Agonist of PPAR-γ Reduced Epithelial-Mesenchymal Transition in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps via Inhibition of High Mobility Group Box1.

Epithelial-mesenchymal transition (EMT) has been reported to occur in eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). Among the cytokines that cause EMT, high mobility group box 1 (HMGB1) has been shown to give rise to EMT in airway epithelial cells. However, the mechanism of HMGB1-induced EMT in ECRSwNP is unknown. We explored the mechanism and possible inhibitor. Immunohistochemistry (IHC), immunofluorescence (IF), and western blot assay were used to detect the expression and location of HMGB1, peroxisome proliferator-activated receptor-γ (PPAR-γ), and EMT markers in eighteen ECRSwNP and twelve normal nasal mucosa tissues. Epithelial cells isolated from ECRSwNP were cultured with various doses of recombinant human HMGB1 (rhHMGB1) to study the expression of PPAR-γ, and EMT markers. Additionally, the ligand of PPAR-γ was incubated with epithelial cells to interfere with the effects of lipopolysaccharide (LPS) or rhHMGB1 to explore the effect on expression of HMGB1 and EMT markers. These results suggest that HMGB1 was highly expressed in ECRSwNP compared with its expression in control tissues, and EMT was also found highly in ECRSwNP compared with control tissues. Moreover, the cytoplasmic accumulation of HMGB1 in ECRSwNP was obvious compared with normal tissues. We also found dose-dependent induction by rhHMGB1 of up-regulation of N-cadherin and vimentin and down-regulation of ZO-1 and E-cadherin in epithelial cells isolated from ECRSwNP. The agonist of PPAR-γ not only reduced release of HMGB1 induced by LPS, but also reversed the EMT. The protective role of PPAR-γ also appeared in cells that had been incubated with rhHMGB1. In the current study, we discovered that the agonist of PPAR-γ has a potential role in inhibited HMGB1-induced EMT in ECRSwNP. The agonist of PPAR-γ may contribute to inhabit epithelial cells to become mesenchymal-like cells which play an important role in the pathogenesis of ECRSwNP.

AIM2 inflammasome activation may mediate high mobility group box 1 release in murine allergic rhinitis.

INTRODUCTION: High mobility group box 1 protein participates in the pathogenesis of allergic rhinitis. Activation of the inflammasome can mediate the release of high mobility group box 1. The role of the absent in melanoma 2 inflammasome in allergic rhinitis remains unclear. OBJECTIVE: This study aimed to investigate the function of absent in melanoma 2 inflammasome in murine allergic rhinitis and the interaction between high mobility group box 1 and the absent in melanoma 2 inflammasome. METHODS: A murine allergic rhinitis model was established using twenty Balb/c mice. Expression of the components of the absent in melanoma 2 inflammasome: absent in melanoma 2, apoptosis-associated speck-like protein containing a CARD (Asc), caspase-1 p20, and additional nod-like receptor family pyrin domain containing 3 (Nlrp3) were detected by western blotting during allergic rhinitis. Alterations of absent in melanoma 2, caspase-1, and high mobility group box 1 after ovalbumin challenge were demonstrated by immunohistochemistry. TdT-mediated dUTP Nick end labeling, TUNEL assay, and cleavage of caspase-3 and PARP-1 were used for the observation of pyroptosis. RESULTS: Eosinophilia and goblet cell infiltration were observed in the nasal mucosa of mice in the allergic rhinitis group. Absent in melanoma 2, Asc, and caspase-1 p20 increased after ovalbumin exposure while Nlrp3 did not. High mobility group box 1 was released in the nasal mucosa of allergic rhinitis mice. TUNEL-positive cells increased in the epithelium and laminae propria, whereas cleavage of caspase-3 and PARP-1 was not observed. CONCLUSIONS: The absent in melanoma 2 inflammasome was activated and pyroptosis may occur in the nasal mucosa after ovalbumin treatment. These may contribute to the translocation of high mobility group box 1 and the development of allergic rhinitis.

Combined use of bacterial artificial chromosomes-on-beads with karyotype detection improves prenatal diagnosis.

BACKGROUND: This study evaluated the individual and combined diagnostic performance of the bacterial artificial chromosomes (BACs)-on-Beads (BoBs™) assay and conventional karyotyping for the prenatal detection of chromosomal abnormalities in pregnant women who were 35 or more years-old. METHOD: The primary outcome was concordance of any numerical, structural, or submicroscopic chromosomal abnormalities between BoBs™ and conventional karyotyping of amniotic fluid specimens from pregnant women at 17 to 22 weeks gestation. RESULTS: We examined samples from 4852 pregnant women. BoBs™ indicated that 4708 samples were normal (97.03%), and 144 were abnormal (2.97%); conventional karyotyping indicated that 4656 (95.96%) samples were normal and 196 (4.04%) were abnormal. The combined use of both methods indicated that 4633 of 4852 samples were normal (95.49%) and 219 of 4852 samples (4.51%) were abnormal. The kappa coefficient of the combined test was 0.70, indicating substantial consistency between BoBs™ and conventional karyotyping (95% CI = 0.65-0.76, P < 0.001). CONCLUSIONS: Our results indicate that the combined use of BoBs™ and conventional karyotyping detected more fetal abnormalities than either test alone.

PPAR-γ Ligand Inhibits Nasopharyngeal Carcinoma Cell Proliferation and Metastasis by Regulating E2F2.

PURPOSE: Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear hormone receptor with a key role in lipid metabolism. Previous studies have identified various roles of PPAR-γ in cell cycle progression, cellular proliferation, and tumor progression. However, no report has described a role for PPAR-γ in human nasopharyngeal carcinoma (NPC). Notably, some studies have reported a relationship between PPAR-γ and E2F transcription factor 2 (E2F2), which has been identified as a regulator of cell cycle, apoptosis, and the DNA damage response. Notably, E2F2 has also been reported to correlate with a poor prognosis in patients with various malignancies. METHODS: We used immunohistochemical (IHC) and western blot methods to evaluate PPAR-γ and E2F2 expression and function in nonkeratinizing NPC and nasopharyngitis (NPG) tissue samples, as well as western blotting and CCK8 analyses in the NPC cell lines, CNE1 and CNE2. RESULTS: We observed lower levels of PPAR-γ expression in nonkeratinizing NPC tissues compared with NPG tissues and determined an association between a low level of PPAR-γ expression with a more advanced tumor stage. Furthermore, strong E2F2 expression was detected in nonkeratinizing NPC tissues. We further demonstrated that rosiglitazone, a PPAR-γ agonist, reduced E2F2 expression and proliferation in NPC cell lines. CONCLUSIONS: Our study results revealed a novel role for the PPAR-γ-E2F2 pathway in controlling NPC cell proliferation and metastasis.

AIM2 inflammasome activation may mediate high mobility group box 1 release in murine allergic rhinitis / Ativação do inflamassoma AIM2 pode mediar a liberação da proteína do grupo Box-1 de alta mobilidade no modelo murino de rinite alérgica

Abstract Introduction: High mobility group box 1 protein participates in the pathogenesis of allergic rhinitis. Activation of the inflammasome can mediate the release of high mobility group box 1. The role of the absent in melanoma 2 inflammasome in allergic rhinitis remains unclear. Objective: This study aimed to investigate the function of absent in melanoma 2 inflammasome in murine allergic rhinitis and the interaction between high mobility group box 1 and the absent in melanoma 2 inflammasome. Methods: A murine allergic rhinitis model was established using twenty Balb/c mice. Expression of the components of the absent in melanoma 2 inflammasome: absent in melanoma 2, apoptosis-associated speck-like protein containing a CARD (Asc), caspase-1 p20, and additional nod-like receptor family pyrin domain containing 3 (Nlrp3) were detected by western blotting during allergic rhinitis. Alterations of absent in melanoma 2, caspase-1, and high mobility group box 1 after ovalbumin challenge were demonstrated by immunohistochemistry. TdT-mediated dUTP Nick end labeling, TUNEL assay, and cleavage of caspase-3 and PARP-1 were used for the observation of pyroptosis. Results: Eosinophilia and goblet cell infiltration were observed in the nasal mucosa of mice in the allergic rhinitis group. Absent in melanoma 2, Asc, and caspase-1 p20 increased after ovalbumin exposure while Nlrp3 did not. High mobility group box 1 was released in the nasal mucosa of allergic rhinitis mice. TUNEL-positive cells increased in the epithelium and laminae propria, whereas cleavage of caspase-3 and PARP-1 was not observed. Conclusions: The absent in melanoma 2 inflammasome was activated and pyroptosis may occur in the nasal mucosa after ovalbumin treatment. These may contribute to the translocation of high mobility group box 1 and the development of allergic rhinitis.

Resumo Introdução: A proteína do grupo Box-1 de alta mobilidade participa da patogênese da rinite alérgica. A ativação do inflamassoma pode mediar a liberação de proteína do grupo Box-1 de alta mobilidade. O papel do inflamassoma ausente no melanoma 2 na rinite alérgica permanece incerto. Objetivo: Investigar a função do inflamassoma ausente no melanoma 2 em um modelo murino de rinite alérgica e a interação entre a proteína do grupo Box-1 de alta mobilidade e o inflamassoma ausente no melanoma 2. Método: Um modelo murino de rinite alérgica foi estabelecido com 20 camundongos Balb/c. A expressão dos componentes do inflamassoma ausente no melanoma 2, da proteína speck-like associada à apoptose com CARD (Asc), da caspase-1 p20 e do domínio de pirina da família NLR adicional com 3 (Nlrp3) foi detectada por western blotting durante a rinite alérgica. Alterações de inflamassoma ausente no melanoma 2, na caspase-1 e na proteína do grupo Box-1 de alta mobilidade após o teste de provocação com ovalbumina foram demonstradas por imuno-histoquímica. O ensaio dUTP Nick-End Labeling mediado por TdT, TUNEL e clivagem de caspase-3 e PARP-1 foram usados para a observação de piroptose. Resultados: Eosinofilia e infiltração de células caliciformes foram observadas na mucosa nasal de camundongos do grupo rinite alérgica. Inflamassoma ausente no melanoma 2, Asc e caspase-1 p20 aumentou após a exposição à ovalbumina, enquanto Nlrp3 não aumentou. A proteína do grupo Box-1 de alta mobilidade foi liberada na mucosa nasal de camundongos com rinite alérgica. As células TUNEL-positivas aumentaram no epitélio e na lâmina própria, enquanto a clivagem da caspase-3 e a PARP-1 não foram observadas. Conclusão: O inflamassoma ausente no melanoma 2 foi ativado e pode ocorrer piroptose na mucosa nasal após o tratamento com ovalbumina. Esses fatores podem contribuir para a translocação de proteína do grupo Box-1 de alta mobilidade e o desenvolvimento de rinite alérgica.