Objective-To define the pattern of mRNA expression of all human matrix metalloproteinases (MMPs) described to date in rheumatoid arthritis (RA) and traumatic synovial membrane, in order to diVerentiate between a physiological tissue remodelling pattern and that associated with inflammatory tissue destruction. Methods-Analysis

IFN-gamma rapidly primes the macrophage via JAK1/2-STAT1 pathway so that it can subsequently undergo a slower classical type 1 activation upon exposure to T helper (Th)1 cytokines such as IFNgamma or other activators, including tumor necrosis factor and lipopolysaccharide, e.g. in intracellular killing of phagocytosed Mycobacterium tuberculosis. If instead it is driven by Th2 cytokines interleukin (IL)-4 and IL-13, it undergoes alternate type 2 activation, which enhances endocytotic antigen uptake and presentation, mast cell and eosinophil involvement and type 2 granuloma formation, e.g. in response to parasitic and extracellular pathogens. Particle-induced macrophage activation was shown to differ from classical and alternate activation, showing in DNA microarray experiments (complete linkage/ Euclidean distance metric analysis) upregulation of nonsecreted structural/signaling molecules and lack of secreted proinflammatory cyto- and chemokines. The switch-off (deactivation) of already activated macrophages is an active, controlled process in which IL-10 and corticosteroids play important roles and to which 15dPGJ2, PGA1/2 and vasoactive intestinal peptide often contribute.

Persistent organic pollutants (POPs) have been associated with a wide range of adverse health effects. Our case-control study was performed to explore the association between placental levels of selected POPs and risks for neural tube defects (NTDs) in a Chinese population with a high prevalence of NTDs. Cases included 80 fetuses or newborns with NTDs, whereas the controls were 50 healthy, nonmalformed newborn infants. Placental concentrations of polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers were analyzed by gas chromatography-mass spectrometry. The medians of PAHs, o,p′-isomers of dichlorodiphenyltrichloroethane (DDT) and metabolites, α-and γ-hexachlorocyclohexane (HCH), and α-endosulfan were significantly higher in case placentas than in controls. PAH concentrations above the median were associated with a 4.52-fold [95% confidence interval (CI), 2.10-9.74) increased risk for any NTDs, and 5.84-(95% CI, 2.28-14.96) and 3.71-fold (95% CI, 1.57-8.79) increased risks for anencephaly and spina bifida, respectively. A dose-response relationship was observed between PAH levels and the risk of NTDs, with odds ratios for the second, third, and fourth quartiles, compared with the first, of 1.77-(95% CI, 0.66-4.76), 3.83-(95% CI, 1.37-10.75), and 11.67-fold (95% CI, 3.28-41.49), respectively. A dose-response relationship was observed for anencephaly and spina bifida subtypes. Similar results were observed for o,p′-DDT and metabolites, α-HCH, γ-HCH, and α-endosulfan, whereas no dose-response relationship was observed for the last two pollutants. Elevated placental concentrations of PAHs, o,p′-DDT and metabolites, and α-HCH were associated with increased risks of NTDs in this population.congenital abnormalities | indoor air pollution

Background Eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) display distinct patterns of inflammation. However, the pathogenic mechanisms underlying the heterogeneity of CRSwNP need further investigation. Objective To investigate local immunoglobulin E (IgE) production and phenotype of mast cells in eosinophilic and non-eosinophilic CRSwNP in Chinese. Methods Total and specific IgE levels were analyzed by means of the ImmunoCAP system. The molecular steps involved in class switch recombination to IgE were investigated using RT-PCR assays. Mast cell phenotypes, IgE- and high affinity IgE receptor (FcεRI)-positive cells, and allergen binding to specific IgE in sinonasal mucosa were determined by means of immunohistochemistry. Results Compared with controls and non-eosinophilic CRSwNP, local total IgE levels were increased, and local specific IgE to common aeroallergens was more frequently found, in Chinese eosinophilic CRSwNP independent of atopy and without significant association with Staphylococcus aureus enterotoxins. The ε germline gene transcript was also more frequently detected in eosinophilic CRSwNP. The number of IgE- and FcεRI-positive cells was increased in eosinophilic CRSwNP. Most IgE- and FcεRI-positive cells were mast cells. Dust mite antigens could bind to IgE on mast cells in situ. The number of mast cells positive for both tryptase and chymase and activated mast cells was increased in eosinophilic CRSwNP and the number of activated mast cells positively correlated with local IgE level, eotaxin-1 level, and eosinophil count in CRSwNP. Conclusions and Clinical Relevance The local IgE induced by common aeroallergens may mediate mast cell activation and contribute to subsequent eosinophilic inflammation in Chinese CRSwNP. This study offers a rationale for considering intervention strategies designed to target “local allergy” in eosinophilic CRSwNP.

• The concentration of heavy metals and metalloids in environment and children's blood are observed around the Chinese largest coking plant.• The health risk assessments of children are analyzed.• Foods from the coking plant are heavily contaminated by As, Cr and Se.• Food Ingestion pathway contributes most to children's average daily dose for most heavy metals and metalloids.• Higher potentially non-carcinogenic and carcinogenic risks happen to the local children. a b s t r a c t a r t i c l e i n f o Coking influences environmental quality and poses high risks to human health as large amounts of heavy metals and metalloids are emitted into the environment from coal during the coking process. Health risks depend heavily on multi-pathway and element-specific exposures, which have, unfortunately, been rarely studied. In this study, children's health risks and exposure levels to As, Se, and heavy metals (Pb, Cd, Cr, Ni, Co, Zn, Cu, Mn, V and Sb) in the water, soil, dust, air and locally produced food were studied based on field sampling and questionnaire-based surveys around the largest coking area in China. Human blood samples were collected and analyzed to indicate the exposure levels. The non-carcinogenic risks to children mainly resulted from Cr, Mn, Pb, As and Sb, the levels of which were 3 to 10 times higher than the acceptable levels (1.0 × 10 −6 ). The carcinogenic risks to children were 30 to 200 times higher than the safe level (1.0 × 10 −6 -1.0 × 10 −4 ), which could be attributed to Cr, As and Ni pollution. The estimated risks mainly came from the pathway involving the ingestion of locally produced food, accounting for more than 85% in total for most elements. For As, the food ingestion and air inhalation exposure pathways both contributed approximately 50%, respectively. The high risks in this study highlight the attention paid to the health of children who live in the vicinity of coking activities and the importance of site-specific multi-pathway health risk assessments and food safety to protect potentially exposed children.

Background The impacts of chronic airway diseases on coronavirus disease 2019 (COVID‐19) are far from understood. Objective To explore the influence of asthma and chronic obstructive pulmonary disease (COPD) comorbidity on disease expression and outcomes, and the potential underlying mechanisms in COVID‐19 patients. Methods A total of 961 hospitalized COVID‐19 patients with a definite clinical outcome (death or discharge) were retrospectively enrolled. Demographic and clinical information were extracted from the medical records. Lung tissue sections from patients suffering from lung cancer were used for immunohistochemistry study of angiotensin‐converting enzyme II (ACE2) expression. BEAS‐2B cell line was stimulated with various cytokines. Results In this cohort, 21 subjects (2.2%) had COPD and 22 (2.3%) had asthma. After adjusting for confounding factors, COPD patients had higher risk of developing severe illness (OR: 23.433; 95% CI 1.525‐360.135; P < .01) and acute respiratory distress syndrome (OR: 19.762; 95% CI 1.461‐267.369; P = .025) than asthmatics. COPD patients, particularly those with severe COVID‐19, had lower counts of CD4+ T and CD8+ T cells and B cells and higher levels of TNF‐α, IL‐2 receptor, IL‐10, IL‐8, and IL‐6 than asthmatics. COPD patients had increased, whereas asthmatics had decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. IL‐4 and IL‐13 downregulated, but TNF‐α, IL‐12, and IL‐17A upregulated ACE2 expression in BEAS‐2B cells. Conclusion Patients with asthma and COPD likely have different risk of severe COVID‐19, which may be associated with different ACE2 expression.

Distinct subsets of lesional DCs were found in eosinophilic and noneosinophilic CRSwNP, where OX40L/PD-L1(+) lesional DCs in eosinophilic CRSwNP could prime Th2 cells, whereas the low OX40L/PD-L1-expressing lesional DCs in noneosinophilic CRSwNP primarily induced Th1/Th17 cells.

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