Outer membrane protein a of Salmonella enterica serovar Typhimurium activates dendritic cells and enhances Th1 polarization

<p>Abstract</p> <p>Background</p> <p>Typhoid, which is caused by <it>Salmonella enterica </it>serovar Typhimurium, remains a major health concern worldwide. Multidrug-resistant strains of <it>Salmonella </it>have emerged which exhibit increased survivability and virulence, thus leading to increased morbidity. However, little is known about the protective immune response against this microorganism. The outer membrane protein (Omp)A of bacteria plays an important role in pathogenesis.</p> <p>Results</p> <p>We purified OmpA from <it>S. enterica </it>serovar Typhimurium (OmpA-sal) and characterized the role of OmpA-sal in promoting adaptive and innate immune responses. OmpA-sal functionally activated bone marrow-derived dendritic cells by augmenting expression of CD80, CD86, and major histocompatibility complex classes I and II. Interestingly, OmpA-sal induced production of interferon-γ from T cells in mixed lymphocyte reactions, thus indicating Th1-polarizing capacity. The expression of surface markers and cytokine production in dendritic cells was mediated by the TLR4 signaling pathway in a TLR4 Knock-out system.</p> <p>Conclusions</p> <p>Our findings suggest that OmpA-sal modulates the adaptive immune responses to <it>S. enterica </it>serovar Typhimurium by activating dendritic cells and driving Th1 polarization, which are important properties to consider in the development of effective <it>S. enterica </it>serovar Typhimurium vaccines and immunotherapy adjuvant.</p

Protective Effect of the Fruit Hull of Gleditsia sinensis on LPS-Induced Acute Lung Injury Is Associated with Nrf2 Activation

The fruit hull of Gleditsia sinensis (FGS) has been prescribed as a traditional eastern Asian medicinal remedy for the treatment of various respiratory diseases, but the efficacy and underlying mechanisms remain poorly characterized. Here, we explored a potential usage of FGS for the treatment of acute lung injury (ALI), a highly fatal inflammatory lung disease that urgently needs effective therapeutics, and investigated a mechanism for the anti-inflammatory activity of FGS. Pretreatment of C57BL/6 mice with FGS significantly attenuated LPS-induced neutrophilic lung inflammation compared to sham-treated, inflamed mice. Reporter assays, semiquantitative RT-PCR, and Western blot analyses show that while not affecting NF-κB, FGS activated Nrf2 and expressed Nrf2-regulated genes including GCLC, NQO-1, and HO-1 in RAW 264.7 cells. Furthermore, pretreatment of mice with FGS enhanced the expression of GCLC and HO-1 but suppressed that of proinflammatory cytokines in including TNF-α and IL-1β in the inflamed lungs. These results suggest that FGS effectively suppresses neutrophilic lung inflammation, which can be associated with, at least in part, FGS-activating anti-inflammatory factor Nrf2. Our results suggest that FGS can be developed as a therapeutic option for the treatment of ALI

Magnetic Resonance Imaging Features of Normal Thyroid Parenchyma and Incidental Diffuse Thyroid Disease: A Single-Center Study

Background: No previous studies have investigated the feasibility of magnetic resonance imaging (MRI) diagnosis for detecting incidental diffuse thyroid disease (DTD). This study investigated MRI features of normal thyroid parenchyma and incidental DTD.Methods: From January 2008 to December 2017, 387 patients underwent neck MRI in our hospital due to tumor/nodal staging (n = 137), lymphadenopathy (n = 122), inflammatory neck lesion (n = 85), congenital neck lesion (n = 12), and patient request (n = 31). Among them, 375 patients were excluded because of a lack of appropriate histopathological data on the thyroid parenchyma.Results: Among the patients included, 10 had normal thyroid parenchyma, 1 had Hashimoto thyroiditis, and 1 had diffuse hyperplasia. The common MRI features of normal thyroid parenchyma include iso-/slightly high and homogeneous signal intensity on T1/T2-weighted images, normal anteroposterior diameter of the thyroid gland, smooth margin, and homogeneously increased enhancement as compared to adjacent muscle. Hashimoto thyroiditis exhibited high and inhomogeneous signal intensity on T2-weighted images, while diffuse hyperplasia revealed an increased anteroposterior diameter and lobulated margin of the thyroid gland, and inhomogeneous enhancement.Conclusions: MRI may be helpful for detection of incidental DTD

Comparison of Postoperative Neck Pain and Discomfort, Swallowing Difficulty, and Voice Change After Conventional Open, Endoscopic, and Robotic Thyroidectomy: A Single-Center Cohort Study

Background: The objective of this study was to compare the postoperative neck pain and discomfort, swallowing difficulty, and voice change after conventional open thyroidectomy (COT), endoscopic thyroidectomy (ET), or robotic thyroidectomy (RT) performed by a single surgeon.Methods: From January 2013 to December 2017, 254 patients underwent COT, ET, or RT performed by a single surgeon and completed a postoperative symptom survey conducted in the outpatient clinic by three nurses. The survey collected information on postoperative neck pain and discomfort, swallowing difficulty, and voice change.Results: Of the 254 patients, 169 underwent COT, 32 underwent ET, and 53 underwent RT. The mean age in the COT, ET, and RT groups was 50.1, 44.5, and 41.6 years, respectively. The mean interval between thyroidectomy and survey in the COT, ET, and RT groups was 42.7, 50.2, and 9.2 months, respectively. Postoperative neck pain was significantly higher in the ET and RT groups than in the COT group (p = 0.026). The average neck impairment index score in the RT group was significantly higher than that in the COT group (p &lt; 0.001). There were no significant differences in pain scale scores, swallowing difficulty, swallowing impairment index, voice change, and voice hand index among the three groups.Conclusions: There were no significant differences in postoperative voice change or swallowing difficulty among the COT, ET, and RT groups, whereas neck pain and discomfort were more common after ET and RT than COT

Clinical implications of the BRAF mutation in papillary thyroid carcinoma and chronic lymphocytic thyroiditis

Abstract Background The purpose of this study was to examine the possible prognostics and clinicopathologic characteristics underlying the BRAFV600E mutation and papillary thyroid carcinoma (PTC) coexisting or in absence of chronic lymphocytic thyroiditis (CLT). Methods This study was conducted on 172 patients who had undergone total thyroidectomy or unilateral total thyroidectomy for PTC; the patients were then examined for the BRAFV600E mutation using specimens obtained after their surgery from January 2013 to August 2015. Results BRAF mutations were found in 130 of 172 patients (75.6%). CLT was present in 27.9% of patients (48/172). The incidence of the BRAFV600E mutation was significantly increased in the group with no CLT (P = 0.001). The findings of the multivariate analysis pertaining to the coexistence of CLT and PTC showed no significant correlation other than the BRAFV600E mutation. No significant difference was noted in the clinicopathologic factors between the two groups based on the coexistence of CLT in univariate and multivariate analyses. Conclusions The BRAFV600E mutation is less frequent in PTC coexisting with CLT presumably because CLT and the BRAFV600E mutation operate independently in the formation and progression of thyroid cancer

The Effect of Levothyroxine Discontinuation Timing on Postoperative Hypothyroidism after Hemithyroidectomy for Papillary Thyroid Microcarcinoma

Objective. No previous studies regarding the appropriate timing of thyroid hormone discontinuation after hemithyroidectomy have been published. This study aimed to identify the appropriate timing for levothyroxine discontinuation after hemithyroidectomy among patients with papillary thyroid microcarcinoma (PTMC). Methods. This study retrospectively evaluated 304 patients who underwent ≥1 attempt to discontinue levothyroxine after hemithyroidectomy for treating PTMC between January 2008 and December 2013. Fifty-three patients were excluded because of preoperative hypothyroidism or hyperthyroidism, a history of thyroid hormone or antithyroid therapy, no available serological data, or a postoperative follow-up of <24 months. We evaluated the associations of successful levothyroxine discontinuation with patient age, sex, preoperative serological data, underlying thyroid gland histopathology, anteroposterior diameter of the residual thyroid gland, number of discontinuation attempts, and initial discontinuation timing. Results. Among the 251 included patients, 125 patients (49.8%) achieved successful levothyroxine discontinuation during the follow-up period after hemithyroidectomy. There was a significant difference in the outcomes for patients who underwent an initial discontinuation attempt at ≤3 months and ≥4 months after hemithyroidectomy (p < 0.001). There were significant differences in the discontinuation outcomes according to underlying thyroid histopathology (p = 0.001), preoperative thyroid-stimulating hormone levels (p < 0.001), and number of discontinuation attempts (p < 0.001). Conclusions. Among patients with PTMC, the initial levothyroxine discontinuation attempt is recommended at ≥4 months after hemithyroidectomy

Ultrasonographic Features of Papillary Thyroid Carcinomas According to Their Subtypes

BackgroundThe ultrasonographic characteristics and difference for various subtypes of papillary thyroid carcinoma (PTC) are still unclear. The aim of this study was to compare the ultrasonographic features of PTC according to its subtype in patients undergoing thyroid surgery.MethodsIn total, 140 patients who underwent preoperative thyroid ultrasonography (US) and thyroid surgery between January 2016 and December 2016 were included. The ultrasonographic features and the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) category of each thyroid nodule were retrospectively evaluated by a single radiologist, and differences in ultrasonographic features according to the PTC subtype were assessed.ResultsAccording to histopathological analyses, there were 97 classic PTCs (62.2%), 34 follicular variants (21.8%), 5 tall cell variants (3.2%), 2 oncocytic variants (1.3%), 1 Warthin-like variant (0.6%), and 1 diffuse sclerosing variant (0.6%). Most PTCs were classified under K-TIRADS category 5. Among the ultrasonographic features, the nodule margin and the presence of calcification were significantly different among the PTC subtypes. A spiculated/microlobulated margin was the most common type of margin, regardless of the PTC subtype. In particular, all tall cell variants exhibited a spiculated/microlobulated margin. The classic PTC group exhibited the highest prevalence of intranodular calcification, with microcalcification being the most common. The prevalence of multiplicity and nodal metastasis was high in the tall cell variant group.ConclusionThe majority of PTCs in the present study belonged to K-TIRADS category 5, regardless of the subtype. Our findings suggest that ultrasonographic features are not useful for distinguishing PTC subtypes