The effect of 1,25-dihydroxyvitamin D<Subscript>3</Subscript> on TSLP,IL-33 and IL-25 expression in respiratory epithelium

Background

Airway epithelium is an active and important component of the immunological response in the pathophysiology of obstructive lung diseases. Recent studies suggest an important role for vitamin D₃ in asthma severity and treatment response.

Objective

Our study evaluated the influence of an active form of vitamin D₃ on the expression of selected mediators of allergic inflammation in the respiratory epithelium.

Material and Methods

Primary nasal and bronchial epithelial cells were exposed to1,25D₃ for 1 hour and were then stimulated or not with IL-4, TNF-α, LPS, and poly I:C. After 24 hours TSLP, IL-33, and IL-25 protein levels were measured in culture supernatants usingELISAandmRNAlevels in cells by real time PCR.

Results

1,25D₃ increased TSLP concentration in unstimulated nasal epithelial cells, but did not influence IL-33 and IL-25 expression. In IL-4-stimulated epithelial cell cultures 1,25D₃ mostly inhibited TSLP and IL-33 expression. In LPS-treated cultures 1,25D₃ decreased IL-33 expression. Simultaneously 1,25D₃ augmented IL-25 production in the same model of stimulation.

Conclusion

Our study revealed the dual nature of vitamin D₃ manifested in both pro- and anti-inflammatory properties observed in airway epithelial cells.

     

Combined effects of aspirin and vitamin D3 on two OSCC cell lines: a preliminary study

Objectives

We evaluated the potential effects of aspirin combined with vitamin D3 on cell proliferation and apoptosis in oral cancer cells.

Results

Compared to the untreated control or individual drug, the combinations of aspirin and vitamin D3 significantly decreased the rates of cell proliferation by CCK-8 assay, and caused higher rates of cell apoptosis in both CAL-27 and SCC-15 cells by Annexin V-FITC apoptosis assay and flow cytometry. Remarkably, the combined treatment with aspirin and vitamin D3 significantly suppressed the expression of Bcl-2 protein and p-Erk1/2 protein, examined by western blot analysis.

Conclusions

Our study demonstrates that aspirin and vitamin D3 have biological activity against two human OSCC cell lines and their activity is synergistic or additive when two drugs used in combination with therapeutic concentrations. The combination of aspirin and vitamin D3 may be an effective approach for inducing cell death in OSCC.

     

Metabolic response of porcine colon explants to in vitro infection by <Emphasis Type="Italic">Brachyspira hyodysenteriae</Emphasis>: a leap into disease pathophysiology

Introduction

Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available.

Objective

The aim of this study was to characterize the metabolic response of porcine colon explants to infection by B. hyodysenteriae.

Methods

Porcine colon explants exposed to B. hyodysenteriae were analyzed for histopathological, metabolic and pro-inflammatory gene expression changes.

Results

Significant epithelial necrosis, increased levels of l-citrulline and IL-1α were observed on explants infected with B. hyodysenteriae.

Conclusions

The spirochete induces necrosis in vitro likely through an inflammatory process mediated by IL-1α and NO.

     

Proinflammatory cytokine responses in patients with psoriasis

Background

Psoriasis is one of the most common, immune-mediated, chronic inflammatory skin diseases. Proinflammatory cytokines play an important pathogenetic role at a local level.

Objective

To assess whether the proinflammatory cytokines IL-1β, IL-6, IL-17, IL-22 and TNF-α are released systemically during psoriasis.

Methods

Peripheral blood mononuclear cells (PBMCs) were isolated from 30 patients with psoriasis and 30 healthy volunteers. Cytokine production was assessed in supernatants using an enzyme immunoassay after stimulation of PBMCs with microbial stimuli. In addition, flow cytometry was used to determine the subsets of monocytes involved and the intracellular TNF-α production in monocytes.

Results

IL-17 levels were significantly higher in the supernatants of PBMCs from psoriatic patients after stimulation with phytohemagglutinin. TNF-α production was also significantly higher in cells from psoriatic patients after stimulation with all stimuli, as compared with health volunteers. Similar changes were not found for the other cytokines. A statistically significant difference was observed between patients and controls for inflammatory CD14⁺/CD16⁺ monocytes (p<0.0001) and patrolling CD14-/CD16⁺ monocytes.

Conclusion

Hyper-production of TNF-α is documented in psoriasis. These results support the concept that there is a systemic, proinflammatory component in psoriasis.

     

LncRNA ZEB1-AS1 contributes to STAT3 activation by associating with IL-11 in B-lymphoblastic leukemia

Objective

To investigate the role of lncRNA ZEB1-AS1 in B-lineage acute lymphoblastic leukemia (B-ALL).

Results

ZEB1-AS1 levels were aberrantly up-regulated in B-ALL. All correlated with STAT3 activation and IL-11 production. Moreover, a high level of ZEB1-AS1 predicted poor prognosis of B-ALL patients. Mechanistically, ZEB1-AS1 could bind to IL-11 and promote IL-11 stability. Down-regulation of ZEB1-AS1 decreased IL-11 production of human bone marrow stromal cells (BMSCs), which led to suppressed proliferation and inhibited IL-11/STAT3 pathway in BALL-1 cells.

Conclusions

ZEB1-AS1 promotes the activation of IL-11/STAT3 signaling pathway by associating with IL-11 in B-ALL.

     

Clinical and cytokine profile evaluation in Northeast Brazilian psoriasis plaque-type patients

Objective and Design

Psoriasis is a common, enigmatic, and recurrent disease. The precise etiology and pathogenesis of psoriasis are still unclear. Psoriasis has been treated as an inflammatory disorder related to an underlying Th1/Th17-dominated immune response. Interleukins are involved in the development of psoriasis lesions through Th-17-associated inflammation. Th1 and Th17 cytokines are found in skin lesions and in the peripheral blood of psoriasis patients.We sought to analyze serum levels of IL-1-β, IL-8, IL-9, IL-27, IL-29, IL-35, IFN-γ, TNF and TGF-β in patients with psoriasis and healthy control volunteers.

Material

Blood samples were collected from fifty-three patients with psoriasis and thirty-five healthy controls.

Methods

Serum cytokines concentrations were determined using an enzyme-linked immunosorbent assay.

Results

Serum IL-8, IL-9, IL-27, IL-29 and TNF levels were statistically significant in psoriasis patients. Detectable serum IL-9 levels were found in 47 patients of the 53 in the psoriasis group.

Conclusions

Interleukins-8, 27, 29 and TNF levels measured in the serum of psoriasis patients were slightly elevated as compared to healthy controls in a weakly significant way. On the other hand, there were highly significant differences in IL-9 levels between the two groups.

     

Low vitamin D levels are associated with cognitive impairment in patients with Hashimoto thyroiditis

Background

Cognitive impairment is commonly observed in patients with Hashimoto thyroiditis (HT). Low levels of vitamin D have been correlated with cognitive impairment in non-HT population. We examined the association of vitamin D levels with cognitive impairment in patients with HT.

Methods

We recruited 194 patients with HT and 200 healthy volunteers. Levels of serum 25-hydroxyvitamin D (25(OH)D) were measured using a competitive protein-binding assay. Cognitive funtion was assessed using Montreal Cognitive Assessment score (MoCA). Subjects with a MoCA scores <?26 are considered as having mild cognitive impairment (MCI). Multivariate analysis was performed using logistic regression models.

Results

Fifty-five HT patients (28.4%) were diagnosed as having MCI. Patients with MCI had significantly lower 25(OH)D levels when compared with patients without MCI (33.9?±?6.2 vs. 44.3?±?9.6?nmol/L, P?<?0.001). Significant differences in 25(OH)D quartiles of HT patients were observed between the patients with MCI and the patients without MCI (P?<?0.001). In multivariate analyses, serum 25(OH)D levels (≤ 34.0 and?≥?47.1?nmol/L) were significantly associated with cognitive impairment in patients with HT (OR 6.279, 95% CI 2.673–14.834, P?<?0.001; OR 0.061, 95% CI 0.008–0.491, P?=?0.009, respectively).

Conclusion

Our results demonstrate an important association between serum vitamin D levels and cognitive impairment in patients with HT.

     

Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup’ik people

Background

Vitamin D deficiency is a well-documented public health issue with both genetic and environmental determinants. Populations living at far northern latitudes are vulnerable to vitamin D deficiency and its health sequelae, although consumption of traditional native dietary pattern rich in fish and marine mammals may buffer the effects of reduced sunlight exposure. To date, few studies have investigated the genetics of vitamin D metabolism in circumpolar populations or considered genediet interactions with fish and n-3 fatty acid intake.

Methods

We searched for genomic regions exhibiting linkage and association with circulating levels of vitamin D and parathyroid hormone (PTH) in 982 Yup’ik individuals from the Center for Alaska Native Health Research Study. We also investigated potential interactions between genetic variants and a biomarker of traditional dietary intake, the δ15N value.

Results

We identified several novel regions linked with circulating vitamin D and PTH as well as replicated a previous linkage finding on 2p16.2 for vitamin D. Bioinformatic analysis revealed multiple candidate genes for both PTH and vitamin D, including CUBN, MGAT3, and NFKBIA. Targeted association analysis identified NEBL as a candidate gene for vitamin D and FNDC3B for PTH. We observed significant associations between a variant in MXD1 and vitamin D only when an interaction with the δ15N value was included. Finally, we integrated pathway level information to illustrate the biological validity of the proposed candidate genes.

Conclusion

We provide evidence of linkage between several biologically plausible genomic regions and vitamin D metabolism in a circumpolar population. Additionally, these findings suggest that a traditional dietary pattern may modulate genetic effects on circulating vitamin D.

     

Nitrous oxide induced subacute combined degeneration with longitudinally extensive myelopathy with inverted V-sign on spinal MRI: a case report and literature review

Background

Nitrous oxide (N2O), a long-standing anesthetic, is also neurotoxic by interfering with the bioavailability of vitamin B12 if abused. A few case studies have reported the neurological and psychiatric complications of N2O.

Case presentation

Here, we reported a patient of N2O induced subacute combined degeneration (SCD) with longitudinally extensive myelopathy with inverted V-sign exhibiting progressive limb paresthesia and unsteady gait.

Conclusions

This case raises the awareness of an important mechanism of neural toxicity of N2O, and clinical physicians should be well recognized this in the field of substance-related disorders.

     

NMRProcFlow: a graphical and interactive tool dedicated to 1D spectra processing for NMR-based metabolomics

Introduction

Concerning NMR-based metabolomics, 1D spectra processing often requires an expert eye for disentangling the intertwined peaks.

Objectives

The objective of NMRProcFlow is to assist the expert in this task in the best way without requirement of programming skills.

Methods

NMRProcFlow was developed to be a graphical and interactive 1D NMR (¹H & ¹³C) spectra processing tool.

Results

NMRProcFlow (http://nmrprocflow.org), dedicated to metabolic fingerprinting and targeted metabolomics, covers all spectra processing steps including baseline correction, chemical shift calibration and alignment.

Conclusion

Biologists and NMR spectroscopists can easily interact and develop synergies by visualizing the NMR spectra along with their corresponding experimental-factor levels, thus setting a bridge between experimental design and subsequent statistical analyses.

     

A metabolomics approach to uncover effects of different exercise modalities in type 1 diabetes

Introduction

Exercise-associated metabolism in type 1 diabetes (T1D) remains under-studied due to the complex interplay between exogenous insulin, counter-regulatory hormones and insulin-sensitivity.

Objective

To identify the metabolic differences induced by two exercise modalities in T1D using ultra high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC–HRMS) based metabolomics.

Methods

Twelve T1D adults performed intermittent high-intensity (IHE) and continuous-moderate-intensity (CONT) exercise. Serum samples were analysed by UHPLC–HRMS.

Results

Metabolic profiling of IHE and CONT highlighted exercise-induced changes in purine and acylcarnitine metabolism.

Conclusion

IHE may increase beta-oxidation through higher ATP-turnover. UHPLC–HRMS based metabolomics as a data-driven approach without an a priori hypothesis may help uncover distinctive metabolic effects during exercise in T1D.Clinical trial registration number is www.clinicaltrials.gov: NCT02068638.

     

Forced expression of <Emphasis Type="Italic">CD200</Emphasis> improves the differentiation capability and immunoregulatory functions of mesenchymal stromal cells

Objective

In order to identify specific mesenchymal stromal cell (MSC) populations with enhanced therapeutic efficacy, we evaluated the functional changes associated with the stable expression of CD200, which is associated with immune regulatory function and osteogenic differentiation, in human bone marrow-derived MSCs (CD200/MSCs).

Results

We detected significantly greater osteogenesis and chondrogenesis in CD200/MSCs than in mock-transfected MSCs. In addition, the immune regulatory function of MSCs in mixed lymphocyte reactions was enhanced by CD200 gene transfection. In CD200/MSCs, the secretion of inflammatory cytokines, i.e., IL-6 and IL-8, was reduced, and levels of the anti-inflammatory factors IL-10, FOXP3, and indoleamine 2,3-dioxygenase 1 were elevated. Finally, CD200 transfection increased the stemness of MSCs, as evidenced by greater colony numbers in colony-forming unit fibroblast assays and analyses of NANOG and OCT-4 expression.

Conclusions

These results suggest that CD200/MSCs have therapeutic applications, and further in-depth research should focus on the development of a clinically applicable cell-based therapeutic strategy.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

The structure of a small GTPaseRhoA in complex with PDZRhoGEF and the inhibitor HL47

Objectives

To study the structure of a small GTPaseRhoA in complex with PDZRhoGEF and the inhibitor HL47, and to provide an easier template for R&D of RhoA inhibitor.

Results

Our initial attempts to obtain a binary complex of RhoA with the inhibitor HL47 were unsuccessful probably due to the presence of GDP. By targeting a ternary complex involving the RhoA-specific guanine nucleotide exchange factor PDZRhoGEF, we eliminated GDP and obtained a 2.3 Å structure of the RhoA-PDZRhoGEF-inhibitor HL47 ternary complex.

Conclusion

This structure provides a new template for target-based pharmaceutical design against RhoA.

     

Genetic influence on serum 25-hydroxyvitamin D concentration in Korean men: a cross-sectional study

Background

Hypovitaminosis D is prevalent worldwide. It is more prevalent in Eastern Asia region, including Korea. In addition to various environmental factors that influence serum 25-hydroxyvitamin D (25(OH)D) concentration, genetic influence also plays a significant role based on studies estimating the heritability of 25(OH)D in non-Asian populations. The objective of this study was to determine the genetic influence on serum 25(OH)D concentration in Korean men using the twin and family data.

Methods

A total of 1126 Korean male adult twins and family members from the Healthy Twin Study with serum 25(OH)D measurement were included in this cross-sectional study. Intraclass correlation coefficients (ICCs) and heritability were calculated by mixed linear regression analysis and quantitative genetic analysis after adjusting for environmental and lifestyle factors.

Results

Mean (±?standard deviation; SD) of serum 25(OH)D concentration was 15.34?±?6.18?ng/ml. The prevalence of vitamin D insufficiency was 19.8% and that of vitamin D deficiency was 77.9%. After adjusting for age, the highest ICC (0.61) was observed for monozygotic twin pairs while the lowest ICC (0.31) was found for father-son pairs. Age-adjusted heritability was estimated to be 58%. When physical activity, multivitamin intake and season of blood sampling were further considered, the ICC and heritability did not materially change. In the sensitivity analysis after excluding known multivitamin users, age-adjusted heritability was reduced to 44%.

Conclusions

In our study of Korean male twins and family members, heritability of 25(OH)D was moderately high. This supports the finding that genetic factors have significant influence on vitamin D status.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

IL-1 does not reverse the anti-proliferative effect of aspirin in breast cancer cells

Objectives

Interleukin- 1 (IL-1) is a multifunctional proinflammatory cytokine. There have been studies suggesting a role in affecting growth and invasiveness of malignant breast cells by either blocking or stimulating growth of cultured MCF-7 breast cancer cells. This effect may be mediated by induction of COX-2. Aspirin is an inhibitor of COX-2 and has been implicated, with other non-steroidal anti-inflammatory drugs (NSAIDS) in prevention and treatment of breast cancer. In this study the in vitro effects of IL-1 and aspirin on growth of MCF-7 human breast cancer cells was examined.

Methods

MCF-7 cells were treated with various concentrations of IL-1 and aspirin alone and in combination. Cell growth was assessed by cell number measurement.

Results

Aspirin significantly decreased growth rate in a dose-dependant manner, alone and as a combined treatment with IL-1 with a maximum reduction in growth rate at 300 mg/ml (P < 0.05). Treatment with IL-1 alone showed no significant effect on growth rate of MCF-7 cells (P > 0.05).

Conclusion

This study confirms that aspirin suppresses the proliferation rate of MCF-7 cells both as a single agent and in combination with IL-1. It also suggests that IL-1 alone does not stimulate or inhibit growth of MCF-7 cells.

     

Cellular and clinicopathological features of the IL-33/ST2 axis in human esophageal squamous cell carcinomas

Background

Emerging evidence has suggested that interleukin (IL)-33 and its primary functional receptor ST2 are involved in the pathogenesis of tumorigenesis.

Methods

Using immunohistochemistry (IHC) and double immunofluorescence staining, we characterized the cellular and clinicopathological features of the IL-33/ST2 axis in different compartments in human esophageal squamous cell carcinoma (ESCC) surgical specimens.

Results

IHC data revealed an increased expression of IL-33-immunoreactivity (IR) and ST2-IR located in both ESCC cells and tumor stromal cells; which were associated with advanced clinicopathological features such as TNM stages and node involvement. However, the Kaplan–Meier analysis showed that densities of neither IL-33 positive nor ST2 positive cells in both the ESCC mass and stroma were associated with the overall survival rate in patients with ESCC. Double immunofluorescence staining for cellular feature analysis demonstrated that these IL-33 positive and ST2 positive cells in ESCCs were with a high proliferation rate, and IL-33-IR was frequently co-expressed with ST2-IR in both ESCC and stromal cells.

Conclusion

Significant altered cellular features of the IL-33/ST2 axis in ESCCs were associated with advanced clinicopathological variables. The data suggest that the IL-33/ST2 axis might be involved in the progression of human ESCCs.