilian older women upon body mass index (BMI), strength, physical activity level (IPAQ), eating habits, neurological markers (brain-derived neurotrophic factor-BDNF and cortisol), cytokines (IL-2, IL-5, IL-6, IL-10, interferon-IFN-γ, tumor necrosis factor-TNF-α), aging-associated markers (vascular endothelial growth factor-VEGF, insulin-like growth factor-IGF-1, klotho and thymic stromal lymphopoietin-TSLP), besides specific groups of fecal microbiota. Fifteen women, over 60 years old, residents of São Paulo state (Brazil), were evaluated in March and in September 2020. The older adult women, with a mean age 66 ± 6.2 years presented significantly increased BMI and high effect size for non-protective foods consumption, reduced light physical activity and strength 6 months following the physical distancing. Furthermore, the serum concentration of IFN-γ, IGF-1, and IFN-γ/IL-5 were significantly higher, while lower concentration of IL-2 and IL-5 were observed 6 months after the physical distancing. Significant increase was noted only to Blautia spp. abundance after 6 months of physical distancing. Several correlations were observed at both before and after physical distancing, however, interestingly, many of them were lost or inverted 6 months following, while new ones emerged. Taken together, these results showed that lifestyle changes and stress conditions addressed by physical distancing from the COVID-19 pandemic impacted the health of older women included in the present study. Therefore, future follow-up studies are essential to propose interventions in order to restore the health conditions observed before the pandemic period, and thus to maintain the quality of life of older adults in different socioeconomic contexts.

Older Women Who Practiced Physical Exercises before the COVID-19 Pandemic Present Metabolic Alterations and Worsened Functional Physical Capacity after One Year of Social Isolation.

BACKGROUND: Because the consequences of the lifestyle changes in older adults associated with the social isolation imposed in response to the COVID-19 pandemic are not fully understood, here, we investigated the effects of one year of social isolation imposed by COVID-19 on the metabolic parameters and functional physical capacity of older women who regularly practiced physical exercises before the pandemic. METHODS: Systemic lipid and protein profiles, estimated creatinine clearance (ECC), and functional physical capacity (FPC) were assessed before (January-February 2020) and 12 months after social isolation in 30 older women (mean age 73.77 ± 6.22) who were engaged in a combined-exercise training program for at least 3 years before the COVID-19 pandemic. RESULTS: In this group, we observed increased plasma levels of triglycerides and creatinine, an increase in the time necessary to perform gait speed and time-up-and-go tests, and reduced muscle strength assessed by the handgrip test and ECC post-COVID-19 pandemic relative to values recorded pre-pandemic. In addition, we observed significant correlations (both negative and positive) between anthropometric, some metabolic parameters, and physical tests. CONCLUSION: One year of interruption of physical exercise practice imposed in response to the COVID-19 pandemic significantly altered some systemic metabolic parameters and worsened ECC and FPC in older women.

Combined resistance and aerobic training improves lung function and mechanics and fibrotic biomarkers in overweight and obese women.

Background: Obesity impairs lung function and mechanics and leads to low-grade inflammation, but the effects of combined physical exercise (CPE) on that are unknown. Methods: We investigated the effects of 12 weeks of combined physical exercise (aerobic + resistance training), in non-obese (n = 12), overweight (n = 17), and obese grade I (n = 11) women. Lung function and lung mechanics were evaluated. The systemic immune response was evaluated by whole blood analysis and biomarker measurements, while pulmonary fibrotic biomarkers were evaluated in the breath condensate. Result: CPE improved forced vital capacity (FVC) % (p < 0.001) and peak expiratory flow (PEF) % (p < 0.0003) in the obese group; resistance of the respiratory system (R5Hz) in non-obese (p < 0.0099), overweight (p < 0.0005), and obese (p < 0.0001) groups; resistance of proximal airways (R20Hz) in non-obese (p < 0.01), overweight (p < 0.0009), and obese (p < 0.0001) groups; resistance of distal airways (R5Hz-R20Hz) in non-obese (p < 0.01), overweight (p < 0.0012), and obese (p < 0.0001) groups; reactance of the respiratory system (X5Hz) in non-obese (p < 0.01), overweight (p < 0.0006), and obese (p < 0.0005) groups; impedance of the respiratory system (Z5Hz) in non-obese (p < 0.0099), overweight (p < 0.0005), and obese (p < 0.0001) groups; central resistance (RCentral) in non-obese (p < 0.01), overweight (p < 0.001), and obese (p < 0.0003) groups; and the peripheral resistance (RPeripheral) in non-obese (p < 0.03), overweight (p < 0.001), and obese (p < 0.0002) groups. CPE reduced the pro-fibrotic IGF-1 levels in BC in overweight (p < 0.0094) and obese groups (p < 0.0001) and increased anti-fibrotic Klotho levels in BC in obese (p < 0.0001) groups, and reduced levels of exhaled nitric oxide in overweight (p < 0.03) and obese (p < 0.0001) groups. Conclusion: CPE improves lung function, mechanics, and pulmonary immune response in overweight and obese grade I women by increasing anti-fibrotic protein Klotho and reducing pro-fibrotic IGF-1.

Metabolic and immune/inflammatory alterations induced by a triathlon under extreme conditions.

Purpose: To investigate the effects of triathlon racing under extreme conditions on metabolic and immune/inflammatory responses. Methods: Thirteen amateur athletes participated in an extreme triathlon competition (swim - 3.8 km; cycling - 180 km; running - 4 2 km; with a 3,700 m accumulated altitude). Blood samples were collected on three different occasions: pre-competition (baseline), immediately post-competition (IM), and 12 h post-competition (12 h) to evaluate glycemic and lipid profiles, leukocytes count, and cytokines levels in plasma and in whole-blood cell culture supernatant stimulated or not with LPS. Results: Decreased glucose and triglycerides levels, increased LDL, and a significant leukocytosis were observed at IM and 12 h compared to baseline. In addition, higher serum levels of IL-6, IL-8, and IL-10 were found at IM than in baseline and post-12 h. Whereas increased IL-12p40 levels were observed for 12 h compared to baseline. At baseline, in LPS-stimulated cell culture, IL-6, IL-8, and IL-12p70 were higher, while IL-12p40 levels were lower than non-stimulated cell culture. At IM, IL-12p40 levels were unchanged, while higher levels of other cytokines were found in LPS-stimulated cell culture compared to non-stimulated cell culture. The 12 h results showed higher levels of IL-6, IL-8, and IL-10 in LPS-stimulated cell culture than in non-stimulated cell culture. Additionally, a significant negative correlation between circulating glucose levels and IL-6 was found. Conclusion: The triathlon competition's performance under extreme conditions has remarkable impacts on the lipid profile and systemic immune/inflammatory responses. For the first time, significant alterations in the cytokine responses of whole blood cell culture to LPS-stimulation in baseline, IM, and 12h were demonstrated.