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1.
Int J Mol Sci ; 22(5)2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33807854

ABSTRACT

We observed substantial differences in predicted Major Histocompatibility Complex II (MHCII) epitope presentation of SARS-CoV-2 proteins for different populations but only minor differences in predicted MHCI epitope presentation. A comparison of this predicted epitope MHC-coverage revealed for the early phase of infection spread (till day 15 after reaching 128 observed infection cases) highly significant negative correlations with the case fatality rate. Specifically, this was observed in different populations for MHC class II presentation of the viral spike protein (p-value: 0.0733 for linear regression), the envelope protein (p-value: 0.023), and the membrane protein (p-value: 0.00053), indicating that the high case fatality rates of COVID-19 observed in some countries seem to be related with poor MHC class II presentation and hence weak adaptive immune response against these viral envelope proteins. Our results highlight the general importance of the SARS-CoV-2 structural proteins in immunological control in early infection spread looking at a global census in various countries and taking case fatality rate into account. Other factors such as health system and control measures become more important after the early spread. Our study should encourage further studies on MHCII alleles as potential risk factors in COVID-19 including assessment of local populations and specific allele distributions.

2.
Article in English | MEDLINE | ID: mdl-33807858

ABSTRACT

Heavy metal poisoning has caused serious and widespread human tragedies via the food chain. To alleviate heavy metal pollution, particular attention should be paid to low accumulating vegetables and crops. In this study, the concentrations of five hazardous heavy metals (HMs), including copper (Cu), chromium (Cr), lead (Pb), cadmium (Cd), and arsenic (As) were determined from soils, vegetables, and crops near four typical mining and smelting zones. Nemerow's synthetical pollution index (Pn), Potential ecological risk index (RI), and Geo-accumulation index (Igeo) were used to characterize the pollution degrees. The results showed that soils near mining and metal smelting zones were heavily polluted by Cu, Cd, As, and Pb. The total excessive rate followed a decreasing order of Cd (80.00%) > Cu (61.11%) > As (45.56%) > Pb (32.22%) > Cr (0.00%). Moreover, sources identification indicated that Cu, Pb, Cd, and As may originate from anthropogenic activities, while Cr may originate from parent materials. The exceeding rates of Cu, Cr, Pb, Cd, and As were 6.7%, 6.7%, 66.7%, 80.0%, and 26.7% among the vegetable and crop species, respectively. Particularly, vegetables like tomatoes, bell peppers, white radishes, and asparagus, revealed low accumulation characteristics. In addition, the hazard index (HI) for vegetables and crops of four zones was greater than 1, revealing a higher risk to the health of local children near the mine and smelter. However, the solanaceous fruit has a low-risk index (HI), indicating that it is a potentially safe vegetable type.

3.
Int J Mol Sci ; 22(5)2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33807862

ABSTRACT

Chitosan-based edible coatings represent an eco-friendly and biologically safe preservative tool to reduce qualitative decay of fresh and ready-to-eat fruits during post-harvest life due to their lack of toxicity, biodegradability, film-forming properties, and antimicrobial actions. Chitosan-based coatings modulate or control oxidative stress maintaining in different manner the appropriate balance of reactive oxygen species (ROS) in fruit cells, by the interplay of pathways and enzymes involved in ROS production and the scavenging mechanisms which essentially constitute the basic ROS cycle. This review is carried out with the aim to provide comprehensive and updated over-view of the state of the art related to the effects of chitosan-based edible coatings on anti-oxidant systems, enzymatic and non-enzymatic, evaluating the induced oxidative damages during storage in whole and ready-to-eat fruits. All these aspects are broadly reviewed in this review, with particular emphasis on the literature published during the last five years.

4.
Int J Mol Sci ; 22(5)2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33807864

ABSTRACT

INTRODUCTION: Chronic inflammation and impaired neovascularization play critical roles in delayed wound healing in diabetic patients. To overcome the limitations of current diabetic wound (DBW) management interventions, we investigated the effects of a catechol-functionalized hyaluronic acid (HA-CA) patch combined with adipose-derived mesenchymal stem cells (ADSCs) in DBW mouse models. METHODS: Diabetes in mice (C57BL/6, male) was induced by streptozotocin (50 mg/kg, >250 mg/dL). Mice were divided into four groups: control (DBW) group, ADSCs group, HA-CA group, and HA-CA + ADSCs group (n = 10 per group). Fluorescently labeled ADSCs (5 × 105 cells/100 µL) were transplanted into healthy tissues at the wound boundary or deposited at the HA-CA patch at the wound site. The wound area was visually examined. Collagen content, granulation tissue thickness and vascularity, cell apoptosis, and re-epithelialization were assessed. Angiogenesis was evaluated by immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blot. RESULTS: DBW size was significantly smaller in the HA-CA + ADSCs group (8% ± 2%) compared with the control (16% ± 5%, p < 0.01) and ADSCs (24% ± 17%, p < 0.05) groups. In mice treated with HA-CA + ADSCs, the epidermis was regenerated, and skin thickness was restored. CD31 and von Willebrand factor-positive vessels were detected in mice treated with HA-CA + ADSCs. The mRNA and protein levels of VEGF, IGF-1, FGF-2, ANG-1, PIK, and AKT in the HA-CA + ADSCs group were the highest among all groups, although the Spred1 and ERK expression levels remained unchanged. CONCLUSIONS: The combination of HA-CA and ADSCs provided synergistic wound healing effects by maximizing paracrine signaling and angiogenesis via the PI3K/AKT pathway. Therefore, ADSC-loaded HA-CA might represent a novel strategy for the treatment of DBW.

5.
Article in English | MEDLINE | ID: mdl-33807869

ABSTRACT

The pandemic of the coronavirus disease 2019 (COVID-19) has provoked a second pandemic, the "long-haulers", i.e., individuals presenting with post-COVID symptoms. We propose that to determine the presence of post-COVID symptoms, symptoms should appear after the diagnosis of SARS-CoV-2 infection; however, this situation has some problems due to the fact that not all people infected by SARS-CoV-2 receive such diagnosis. Based on relapsing/remitting nature of post-COVID symptoms, the following integrative classification is proposed: potentially infection related-symptoms (up to 4-5 weeks), acute post-COVID symptoms (from week 5 to week 12), long post-COVID symptoms (from week 12 to week 24), and persistent post-COVID symptoms (lasting more than 24 weeks). The most important topic is to establish the time reference points. The classification also integrates predisposing intrinsic and extrinsic factors and hospitalization data which could promote post-COVID symptoms. The plethora of symptoms affecting multiple systems exhibited by "long-haulers" suggests the presence of different underlying mechanisms.

6.
Int J Mol Sci ; 22(5)2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33807876

ABSTRACT

In the scenario of systemic treatment for advanced non-small cell lung cancer (NSCLC) patients, one of the most relevant breakthroughs is represented by targeted therapies. Throughout the last years, inhibitors of the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-Ros oncogene 1 (ROS1), and V-raf murine sarcoma viral oncogene homolog B (BRAF) have been approved and are currently used in clinical practice. However, other promising molecular drivers are rapidly emerging as therapeutic targets. This review aims to cover the molecular alterations with a potential clinical impact in NSCLC, including amplifications or mutations of the mesenchymal-epithelial transition factor (MET), fusions of rearranged during transfection (RET), rearrangements of the neurotrophic tyrosine kinase (NTRK) genes, mutations of the Kirsten rat sarcoma viral oncogene (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), as well as amplifications or mutations of human epidermal growth factor receptor 2 (HER2). Additionally, we summarized the current status of targeted agents under investigation for such alterations. This revision of the current literature on emerging molecular targets is needed as the evolving knowledge on novel actionable oncogenic drivers and targeted agents is expected to increase the proportion of patients who will benefit from tailored therapeutic approaches.

7.
Int J Mol Sci ; 22(5)2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33807880

ABSTRACT

Two siblings with CF are homozygous for F508del (referred to as Subject A and Subject B). Despite having the same CFTR genotype and similar environment, these two subjects exhibited different disease phenotypes. We analyzed their medical records and CF Foundation Registry data and measured inflammatory protein mediators in their sputum samples. Then, we examined the longitudinal relationships between inflammatory markers and disease severity for each subject and compared between them. Subject A presented a more severe disease than Subject B. During the study period, Subject A had two pulmonary exacerbations (PEs) whereas Subject B had one mild PE. The forced expiratory volume in 1 s (FEV1, % predicted) values for Subject A were between 34-45% whereas for Subject B varied between 48-90%. Inflammatory protein mediators associated with neutrophils, Th1, Th2, and Th17 responses were elevated in sputum of Subject A compared with Subject B, and also in samples collected prior to and during PEs for both subjects. Neutrophilic elastase (NE) seemed to be the most informative biomarkers. The infectious burden between these two subjects was different.

8.
Medicina (Kaunas) ; 57(3)2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33807881

ABSTRACT

Background and Objectives: In patients with diabetes mellitus (DM), the neural retina is starting to degenerate before the development of vascular lesions. Our purpose was to investigate the correlation between the retinal arterial morphometric parameters and structural neurodegeneration in patients with type 2 DM with no or mild diabetic retinopathy (DR). Materials and Methods: This is a prospective study including 53 eyes of patients with type 2 DM and 32 eyes of healthy controls. Based on SD-OCT (spectral domain-optical coherence tomography) images, using a micro-densitometry method, we measured the outer and luminal diameter of retinal arteries and calculated the AWT (arterial wall thickness), WLR (wall-to-lumen ratio), and WCSA (wall cross-sectional area). GCL (ganglion cell layer) and RNFL (retinal nerve fiber layer) thickness were analyzed in correlation with the retinal arterial morphometric parameters mentioned above. Results: GCL was thinner in the inner quadrants in the NDR (no DR) group compared to controls (p < 0.05). RAOD (retinal artery outer diameter), RALD (retinal artery lumen diameter), AWT, WLR, and WCSA were similar between groups. A regression model considering age, gender, duration of DM, and HbA1C was carried out. Central GCL thickness was correlated positively with RAOD (coefficient 0.360 per µm, p = 0.011), RALD (coefficient 0.283 per µm, p = 0.050), AWT (coefficient 0.304 per µm, p = 0.029), and WCSA (coefficient 3.90 per µm, p = 0.005). Duration of DM was positively correlated with WCSA (coefficient 0.311 per one year duration of diabetes, p = 0.043). Conclusions: Significant GCL thinning in the inner quadrants preceded the morphological retinal arterial morphometric changes, supporting the neurodegeneration as primary pathogenic mechanism in DR.

9.
Article in English | MEDLINE | ID: mdl-33807889

ABSTRACT

In recent years, neuroscience and neurodidactics have demonstrated significant progress in improving the teaching and learning process for various subjects, such as physical education [...].

10.
Article in English | MEDLINE | ID: mdl-33807890

ABSTRACT

Noncommunicable diseases (NCDs) and their underlying risk factors are seen as major public health problems that threaten health and welfare systems worldwide. The holistic and resource oriented Health Promoting School (HPS) approach can serve as an appropriate framework for the prevention and control of NCDs. The paper aimed to map the implementation of HPS activities in German schools and to examine associations with potential influencing factors. A series of cross-sectional online studies including five federal states and 5006 school principals (40.2% males, 50.8% females) from primary and secondary public schools was conducted from 2013 to 2018. Principal component analysis (PCA) resulted in two factors of HPS implementation (F1: concrete HPS action, F2: capacity building for HPS). Comparing both factors, a lower implementation level could be identified for HPS capacity building with lowest mean values found for regular teacher training and intersectoral collaboration. Multiple binary regression analyses revealed significant associations between low HPS implementation and male gender (OR: 1.36 to 1.42), younger age (OR: 1.47 to 1.90), secondary school (OR: 1.78 to 3.13) and federal state (Lower Saxony = OR: 1.27 to 1.45; Schleswig-Holstein = OR: 1.95 to 2.46). Moreover, low access to resources, decision-latitude and perceived educational benefits were independently associated with both factors of HPS implementation. Based on the results of this study, there is a need to support schools in their capacity building for health (e.g., regular teacher training, cooperation with local health services). Moreover, considering the core mission of schools, more evidence of the educational impact of health promotion and its translation into the language of education is needed for secondary schools in particular.

11.
Molecules ; 26(5)2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33807893

ABSTRACT

Oil droplets containing surfactants and pesticides are expected to spread on a water surface, under the Marangoni effect, depending on the surfactant. Pesticides are transported into water through this phenomenon. A high-speed video camera was used to measure the movement of Marangoni ridges. Gas chromatography with an electron capture detector was used to analyze the concentration of the pesticide in water at different times. Oil droplets containing the surfactant and pesticide spread quickly on the water surface by Marangoni flow, forming an oil film and promoting emulsification of the oil-water interface, which enabled even transport of the pesticide into water, where it was then absorbed by weeds. Surfactants can decrease the surface tension of the water subphase after deposition, thereby enhancing the Marangoni effect in pesticide-containing oil droplets. The time and labor required for applying pesticides in rice fields can be greatly reduced by using the Marangoni effect to transport pesticides to the target.

12.
Article in English | MEDLINE | ID: mdl-33807896

ABSTRACT

Farmers are at a high risk of inhalation exposure when handling pesticides. Thai farmers usually protect themselves against pesticide exposure by wearing commercial respiratory protective equipment (RPE) available from rural community markets. However, scientific data regarding the pesticide filtration efficiency of RPE commonly worn by farmers is limited. Thus, this study aimed to investigate the efficiency of insecticide filtration of various RPE commonly worn by farmers in Thailand. The half facepiece respirator was used as a control to compare the results with other RPE. Ten types of RPE were selected for testing. The filtration efficiency of each RPE against insecticides was tested in a laboratory. The remarkable findings were that a surgical mask demonstrated the least filtration efficiency of all tested insecticides, with a range of 25.7-61.5%. The RPE available in rural markets of Thailand had a filtration efficiency within a range of 64.9-95.4%, whereas a half facepiece respirator was the most efficient in filtering insecticides, with a range of 96.5-98.9%. Therefore, our results suggest that the RPE most frequently worn by farmers may not provide adequate protection when compared with the respirator. However, considerations around RPE use in low-and middle-income countries and tropical climate conditions should be based on pesticide toxicity and practical use, ensuring balance between the risks from pesticide exposure and acceptance of PPE use.

13.
Int J Mol Sci ; 22(5)2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33807899

ABSTRACT

We aimed to evaluate the angiogenic capacity of CXCL2 and IL8 affecting human endothelial cells to clarify their potential role in glioblastoma (GBM) angiogenesis. Human GBM samples and controls were stained for proangiogenic factors. Survival curves and molecule correlations were obtained from the TCGA (The Cancer Genome Atlas) database. Moreover, proliferative, migratory and angiogenic activity of peripheral (HUVEC) and brain specific (HBMEC) primary human endothelial cells were investigated including blockage of CXCR2 signaling with SB225502. Gene expression analyses of angiogenic molecules from endothelial cells were performed. Overexpression of VEGF and CXCL2 was observed in GBM patients and associated with a survival disadvantage. Molecules of the VEGF pathway correlated but no relation for CXCR1/2 and CXCL2/IL8 was found. Interestingly, receptors of endothelial cells were not induced by addition of proangiogenic factors in vitro. Proliferation and migration of HUVEC were increased by VEGF, CXCL2 as well as IL8. Their sprouting was enhanced through VEGF and CXCL2, while IL8 showed no effect. In contrast, brain endothelial cells reacted to all proangiogenic molecules. Additionally, treatment with a CXCR2 antagonist led to reduced chemokinesis and sprouting of endothelial cells. We demonstrate the impact of CXCR2 signaling on endothelial cells supporting an impact of this pathway in angiogenesis of glioblastoma.

14.
Int J Mol Sci ; 22(5)2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33807902

ABSTRACT

Although physical exercise-induced autophagy activation has been considered a therapeutic target to enhance tissue health and extend lifespan, the effects of different exercise models on autophagy in specific metabolic tissues are not completely understood. This descriptive investigation compared the acute effects of endurance (END), exhaustive (ET), strength (ST), and concurrent (CC) physical exercise protocols on markers of autophagy, genes, and proteins in the gastrocnemius muscle, heart, and liver of mice. The animals were euthanized immediately (0 h) and six hours (6 h) after the acute exercise for the measurement of glycogen levels, mRNA expression of Prkaa1, Ppargc1a, Mtor, Ulk1, Becn1, Atg5, Map1lc3b, Sqstm1, and protein levels of Beclin 1 and ATG5. The markers of autophagy were measured by quantifying the protein levels of LC3II and Sqstm1/p62 in response to three consecutive days of intraperitoneal injections of colchicine. In summary, for gastrocnemius muscle samples, the main alterations in mRNA expressions were observed after 6 h and for the ST group, and the markers of autophagy for the CC group were increased (i.e., LC3II and Sqstm1/p62). In the heart, the Beclin 1 and ATG5 levels were downregulated for the ET group. Regarding the markers of autophagy, the Sqstm1/p62 in the heart tissue was upregulated for the END and ST groups, highlighting the beneficial effects of these exercise models. The liver protein levels of ATG5 were downregulated for the ET group. After the colchicine treatment, the liver protein levels of Sqstm1/p62 were decreased for the END and ET groups compared to the CT, ST, and CC groups. These results could be related to diabetes and obesity development or liver dysfunction improvement, demanding further investigations.

15.
Article in English | MEDLINE | ID: mdl-33807905

ABSTRACT

Inuit communities in the Circumpolar North have experienced a nutrition transition characterized by the decreased intake of culturally important, nutrient-rich traditional food (country food), and an increased intake of market food, resulting in concerns over reduced diet quality and emerging chronic diseases. Nutrition in early life is critical for development, may influence health risks in later life, and is an important concern for Inuit community health. The goal of this scoping review was to characterize the nature, extent, and range of the published literature on Inuit country food and health in pregnancy and childhood. A search string was developed and applied to three databases, followed by title and abstract screening and full text review. Articles published between 1995 and 2019 were included, and data were extracted and summarized descriptively. The number of articles generally increased over time, despite the unequal geographic distribution of articles. The majority of the articles focused on environmental contaminants, and one-quarter described nutrient adequacy. Few articles described food security or food safety in pregnancy, and the most utilized quantitative methods. Gaps in understanding of country food use in pregnancy and early childhood highlight areas of future research to support public health policy for this population. Given the critical role of good nutrition in early life and the important contribution country food makes to diet quality for Inuit, further understanding of this interface is warranted.

16.
Article in English | MEDLINE | ID: mdl-33807907

ABSTRACT

The current rapid growth of the economy has necessitated an assessment of health-related quality of life (HRQOL) and its associated factors among employees. Unfortunately, there are still limited data available in this area among the Malaysian working population in government sectors. The aim of this study was to evaluate the factors associated with HRQOL among government employees in Putrajaya, Malaysia. This cross-sectional study recruited 460 eligible government employees who worked in the area of Putrajaya through simple random sampling. The self-administered questionnaire was distributed to these participants to collect information on the SF-36 profile of scores, sociodemographic factors, lifestyle factors, and medical history. The results of this study signify that most of the participants were identified as having good HRQOL with the mean score of overall HRQOL was 72.42 ± 14.99. Multivariate analysis showed that being younger, receiving a better monthly personal income, a smaller household number, performing more physical activity, not having any chronic disease, and not using any long-term medication were significantly positively associated with overall HRQOL. The participants who did not have a family history of chronic disease were reported to be significantly associated with better mental component summary (MCS). Further, males were significantly positively associated with bodily pain (BP) and general health (GH) only, whereas better occupational status was limited to social functioning (SF). In conclusion, the results of this study provide motivation for future research and initiatives for improving the physical, emotional, and social well-being of government employees.

17.
Viruses ; 13(3)2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33807908

ABSTRACT

We evaluated a lyophilized CRISPR-Cas12 assay for SARS-CoV-2 detection (Lyo-CRISPR SARS-CoV-2 kit) based on reverse transcription, isothermal amplification, and CRISPR-Cas12 reaction. From a total of 210 RNA samples extracted from nasopharyngeal swabs using spin columns, the Lyo-CRISPR SARS-CoV-2 kit detected 105/105 (100%; 95% confidence interval (CI): 96.55-100) positive samples and 104/105 (99.05%; 95% CI: 94.81-99.97) negative samples that were previously tested using commercial RT-qPCR. The estimated overall Kappa index was 0.991, reflecting an almost perfect concordance level between the two diagnostic tests. An initial validation test was also performed on 30 nasopharyngeal samples collected in lysis buffer, in which the Lyo-CRISPR SARS-CoV-2 kit detected 20/21 (95.24%; 95% CI: 76.18-99.88) positive samples and 9/9 (100%; 95% CI: 66.37-100) negative samples. The estimated Kappa index was 0.923, indicating a strong concordance between the test procedures. The Lyo-CRISPR SARS-CoV-2 kit was suitable for detecting a wide range of RT-qPCR-positive samples (cycle threshold range: 11.45-36.90) and dilutions of heat-inactivated virus (range: 2.5-100 copies/µL); no cross-reaction was observed with the other respiratory pathogens tested. We demonstrated that the performance of the Lyo-CRISPR SARS-CoV-2 kit was similar to that of commercial RT-qPCR, as the former was highly sensitive and specific, timesaving (1.5 h), inexpensive, and did not require sophisticated equipment. The use of this kit would reduce the time taken for diagnosis and facilitate molecular diagnosis in low-resource laboratories.

18.
Article in English | MEDLINE | ID: mdl-33807910

ABSTRACT

Gross motor locomotion is the basis of various sensory motor locomotion. Interventions helping preschoolers develop gross motor skills (GMS) could provide a solid foundation for complex motor skills. This study analyzed a table tennis physical activity program's influence on preschoolers' GMS development with 104 preschoolers (experimental group (EG): N = 52, 25 boys, 27 girls; control group (CG): N = 52, 25 boys, 27 girls). The EG conducted table tennis physical activities three times per week for 12 weeks. Preschoolers' GMSs were assessed using the Test of Gross Motor Development (second edition). After 12 weeks, both the male and female EGs had significantly improved scores for GMS, locomotor subtest, gallop, hop, leap, slide, object control subtest, strike a stationary ball, stationary dribble, catch, overarm throw, and underhand roll (p < 0.05, p < 0.01, p < 0.001). The female EG also showed significant improvement for the run, horizontal jump, and catch in the post-test. Both the male and female EGs significantly outperformed the control group in their post-test scores for GMS, locomotor subtest, object control subtest, strike a stationary ball, overarm throw, and underhand roll (p < 0.05). The female EG also showed significant differences in slide scores (p < 0.05). Therefore, table tennis physical activities can promote preschoolers' GMS development, especially object control skills. The research results provide an empirical basis for preschoolers' physical education. Meanwhile, our findings have important implications for preschoolers' GMS development and table tennis' popularization in Chinese kindergartens.

19.
Cells ; 10(3)2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33807911

ABSTRACT

The evolution of anisogamy or gamete size dimorphism is a fundamental transition in evolutionary history, and it is the origin of the female and male sexes. Although mathematical models attempting to explain this transition have been published as early as 1932, the 1972 model of Parker, Baker, and Smith is considered to be the first explanation for the evolution of anisogamy that is consistent with modern evolutionary theory. The central idea of the model is ingenious in its simplicity: selection simultaneously favours large gametes for zygote provisioning, and small gametes for numerical competition, and under certain conditions the outcome is anisogamy. In this article, I derive novel analytical solutions to a 2002 game theoretical update of the 1972 anisogamy model, and use these solutions to examine its robustness to variation in its central assumptions. Combining new results with those from earlier papers, I find that the model is quite robust to variation in its central components. This kind of robustness is crucially important in a model for an early evolutionary transition where we may only have an approximate understanding of constraints that the different parts of the model must obey.

20.
Nutrients ; 13(3)2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33807914

ABSTRACT

Intestinal mucus protects epithelial and immune cells from the gut resident microorganisms, and provides growth-promoting factors as mucus-derived O-glycans for beneficial bacteria. A lack of intestinal protective mucus results in changes in the commensal microflora composition, mucosal immune system reprogramming, and inflammation. Previous work has shown that fucose, the terminal glycan chain component of the intestinal glycoprotein Mucin2, and fucoidan polysaccharides have an anti-inflammatory effect in some mouse models of colitis. This study evaluates the effect of fucose on reproductive performance in heterozygous mutant Muc2 female mice. We found that even though Muc2+/- females are physiologically indistinguishable from C57Bl/6 mice, they have a significantly reduced reproductive performance upon dietary fucose supplementation. Metagenomic analysis reveals that the otherwise healthy wild-type siblings of Muc2-/- animals have reduced numbers of some of the intestinal commensal bacterial species, compared to C57BL/6 mice. We propose that the changes in beneficial microflora affect the immune status in Muc2+/- mice, which causes implantation impairment. In accordance with this hypothesis, we find that macrophage polarization during pregnancy is impaired in Muc2+/- females upon addition of fucose. Metabolic profiling of peritoneal macrophages from Muc2+/- females reveals their predisposition towards anaerobic glycolysis in favor of oxidative phosphorylation, compared to C57BL/6-derived cells. In vitro experiments on phagocytosis activity and mitochondrial respiration suggest that fucose affects oxidative phosphorylation in a genotype-specific manner, which might interfere with implantation depending on the initial status of macrophages. This hypothesis is further confirmed in BALB/c female mice, where fucose caused pregnancy loss and opposed implantation-associated M2 macrophage polarization. Taken together, these data suggest that intestinal microflora affects host immunity and pregnancy outcome. At the same time, dietary fucose might act as a differential regulator of macrophage polarization during implantation, depending on the immune status of the host.

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