Infliximab modifies CD74-mediated lymphatic abnormalities and adipose tissue alterations in creeping fat of Crohn's disease.

BACKGROUND: Lymphatic abnormalities are essential for pathophysiologic changes of creeping fat (CrF) in Crohn's disease (CD). Anti-tumor necrosis factor (TNF) therapy has been proved to alleviate CrF lesions, however, whether it achieves these by remodeling lymphatics is unknown. METHODS: CD74 expression was detected in CrF and uninvolved mesentery of CD patients. Lymphatic functions in vitro were evaluated and lymphatic endothelium barrier were checked by transendothelial electrical resistance (TEER) and FITC-Dextran permeability. Protein level of tight junction and signaling pathways were detected by western blotting. RESULTS: CD74 was upregulated in LECs of CrF and positively correlated with TNF-α synthesis. This was suppressed by IFX administration. In vitro, TNF-α stimulated LECs to express CD74 through NF-κB signaling pathway, and this was rescued by IFX. CD74 downregulation suppressed the abilities of LECs in proliferation, migration and tube formation. Interaction of CD74-MIF impaired LECs' barrier via reducing tight junction proteins in an ERK1/2-dependent manner, which was reversed by CD74 downregulation. Consistently, the CD patients receiving IFX therapy displayed decreased lymphangiogenesis and improved mesenteric lymphatic endothelium barrier, companied with reduced adipocyte size and adipokine levels in CrF. CONCLUSIONS: Anti-TNF therapy could modify pathological changes in CrF by alleviating CD74-mediated lymphatic abnormalities.

Recent Advances in Development of Metal-Organic Frameworks Based Extraction Approaches for Food and Biological Matrices.

Food and human biological samples analysis are of great importance for human health. However, due to the complexity of sample matrices and low concentrations of target analytes, sample preparation is essentially critical for these samples through the whole analytical workflow. Metal-organic frameworks (MOFs), a class of synthesized functional nanomaterial, have been well recognized as novel adsorbents to enhance the sensitivity of current analytical methods and greatly assist the determination of potentially harmful substances present in food and biological samples. This critical review summarized the most advances in the applications of MOFs or hybrid MOFs as adsorbents for food and biological analysis in the past five years, particularly pertaining to sample preparation purpose including removal, adsorption, and enrichment of environmental contaminants. The synthetic routes and analytical performance of representative MOFs or MOFs composites are discussed. The limitations in preparation and application of reported MOFs adsorbents are discussed and the improvement methods for these limitations also have been concluded in the future perspectives.

Per- and polyfluoroalkyl substances exposure and its influence on the intestinal barrier: An overview on the advances.

Per- and polyfluoroalkyl substances (PFAS) are a class of artificially synthetic organic compounds that are hardly degraded in the natural environment. PFAS have been widely used for many decades, and the persistence and potential toxicity of PFAS are an emerging concern in the world. PFAS exposed via diet can be readily absorbed by the intestine and enter the circulatory system or accumulate directly at intestinal sites, which could interact with the intestine and cause the destruction of intestinal barrier. This review summarizes current relationships between PFAS exposure and intestinal barrier damage with a focus on more recent toxicological studies. Exposure to PFAS could cause inflammation in the gut, destruction of the gut epithelium and tight junction structure, reduction of the mucus layer, and induction of the toxicity of immune cells. PFAS accumulation could also induce microbial disorders and metabolic products changes. In addition, there are limited studies currently, and most available studies converge on the health risk of PFAS exposure for human intestinal disease. Therefore, more efforts are deserved to further understand potential associations between PFAS exposure and intestinal dysfunction and enable better assessment of exposomic toxicology and health risks for humans in the future.

Occurrence of Perfluoroalkyl and Polyfluoroalkyl Substances in Ice Cream, Instant Noodles, and Bubble Tea.

Food consumption is a significant exposure route to perfluoroalkyl and polyfluoroalkyl substances (PFAS). The concentrations of 27 PFAS in fast food were determined by ultrahigh-performance liquid chromatography-high resolution mass spectrometry. In ice cream, instant noodles, and bubble tea, some PFAS were detected, among which perfluorooctanoic acid, perfluoro-n-butanoic acid, and 6:2 polyfluoroalkyl phosphate monoester showed relatively high concentrations. PFAS migrating from bubble tea cups to the food simulant of 50% ethanol aqueous solution showed a difference compared with those migrating into bubble tea matrices. The migration of 27 PFAS to bubble tea samples indicated that long storage time increased PFAS levels (up to 4.8 times) and so did high storage temperature (up to 7.3 times). The hazard ratio, defined as the ratio of the estimated daily intake and the reference dose, was calculated, and it suggests that the total PFAS exposure risk due to consumption of bubble tea should be of concern.

Electrospun UiO-66-F4/polyacrylonitrile nanofibers for efficient extraction of perfluoroalkyl and polyfluoroalkyl substances in environmental media.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are a family of emerging contaminants which are widely present in environment. In this work, novel UiO-66-F4/polyacrylonitrile (UiO-66-F4/PAN) hybrid nanofibers were firstly prepared via blend electrospinning or in-situ growth method for the pipette-tip solid phase extraction of PFASs. Characterizations demonstrate the as-synthesized UiO-66-F4/PAN nanofibers have good chemical and thermal stability, possess large surface area (248 m²/g) and mesoporous framework structure. Several extraction factors including the amount of adsorbent, pH and ionic strength of sample solution, extraction time and eluent were investigated and the optimum conditions are 20 mg of the selected sorbent, adjusting to pH 5 and adding 4% w/v NaCl to sample solution, extraction for 12 min (3 min × 4). The good adsorption affinity of UiO-66-F4/PAN for PFASs can be attributed to the extensive adsorption sites and multiple interactions including hydrophobic interaction, hydrogen bonding and F-F interaction. Low limit of detection (0.008-0.076 µg/L), limit of quantification (0.010-0.163 µg/L) and recoveries (70.84-113.57%) for 9 PFASs with relative standard deviations < 15% were achieved. When applied in the analysis of target PFASs in lake water, tap water, beverage, and shrimp muscle samples, this method could achieve robust and accurate results with sufficient sensitivity for nine PFASs.

Effects of exposure to per- and polyfluoroalkyl substances on vaccine antibodies: A systematic review and meta-analysis based on epidemiological studies.

Vaccines are essential for children to defend against infection. Per- and polyfluoroalkyl substances (PFAS) are emerging contaminants with the characteristics of persistence and bioaccumulation. PFAS exposure can affect the function of the nervous, endocrine, and immune system of animals and humans. We aimed to conduct a systematic review and meta-analysis of the epidemiological studies investigating potential relationships between PFAS exposure and vaccine antibody levels, and assessed whether PFAS would affect vaccine response in healthy children. A literature search was conducted in PubMed, Web of Science, and Scopus databases up to February 2022. We chose studies that measured serum vaccines antibodies and PFAS concentrations of the participants. Essential information, including mean difference of percentage change, regression coefficient, odds ratio, Spearman correlation coefficient, and 95% confidence intervals, were extracted from the selected studies to conduct descriptive analysis and meta-analysis where appropriate. The qualities of these studies were evaluated as well. Finally, nine epidemiological studies about children met our inclusion criteria. A high degree of heterogeneity is observed in terms of breastfeeding time, confounder control, and detection method. Exposure to perfluorooctanoic acid and perfluorohexane sulfonic acid is negatively associated with tetanus antibody level in children without heterogeneity by Cochran's Q test (p = 0.26; p = 0.55), and exposure to perfluorohexane sulfonate is negatively associated with tetanus antibody level but with heterogeneity (p = 0.04). This comprehensive review suggests that PFAS can have adverse health effects on children by hindering the production of vaccine antibodies. There are some consistent and negative associations between children exposure to certain PFAS and tetanus antibody level. The association of the other four vaccines (measles, rubella, mumps, and influenza) with PFAS remains uncertain, because very few studies are available. Further studies are needed to validate the possible associations.

Association between maternal exposure to perfluoroalkyl and polyfluoroalkyl substances and risks of adverse pregnancy outcomes: A systematic review and meta-analysis.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs), a class of persistent endocrine-disrupting chemicals, are widely used in consumer products due to their unique amphiphilic properties. Previous epidemiological studies suggest association of maternal PFASs exposure and adverse pregnancy outcomes, while evidences about the association are inconsistent. The aim of this systematic review and meta-analysis is to assess the relationship of maternal PFASs exposure and adverse pregnancy outcomes. Twenty-one relevant studies were identified from three databases before 2020. The quality, heterogeneity and possibility of publication bias of included studies were evaluated by Newcastle-Ottawa Scale, Q-statistic and Begg's test, respectively. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were obtained by means of random-effects meta-analysis models. Meta-analysis results revealed that maternal exposure to perfluorooctane sulfonic acid (PFOS) may have a positive association with preterm birth (OR = 1.20, 95% CI: 1.04, 1.38). The pooled estimates also showed limited evidence of association between maternal perfluorononanoic acid (PFNA) exposure and miscarriage (OR = 1.48, 95% CI: 0.92, 2.38) with obvious heterogeneity (I2 = 93.9, p < 0.01). However, no such significant associations were found between the other PFASs and miscarriage, stillbirth and preterm birth. In addition, the subgroup analyses showed that studies on the relationship of maternal PFASs exposure and miscarriage were mainly contributed by developed countries. The meta-analysis results indicated maternal exposure to PFOS can increase the risk of preterm birth. The results of the included studies are inconsistent and the effects of PFASs on human health are complex. Further studies with enough samples are required to verify these findings.

Exposure to perfluoroalkyl substances and allergic outcomes in children: A systematic review and meta-analysis.

BACKGROUND: Perfluoroalkyl substances (PFASs) are persistent organic pollutants and widespread throughout the environment. Although exposure to PFASs may contribute to the development of allergic diseases in children, evidence about this association remains inconclusive. OBJECTIVE: To conduct a systematic review and meta-analysis to assess the association between PFASs exposure and allergic diseases in children based on current evidence. METHODS: The databases including PubMed, EMBASE, and Web of Science were searched to identify all observational studies that examined the association between PFASs exposure and the risk of childhood allergic diseases. The Newcastle-Ottawa Scale was used to evaluate the quality of case-crossover studies, and a previously validated quality assessment framework was used for observational studies lacking control groups. Random-effects meta-analysis models were applied to pool odds ratio (OR) with 95% confidence intervals (CIs). RESULTS: From an initial 94 articles (after duplicate removal), 13 studies through full-text assessment were included for quantitative assessment and descriptive synthesis. They are ten cohort studies, two cross-sectional studies, and one case-control study. The pooled estimates showed that perfluorononanoic acid (PFNA) was associated with eczema (OR = 0.89, 95% CI = 0.80-0.99), perfluorooctanesulfonic acid (PFOS) with atopic dermatitis (OR = 1.26, 95% CI = 1.01-1.58), and perfluorooctanoic acid (PFOA) with allergic rhinitis (OR = 1.33, 95% CI = 1.13-1.56). However, no such significant associations were found for wheeze and asthma. CONCLUSIONS: The meta-analysis results suggest that PFASs exposure could potentially be associated with eczema, atopic dermatitis, and allergic rhinitis during childhood, but not with childhood asthma or wheeze. Future studies are needed to verify these findings.