Πέμπτη 25 Μαρτίου 2021

Regulatory effect of mitoQ on the mtROS-NLRP3 inflammasome pathway in leptin-pretreated BEAS-2 cells

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Exp Ther Med. 2021 May;21(5):466. doi: 10.3892/etm.2021.9897. Epub 2021 Mar 8.

ABSTRACT

Obese asthma is a phenotype of asthma whose occurrence is gradually increasing in both adults and children. The majority of studies have demonstrated that obesity is a major risk factor for asthma and the effect of obesity on the lungs is considerable. NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome has been previously demonstrated to serve a role in obese asthma mediated by mitochondrial reactive oxygen species (mtROS). The aim of the present in vitro study was to investigate the effect of leptin on airway epithelial cells and the protective effect of the mitochondrial-targeted antioxidant mitoquinone (mitoQ). Human normal bronchial epithelial cell lines BEAS-2 cells were used and divided into 6 groups: Control group (negative control), DMSO group (solvent control), lipopolysaccharide (LPS) group (positive control), LPS + mitoQ group, Leptin group and Leptin + mitoQ group. CCK8 assay was used to establish the optimal concentration and incubation time of the drugs. mitoTracker probe and mitoSOX reagent were used to detect the integrity of mitochondrial membranes and the content of mtROS. mRNA expression levels were detected by reverse transcription-quantitative PCR analysis. It was revealed that the mitochondrial membrane was disrupted in the Leptin group, which recovered after treatment with mitoQ. As a result, the production of mitochondrial reactive oxygen species (mtROS) in the Leptin group was significantly increased (P<0.01), but following treatment with mitoQ, this overproduction of mtROS was significantly decreased to normal levels (P<0.01). Furthermore, the expression levels of NOD-, LRR- and pyrin domain-containing protein 3 NLRP3 and caspase-1 mRNA in the leptin-pretreated BEAS-2 cells were significantly increased compared with those in the control group (P<0.01), while they wer e decreased following mitoQ treatment (P<0.01). Taken together, these data suggested that leptin may promote airway inflammation partially through upregulating the mtROS-NLRP3 inflammasome signaling pathway in airway epithelial cells and mitoQ may be a potential treatment for obese asthma.

PMID:33763153 | PMC:PMC7983181 | DOI:10.3892/etm.2021.9897

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Management of primary ciliary dyskinesia

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Via hno

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HNO. 2021 Mar 24. doi: 10.1007/s00106-021-01037-w. Online ahead of print.

NO ABSTRACT

PMID:33763740 | DOI:10.1007/s00106-021-01037-w

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Clinicopathological and immunohistochemical behavior of ductal carcinoma of the salivary and lacrimal gland in a Mexican Mestizo population

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Eur Arch Otorhinolaryngol. 2021 Mar 24. doi: 10.1007/s00405-021-06757-x. Online ahead of print.

ABSTRACT

PURPOSE: Salivary gland tumors are rare and include benign and malignant entities with different behavior and prognosis. Salivary gland carcinoma accounts for 0.2% of all cancers and 5-9% of head and neck carcinomas. We aim to describe the clinicopathological characteristics and discuss the immunohistochemical findings of salivary ductal carcinoma.

METHODS: We obtained 17 cases (2.3%) of salivary ductal carcinoma (SDC) from 727 patients with parotid tumors at our cancer center from a database covering a 22-year period (1996-2018). Two pathologists confirmed the diagnosis and excluded 6 cases. Eleven cases were assessed by immunohistochemistry (IHC) for HER2, estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), mammaglobin, P53, GATA3, S100, cytokeratins (7,8,14,18, and 20), P63, PAX8, calponin, and SOX10 .

RESULTS: Eleven SDC cases were in advanced stage, and 80% had metastasis. All cases were surgically treated, and 40% received different adjuvant chemotherapy regimens. we found that most patients were dead of disease. The histological and immunohistochemical analysis showed that 70% of cases were high-grade, 40% were positive for HER2, and 50% for AR. Moreover, a high Ki-67 proliferative index was detected in all cases. We observed luminal differentiation in 50% of cases.

CONCLUSION: SDC is a rare entity and survival is very poor. It is histologically similar to ductal carcinoma of the breast. However, important differences exist that help to distinguish them in case of synchronous cancers. The clinical behavior of SDC seems to be more aggressive and IHC analysis is useful for designing therapies.

PMID:33763743 | DOI:10.1007/s00405-021-06757-x

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Epicutaneously sensitized food‐induced anaphylaxis is ameliorated with “oral tolerance” to antigen

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Abstract

Food allergy is an antigen‐specific immunological adverse reaction after exposure to a given food. Multiple clinical studies showed that oral immunotherapy (OIT) is effective for the prevention and treatment for food allergy that is developed in infants and children. However, the effectiveness of OIT for epicutaneously sensitized food allergy remains unclear. Previously, we established a mouse model of epicutaneous‐sensitized food allergy. In this model, systemic allergic reaction including intestinal and skin symptoms, such as anaphylaxis, was observed. We treated this model with OIT in two ways (OIT before sensitization or OIT during the sensitization phase) and evaluated the preventive effect of both methods. OIT before sensitization significantly ameliorated mast cell degranulation in sensitized skin, but there was no decrease in rectal temperatures or in mast cell degranulation in the jejunum. However, OIT administered during the sensitization phase significantly ameliora ted the decrease in rectal temperature and mast cell degranulation in the skin and jejunum. OIT before sensitization increased the regulatory T cells in mesenteric lymph node (MLN), but not in the spleen, and it reduced antigen‐specific IgG, but not IgE, production compared with the non‐OIT control. However, OIT during sensitization caused a greater increase in regulatory T cells in both the MLN and spleen and reduced antigen‐specific IgE and IgG generation compared with the non‐OIT control group. Thus, OIT during the sensitization phase was effective for the prevention of epicutaneous‐sensitized food allergy.

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Serum S100A12 levels: Possible association with skin sclerosis and interstitial lung disease in systemic sclerosis

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Abstract

Damage‐associated molecular patterns (DAMPs) have drawn much attention as a member of disease‐associated molecules in systemic sclerosis (SSc). In this study, we investigated the potential contribution of S100A12, a member of DAMPs, to the development of SSc by evaluating S100A12 expression in the lesional skin and the clinical correlation of serum S100A12 levels. S100A12 expression was markedly elevated in the epidermis of SSc‐involved skin at protein levels and in the bulk skin at mRNA levels. The deficiency of transcription factor Fli1, a predisposing factor of SSc, enhanced S100A12 expression and Fli1 occupied the S100A12 promoter in normal human keratinocytes. Serum S100A12 levels were higher in SSc patients, especially in those with diffuse cutaneous involvement, than in healthy controls and positively correlated with skin score. Furthermore, the presence of interstitial lung disease significantly augmented serum levels of S100A12. Importantly, serum S100A12 lev els correlated inversely with both per cent forced vital capacity and per cent diffusing capacity for carbon monoxide and positively with serum levels of KL‐6 and surfactant protein‐D. Collectively, these results indicate a possible contribution of S100A12 to skin sclerosis and interstitial lung disease associated with SSc, further supporting the critical roles of DAMPs in the pathogenesis of this disease.

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The Clinical and Pathological Characteristics of Malignant Struma Ovarii: An Analysis of 144 Published Patients

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Front Oncol. 2021 Mar 5;11:645156. doi: 10.3389/fonc.2021.645156. eCollection 2021.

ABSTRACT

The objective of this study is to summarize the clinical and pathologic characteristics of malignant struma ovarii to facilitate the early diagnosis and treatment of this disease. All 144 patients were females from 27 countries. The mean age of the patients at diagnosis was 42.6 years. Overall, 35.71% of the patients underwent unilateral oophorectomy, 58.57% of the patients underwent bilateral oophorectomy, 5.72% of the patients were not ovariectomized, and 38.57% of the patients received radioactive iodine treatment with an average dose of 158.22 mCI each time. "Impure" types accounted for 70.19% of the cases, while pure types accounted for 29.81% of the cases. Among these cases, papillary thyroid carcinoma accounted for 50.00%, follicular thyroid carcinoma accounted for 26.47%, follicular variant of papillary thyroid carcinoma accounted for 18.63%, papillary and follicular mixed thyroid carcinoma accounted for 2.94%, anaplastic carcinoma accounted for 0.98%, and medullary carcinoma accounted for 0.98%. In total, 21 patients (51.22%) had elevated CA125. More than half of the patients (51.94%) had metastasis outside the ovary. The most common metastatic site was the pelvic cavity. The misdiagnosis rate was 17.27%. Mortality was related to metastasis and the cancer type. Gene mutations were found in the NRAS, KRAS, BRAF, and KIT genes and were similar to those in thyroid carcinoma, but some patients (37.5%) did not exhibit any gene mutations. Regardless of the treatment received, the survival rate is high. Treatment could initially include ovariectomy; however, in cases with metastasis and iodine uptake of the metastatic tumor, thyroidectomy, radioactive iodine therapy, and thyroid hormone inhibiting therapy are indicated.

PMID:33763376 | PMC:PMC7982850 | DOI:10.3389/fonc.2021.645156

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The PCOC Symptom Assessment Scale (SAS): A valid measure for daily use at point of care and in palliative care programs

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by Barbara A. Daveson, Samuel Frederic Allingham, Sabina Clapham, Claire E. Johnson, David C. Currow, Patsy Yates, Kathy Eagar

Background

Very few measures are used successfully as part of routine care within national palliative care outcome programs. Only a handful of studies examine these measures. The aim of this study is to evaluate the validity of a measure used in a national outcomes program: the Palliative Care Outcomes Collaboration Symptom Assessment Scale (PCOC SAS).

Methods

A retrospective multi-site cohort study with secondary analysis of routinely collected patient-level data to assess PCOC SAS's internal consistency, construct validity, reliability, interpretability, acceptability and sensitivity. The analyses used two sets, with data collected by inpatient and community palliative care services registered with the Australian national PCOC.

Results

Dataset one included 1,117 patients receiving palliative care from 21 services. Dataset two included 5,294 patients receiving palliative care from 119 PCOC services. PCOC SAS demonstrated the ability to detect and discriminate dist ress by palliative care phase, functional status and diagnosis. Excellent and good convergent and discriminant validity were demonstrated. Fair through to substantial inter-rater and intra-rater reliability levels were evidenced. Sufficient interpretability resulted along with necessary levels of acceptability and sensitivity.

Conclusion

PCOC SAS is a valid and reliable patient-reported outcome measure suitable for use in routine clinical care with patients requiring palliative and or end-of-life care, including in national outcomes programs.

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