Exposure to urban ambient particles (PM2.5) before pregnancy affects the expression of endometrial receptive markers to embryo implantation in mice: Preliminary results.

Air pollution (AP) is one of the main recent concerns in reproductive healthy due to its potential to promote negative outcomes during pregnancy and male and female fertility. Several studies have demonstrated that AP exposure has been linked to increased embryonic implantation failures, alterations in embryonic, fetal and placental development. For a well-succeeded implantation, both competent blastocyst and receptive endometrium are required. Based on the lack of data about the effect of AP in endometrial receptivity, this study aimed to evaluate he particulate matter (PM) exposure impact on uterine receptive markers in mice and associate the alterations to increased implantation failures due to AP. For this study, ten dams per group were exposed for 39 days to either filter (F) or polluted air (CAP). At fourth gestational day (GD4), females were euthanized. Morphological, ultrastructural, immunohistochemical and molecular analysis of uterine and ovarian samples were performed. CAP-exposed females presented a reduced number of corpus luteum; glands and epithelial cells were increased with pinopodes formation impairment. Immunohistochemistry analysis revealed decreased LIF protein levels. These preliminary data suggests that PM exposure may exert negative effects on endometrial receptivity by affecting crucial parameters to embryonic implantation as uterine morphological differentiation, corpus luteum quantity and LIF expression during implantation window.

Lactobacillus rhamnosus Modulates Lung Inflammation and Mitigates Gut Dysbiosis in a Murine Model of Asthma-COPD Overlap Syndrome.

The asthma-COPD overlap syndrome (ACOS) presents lung inflammation similar to both asthma and chronic obstructive pulmonary disease (COPD). Due to the immune response between the lung and gut, it is possible that ACOS individuals present gut dysbiosis. Due to therapeutic limitations in ACOS, Lactobacillus rhamnosus (Lr) have received attention once Lr has been effective in asthma and COPD. However, there is no data about the Lr effect on both lung inflammation and gut dysbiosis in ACOS. Thus, our study investigated the Lr effect on lung inflammation, bronchoconstriction, airway remodeling, and gut dysbiosis in the murine ACOS model. Treated mice with Lr were exposed to HDM and cigarette smoke to induce ACOS. Sixty days after ACOS induction, mice were euthanized. Lung inflammation was evaluated in leukocytes in bronchoalveolar lavage fluid (BALF), airway remodeling, cytokine secretion, and transcription factor expression in the lung. The gut microbiota was assayed by 16S mRNA sequencing from a fecal sample. Leukocyte population, bronchial hyperreactivity, pro-inflammatory cytokines, and airway remodeling were attenuated in Lr-treated ACOS mice. Likewise, IL-4, IL-5, and IL-13, STAT6 and GATA3, as well as IL-17, IL-21, IL-22, STAT3, and RORÉ£t were reduced after Lr. In addition, IL-2, IL-12, IFN-γ, STAT1, and T-bet as well as IL-10, TGF-ß, STAT5, and Foxp3 were restored after the Lr. Firmicutes was reduced, while Deferribacteres was increased after Lr. Likewise, Lr decreased Staphylococcus and increased Mucispirillum in ACOS mice. Lr improves fecal bacterial ß-diversity. Our findings show for the first time the Lr effect on lung inflammation and gut dysbiosis in murine ACOS.

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.

Resistance exercise shifts the balance of renin-angiotensin system toward ACE2/Ang 1-7 axis and reduces inflammation in the kidney of diabetic rats.

AIMS: We aimed to determine whether resistance training (RT) regulates renal renin-angiotensin system (RAS) components and inflammatory mediators in diabetic rats. MAIN METHODS: Male Wistar rats (3 months old) were randomly assigned into four groups: non-trained (NT), trained (T), non-trained + diabetes (NTD) and trained +diabetes (TD). Diabetes was induced by streptozotocin (50 mg/kg, Sigma Chemical Co., St. Louis, MO, USA), before RT protocol. Trained rats performed RT protocol on a 110-cm ladder (8 ladder climbs, once/day, 5 days/week, 8 weeks), carrying a load corresponding to 50-80% of maximum carrying capacity. Blood glucose, albuminuria and urinary volume were measured. Renal levels of angiotensin peptides (angiotensin I, II and 1-7), inflammatory markers, and also the activities of angiotensin-converting enzyme (ACE) and ACE2 were determined. KEY FINDINGS: Blood glucose and urinary volume were elevated in diabetic animals, and RT decreased albuminuria, renal Ang I and Ang II levels in diabetic rats. RT shifted the balance of renal RAS toward ACE2/Ang 1-7 axis in TD group, and mitigated the high levels of interleukin (IL)-10, IL-1ß and cytokine-induced neutrophil chemoattractant 1 (CINC) in the context of diabetes. Strong positive correlations were found between albuminuria and Ang II, IL-10 and IL-1ß. On the other hand, intrarenal Ang 1-7 levels were negatively correlated with IL-10 and IL-1ß levels. SIGNIFICANCE: RT improved kidney function by modulating intrarenal RAS toward ACE2/Ang 1-7 axis and inflammatory cytokines. RT represents a reasonable strategy to improve the renal complications induced by diabetes, counteracting nephropathy-associated maladaptive responses.

Low-level laser therapy alleviates the deleterious effect of doxorubicin on rat adipose tissue-derived mesenchymal stem cells.

Cancer is a leading cause of death worldwide, and doxorubicin (DOX) has become one of the most commonly prescribed drugs. Stem cell (SC) therapy is proving to be a promising strategy to alleviate DOX adverse effects on non-cancerous cells. However, the drug also has a toxic action on SCs, reducing the efficiency of cell therapy from a preventive view. The present study shows that the DOX toxicity in mesenchymal SCs (MSCs) can be partially overcome by low-level laser irradiation (LLLI). To achieve this, we applied the low-level red laser (wavelength: 660 nm; output power: 30 mW; laser beam: 0.028 cm2; irradiation: 1.07 mW/cm2; Ga-Al-As Photon Laser III, DMC, São Paulo, Brazil) in rat adipose tissue-derived MSCs before their exposure to different DOX concentrations. Results revealed that the DOX reduced the viability and adenosine triphosphate level of MSCs. These findings were followed by significantly increased apoptosis as well as oxidative stress in the MSCs. Interestingly, LLLI at the dose of 0.2 J alleviated the effects of DOX on cell viability and apoptosis, and inhibited oxidative stress in the MSCs. In summary, this study provides a crucial step toward the future application of LLLI as a protective approach against DOX-induced toxicity in MSCs, particularly cell death. This study also lays the groundwork for further investigation into the role of oxidative stress and inflammation as an instructive milieu for cell protection.

Premenstrual Syndrome, Inflammatory Status, and Mood States in Soccer Players.

OBJECTIVE: To evaluate the relationship between the inflammatory profile and mood states in the different phases of the menstrual cycle in soccer players with and without premenstrual syndrome (PMS). METHODS: Data on the menstrual cycle and mood states were collected using the Daily Symptom Report and the Brunel Mood Scale. Cytokine and stress hormone concentrations were measured in urine by flow cytometry before and after a game in the luteal phase and in the follicular phase of one menstrual cycle. RESULTS: In all, 59.6% of the athletes had PMS. The PMS group showed higher concentrations of interleukin (IL)-1ß, IL-6, and IL-8 than the athletes without PMS. After the game, IL-6 decreased in the follicular phase and the luteal phase. The tumor necrosis factor-α levels were higher in the group without PMS during the post-game follicular phase than before the game. In the PMS group, tension was higher in the follicular phase before the game and depression was higher in the pre-game luteal phase than in the group without PMS. The PMS group also presented a negative correlation between depression and IL-10 levels in the pre-game follicular phase. Finally, in the pre-game luteal phase were found positive correlations between growth hormone and IL-10. CONCLUSION: PMS influences the inflammatory condition related to mood states and stress hormones in female soccer players.

Influence of weight loss on pulmonary function and levels of adipokines among asthmatic individuals with obesity: One-year follow-up.

BACKGROUND: Individuals with obesity are more likely to develop asthma, but the exact mechanism is still uncertain and several hypotheses have been raised, such as the release of inflammatory mediators secreted by adipose tissue. OBJECTIVE: To assess the effects of weight loss in patients submitted to bariatric surgery on pulmonary and systemic inflammation. METHOD: The study evaluated patients undergoing bariatric surgery (Roux-en-Y gastric bypass) with the diagnosis of asthma, except smokers. The patients were evaluated at the time of entry into a preoperative weight loss group (T1), just before bariatric surgery (T2), six months after surgery (T3), and 12 months after surgery (T4). The following were measured: anthropometric data, dosage of systemic inflammatory markers by means of blood collection, pulmonary inflammatory markers obtained by induced sputum collection, pulmonary function parameters, and asthma activity assessed by a Asthma Control Test (ACT) questionnaire. RESULTS: Nineteen patients participated in the study. There were significant reductions in the systemic levels of interleukin (IL)-8 (p = 0.002), C-reactive protein (CRP) (p = 0.003), leptin (p = 0.001) and tumor necrosis factor (TNF)-α (p = 0.007), and significant increase in the systemic levels of IL-6 (p = 0.004) over time and adiponectin in T2 (p = 0.025). In regards to pulmonary inflammation, there were significant reductions in the sputum levels of TNF-α (p < 0.001). There was no significant improvement of the pulmonary function parameters (p > 0.05) and significant improvement in asthma activity scores (p < 0.0001). CONCLUSION: Weight loss was associated with significant changes in the systemic and pulmonary inflammatory profiles of individuals with asthma, leading to a better asthma control as a result of an increase in some anti-inflammatory mediators and a reduction of pro-inflammatory mediators.

Author Correction: Low dose of chlorine exposure exacerbates nasal and pulmonary allergic inflammation in mice.

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Low dose of chlorine exposure exacerbates nasal and pulmonary allergic inflammation in mice.

Work-exacerbated asthma (WEA) is defined as preexisting asthma that worsens with exposure to irritants [e.g., chlorine (Cl2) derivatives] in the workplace. The maximum allowable concentration in the workplace of Cl2 exposure is 3 mg/ m3 (described in OSHA). We investigated in an experimental asthma model in mice the effects of a single exposure to a sodium hypochlorite dose with this allowed chlorine concentration and a tenfold higher dose. Acute chlorine exposure at 3.3 mg/m3 in the OVA-sensitized group increased eosinophils in the peribronquial infiltrate, cytokine production, nasal mucus production and the number of iNOS positive cells in the distal lung compared to only sensitized mice. The exposure to a higher dose of 33.3 mg/m3 in the OVA-sensitized group resulted in an increase in respiratory system elastance, in the total and differential numbers of inflammatory cells in bronchoalveolar lavage fluid, IL-4, IL-5, and IL-17 in the lungs, eosinophils in peribronquial infiltrate and mucus content in nasal compared to non-exposed and sensitized animals. In this asthma model, chorine exposures at an allowable dose, contributed to the potentiation of Th2 responses. The functional alterations were associated with increased iNOS and ROCK-2 activation in the distal lung.

Sex-specific variation in signaling pathways and gene expression patterns in human leukocytes in response to endotoxin and exercise.

BACKGROUND: While exercise effects on the immune system have received increasing attention in recent years, it remains unclear to what extent gender and fluctuations in sex hormones during menstrual cycle influence immunological responses to exercise. METHODS: We investigated mRNA changes induced through exhaustive exercise (half-marathon; pre-exercise and post-exercise [30 min, 3 h, 24 h] on whole blood cultures ± lipopolysaccharide [LPS] [1 h]) with a specific focus on sex differences (men vs women in luteal phase) as an extension of our previous study. RESULTS: Inflammation related signaling pathways, TLRs, cytosolic DNA sensing and RIG-I like receptors were differentially activated between sexes in LPS-stimulated cultures. Genes differentially regulated between sexes included TNIP-1, TNIP-3, IL-6, HIVEP1, CXCL3, CCR3, IL-8, and CD69, revealing a bias towards less anti-inflammatory gene regulation in women compared to men. In addition, several genes relevant to brain function (KMO, DDIT4, VEGFA, IGF1R, IGF2R, and FGD4) showed differential activation between sexes. Some of these genes (e.g., KMO in women, DDIT4 in both sexes) potentially constitute neuroprotective mechanisms. CONCLUSIONS: These data reveal that the exercise-induced change in gene expression might be gender and menstrual cycle phase dependent.

C1P Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Preventing NF-κB Activation in Neutrophils.

Recently, ceramide-1-phosphate (C1P) has been shown to modulate acute inflammatory events. Acute lung injury (Arnalich et al. 2000. Infect. Immun. 68: 1942-1945) is characterized by rapid alveolar injury, lung inflammation, induced cytokine production, neutrophil accumulation, and vascular leakage leading to lung edema. The aim of this study was to investigate the role of C1P during LPS-induced acute lung injury in mice. To evaluate the effect of C1P, we used a prophylactic and therapeutic LPS-induced ALI model in C57BL/6 male mice. Our studies revealed that intrapulmonary application of C1P before (prophylactic) or 24 h after (therapeutic) LPS instillation decreased neutrophil trafficking to the lung, proinflammatory cytokine levels in bronchoalveolar lavage, and alveolar capillary leakage. Mechanistically, C1P inhibited the LPS-triggered NF-κB levels in lung tissue in vivo. In addition, ex vivo experiments revealed that C1P also attenuates LPS-induced NF-κB phosphorylation and IL-8 production in human neutrophils. These results indicate C1P playing a role in dampening LPS-induced acute lung inflammation and suggest that C1P could be a valuable candidate for treatment of ALI.