Targeted inhibition of allergen‐induced histamine production by neutrophils

Abstract Background Allergic asthma is an inflammatory disease resulting from continued or intermittent allergen exposure, and allergic rhinitis can be trigger of asthma. The main mechanism of these disease is allergic reaction and immune response dysregulation. Co-Q10 is an enzyme cofactor in mitochondria can control asthma and allergic rhinitis symptoms. In the present study, we determined that the CoQ10-induced anti-allergic effects were mediated by up-regulation of Nrf2. Methods Animal models of allergic rhinitis and allergic asthma were produced and treated with Co-Q10, Co-Q10 and O-3, Co-Q10 and Mg-S. Bronchoalveolar lavage fluid was collected from animal models, and IL-4, 5, 13, INF-y, Eicosanoids, IgE, EPO, and histamine production were measured. Also, COX-2, CCL24, CCL11, Nrf2, Eotaxin, Cytb, COX1 and ND1 genes expressions and histopathology were studied. BALf's cells were collected by tracheostomy and used in slide producing by cytospine. Cytokines, Eicosanoids, IgE, EPO, and histamine were measured by ELISA method. Gene expression was done by Real-time PCR. Results Co-Q10 with two supplementation (Mg-S and O-3) modulate MRC, BALf eosinophils, eosinophilic inflammation related genes (eotaxin, CCL11 and CCL24), peribronchial and perivascular inflammation, EPO, type 2 cytokines (IL-4, 5 and 13), IgE, histamine, Cyc-LT and LTB4 as main allergic bio-factors. Importantly, Co-Q10 treatment increased Nrf2 expression and Nrf2 induced antioxidant genes, glutathione redox and inhibited inflammation, oxidative stress injury, Th2 cytokines production and attenuated allergic inflammatory responses. Conclusion Nrf2 is activated in response to allergen, induces resistance against the rhinitis and asthma development and plays an essential role in broncho-protection. Co-Q10 increases the Nrf2 expression and the Nrf2 over-expression has strong effect in control of type2 cytokines, allergic mediators and inflammatory factors that lead to harnessing of allergy and asthma. Graphic abstract

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Targeted inhibition of GRP78 by HA15 promotes apoptosis of lung cancer cells accompanied by ER stress and autophagy

Biology Open ◽

10.1242/bio.053298 ◽

2020 ◽

Vol 9 (11) ◽

pp. bio053298

Author(s):

Jingjing Wu ◽

Youqile Wu ◽

Xuemei Lian

Keyword(s):

Lung Cancer ◽

Protein Expression ◽

Cell Viability ◽

Er Stress ◽

Cancer Cells ◽

Lung Tumor ◽

Lung Cancer Cells ◽

Dependent Manner ◽

Mice Model ◽

Targeted Inhibition

ABSTRACTThis study investigated the pathophysiological role of GRP78 in the survival of lung cancer cells. Lung cancer patient data from public databases were used to analyze the expression of GRP78 and its influence on prognoses. In vivo, GRP78 protein expression was analyzed in an established urethane-induced lung tumor mouse model. In vitro, the effects of targeted inhibition of GRP78 by HA15 in lung cancer cells were assessed, with cell viability analyzed using a CCK-8 assay, cell proliferation using an EdU assay, apoptosis and cell cycle using flow cytometry, subcellular structure using electron microscopy, and relative mRNA and protein expression using RT-PCR, western blotting or immunofluorescence assays. The results showed that GRP78 was highly expressed in the lung tissue of lung cancer mice model or patients, and was associated with a poor prognosis. After inhibition of GRP78 in lung cancer cells by HA15, cell viability was decreased in a dose- and time-dependent manner, proliferation was suppressed and apoptosis promoted. Unfolded protein response signaling pathway proteins were activated, and the autophagy-related proteins and mRNAs were upregulated. Therefore, targeted inhibition of GRP78 by HA15 promotes apoptosis of lung cancer cells accompanied by ER stress and autophagy.

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Characterization and Control of Erwinia spp. and Pluralibacter sp. in Tuna Salad Preparations

Journal of Food Protection ◽

10.4315/0362-028x.jfp-18-506 ◽

2019 ◽

Vol 82 (6) ◽

pp. 1071-1081

Author(s):

KRISTIN BJORNSDOTTIR-BUTLER ◽

SUSAN McCARTHY ◽

RONALD A. BENNER

Keyword(s):

Growth Conditions ◽

Whole Genome ◽

Processing Conditions ◽

Optimum Growth ◽

Significant Growth ◽

Ph Values ◽

Histamine Production ◽

Different Temperatures ◽

And Control ◽

Erwinia Persicina

ABSTRACT Histamine-producing Erwinia and Pluralibacter spp. capable of producing toxic histamine levels were isolated from ingredients commonly used in tuna salad preparations. The characterization and control of these histamine-producing bacteria are necessary to prevent illness from tuna salad consumption. We confirmed the identity of two Erwinia spp. and one Pluralibacter sp. previously isolated from tuna salad ingredients through whole genome sequencing and phylogenic analysis and characterized them for growth and histamine production at different temperatures, pH values, and salt concentrations. In addition, we examined the effects of dried vinegar (DV) powder on growth and histamine production of these strains in inoculated tuna salad preparations. Optimum growth temperatures in tryptic soy broth (TSB) for the two Erwinia spp. and one Pluralibacter sp. were 30.1, 31.1, and 33.9°C, respectively, and growth in TSB was observed at 5°C for both genera. Optimum histamine production of Erwinia persicina, Erwinia spp., and Pluralibacter spp. in TSB with histidine occurred from 25 to 30°C, pH 4 to 6, and 0 to 4% NaCl. No significant growth or histamine production was observed in tuna salad preparations stored at 4°C. Growth and histamine production by Erwinia or Pluralibacter spp. was inhibited in tuna salad containing celery and onion and 2% DV, whereas significant growth and histamine production occurred in tuna salad without DV. Understanding optimum growth conditions and histamine production can provide guidance to tuna salad manufacturers in formulating products and adjusting processing conditions that minimize hazards from these histamine-producing bacteria. Addition of 2% DV to tuna salad preparations may prevent histamine production in the event of temperature abuse. HIGHLIGHTS

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