Association between HMGB1 and asthma: a literature review

Background

Recently, some studies demonstrated that HMGB1, as proinflammatory mediator belonging to the alarmin family, has a key role in different acute and chronic immune disorders. Asthma is a complex disease characterised by recurrent and reversible airflow obstruction associated to airway hyper-responsiveness and airway inflammation.

Objective

This literature review aims to analyse advances on HMGB1 role, employment and potential diagnostic application in asthma.

Methods

We reviewed experimental studies that investigated the pathogenetic role of HMGB in bronchial airway hyper-responsiveness, inflammation and the correlation between HMGB1 level and asthma.

Results

A total of 19 studies assessing the association between HMGB1 and asthma were identified.

Conclusions

What emerged from this literature review was the confirmation of HMGB-1 involvement in diseases characterised by chronic inflammation, especially in pulmonary pathologies. Findings reported suggest a potential role of the alarmin in being a stadiation method and a marker of therapeutic efficacy; finally, inhibiting HMGB1 in humans in order to contrast inflammation should be the aim for future further studies.

     

Synthesis and physicochemical characterization of the one-carbon carrier 10-formyltetrahydrofolate; a reference standard for metabolomics

Introduction

Metabolomics analysis depends on the identification and validation of specific metabolites. This task is significantly hampered by the absence of well-characterized reference standards. The one-carbon carrier 10-formyltetrahydrofolate acts as a donor of formyl groups in anabolism, where it is a substrate in formyltransferase reactions in purine biosynthesis. It has been reported as an unstable substance and is currently unavailable as a reference standard for metabolomics analysis.

Objectives

The current study was undertaken to provide the metabolomics community thoroughly characterized 10-formyltetrahydrofolate along with analytical methodology and guidelines for its storage and handling.

Methods

Anaerobic base treatment of 5,10-methenyltetrahydrofolate chloride in the presence of antioxidant was utilized to prepare 10-formyltetrahydrofolate.

Results

Pure 10-formyltetrahydrofolate has been prepared and physicochemically characterized. Conditions toward maintaining the stability of a solution of the dipotassium salt of 10-formyltetrahydrofolate have been determined.

Conclusion

This study describes the facile preparation of pure (>90%) 10-formyltetrahydrofolate, its qualitative physicochemical characterization, as well as conditions to enable its use as a reference standard in physiologic samples.

     

rDolphin: a GUI R package for proficient automatic profiling of 1D <Superscript>1</Superscript>H-NMR spectra of study datasets

Introduction

Adoption of automatic profiling tools for ¹H-NMR-based metabolomic studies still lags behind other approaches in the absence of the flexibility and interactivity necessary to adapt to the properties of study data sets of complex matrices.

Objectives

To provide an open source tool that fully integrates these needs and enables the reproducibility of the profiling process.

Methods

rDolphin incorporates novel techniques to optimize exploratory analysis, metabolite identification, and validation of profiling output quality.

Results

The information and quality achieved in two public datasets of complex matrices are maximized.

Conclusion

rDolphin is an open-source R package (http://github.com/danielcanueto/rDolphin) able to provide the best balance between accuracy, reproducibility and ease of use.

     

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.

     

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.

     

Stress amplifies sex differences in primate prefrontal profiles of gene expression

Background

Stress is a recognized risk factor for mood and anxiety disorders that occur more often in women than men. Prefrontal brain regions mediate stress coping, cognitive control, and emotion. Here, we investigate sex differences and stress effects on prefrontal cortical profiles of gene expression in squirrel monkey adults.

Methods

Dorsolateral, ventrolateral, and ventromedial prefrontal cortical regions from 18 females and 12 males were collected after stress or no-stress treatment conditions. Gene expression profiles were acquired using HumanHT-12v4.0 Expression BeadChip arrays adapted for squirrel monkeys.

Results

Extensive variation between prefrontal cortical regions was discerned in the expression of numerous autosomal and sex chromosome genes. Robust sex differences were also identified across prefrontal cortical regions in the expression of mostly autosomal genes. Genes with increased expression in females compared to males were overrepresented in mitogen-activated protein kinase and neurotrophin signaling pathways. Many fewer genes with increased expression in males compared to females were discerned, and no molecular pathways were identified. Effect sizes for sex differences were greater in stress compared to no-stress conditions for ventromedial and ventrolateral prefrontal cortical regions but not dorsolateral prefrontal cortex.

Conclusions

Stress amplifies sex differences in gene expression profiles for prefrontal cortical regions involved in stress coping and emotion regulation. Results suggest molecular targets for new treatments of stress disorders in human mental health.

     

Extensive myelitis associated with anti-NMDA receptor antibodies

Background

Encephalitis with anti-N-methyl-D-aspartate receptor antibodies (anti-NMDAR-Ab) is a rapid-onset encephalitis including psychosis, seizures, various movement disorders and autonomic system disturbances.

Case presentation

We report a very unusual case of extensive myelitis associated with anti-NMDAR-Ab. MRI also revealed a hyperintense T2 lesion, non-suggestive of MS, which progressively extended, associated with periventricular gadolinium enhancement visualized on brain MRI. Ophthalmological evaluation showed subclinical right optic neuritis. The absence of anti-AQP4 antibody argued against neuromyelitis optica spectrum disorder. A slight psychomotor slowing prompted us to search for various causes of autoimmune encephalitis. Anti-NMDAR-Ab was found in cerebrospinal fluid.

Conclusion

In patients with extensive myelitis who are seronegative for anti-AQP4 antibodies, and after other classical causes have been excluded, the hypothesis of atypical anti-NMDAR-Ab encephalitis should also be considered.

     

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.

     

Stimulation of mouse vibrissal follicle growth by recombinant human fibroblast growth factor 20

Objectives

To explore potential effects of recombinant human fibroblast growth factor 20 (rhFGF20) in the growth of cultured mouse vibrissal follicles.

Results

The growth of cultured mouse vibrissal follicles was significantly induced by rhFGF20 in a dose dependent pattern in the in vitro vibrissal follicle organ culture model. However, too high concentration of rhFGF20 could inhibit the growth of vibrissal follicles. We further demonstrated that rhFGF20 stimulated the proliferation of hair matrix cells and activated Wnt/β-catenin signaling pathway.

Conclusions

The rhFGF20 might be a potential therapeutic agent to treat hair loss disorders.

     

The journey of gut microbiome – An introduction and its influence on metabolic disorders

Background

Metabolic disorders such as Obesity, Diabetes Type 2 (T2DM) and Inflammatory Bowel Diseases (IBD) are the most prevalent globally. Recently, there has been a surge in the evidence indicating the correlation between the intestinal microbiota and development of these metabolic conditions apart from predisposing genetic and epigenetic factors. Gut microbiome is pivotal in controlling the host metabolism and physiology. But imbalances in the microbiota patterns lead to these disorders via several pathways. Animal and human studies so far have concentrated mostly on metagenomics for the whole microbiome characterization to understand how microbiome supports health in general. However, the accurate mechanisms connecting the metabolic disorders and alterations in gut microbial composition in host and the metabolites employed by the microorganisms in regulating the metabolic disorders is still vague.

Objective

The review delineates the latest findings about the role of gut microbiome to the pathophysiology of Obesity, IBD and Diabetes Mellitus. Here, we provide a brief introduction to the gut microbiome followed by the current therapeutic interventions in restoration of the disrupted intestinal microbiota.

Methods

A methodical PubMed search was performed using keywords like “gut microbiome,” “obesity,” “diabetes,” “IBD,” and “metabolic syndromes.” All significant and latest publications up to January 2018 were accounted for the review.

Results

Out of the 93 articles cited, 63 articles focused on the gut microbiota association to these disorders. The rest 18 literature outlines the therapeutic approaches in maintaining the gut homeostasis using probiotics, prebiotics and faecal microbial transplant (FMT).

Conclusion

Metabolic disorders have intricate etiology and thus a lucid understanding of the complex host-microbiome inter-relationships will open avenues to novel therapeutics for the diagnosis, prevention and treatment of the metabolic diseases.

     

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.

     

Urinary metabolic profiling of asymptomatic acute intermittent porphyria using a rule-mining-based algorithm

Introduction

Metabolomic profiling combines Nuclear Magnetic Resonance spectroscopy with supervised statistical analysis that might allow to better understanding the mechanisms of a disease.

Objectives

In this study, the urinary metabolic profiling of individuals with porphyrias was performed to predict different types of disease, and to propose new pathophysiological hypotheses.

Methods

Urine ¹H-NMR spectra of 73 patients with asymptomatic acute intermittent porphyria (aAIP) and familial or sporadic porphyria cutanea tarda (f/sPCT) were compared using a supervised rule-mining algorithm. NMR spectrum buckets bins, corresponding to rules, were extracted and a logistic regression was trained.

Results

Our rule-mining algorithm generated results were consistent with those obtained using partial least square discriminant analysis (PLS-DA) and the predictive performance of the model was significant. Buckets that were identified by the algorithm corresponded to metabolites involved in glycolysis and energy-conversion pathways, notably acetate, citrate, and pyruvate, which were found in higher concentrations in the urines of aAIP compared with PCT patients. Metabolic profiling did not discriminate sPCT from fPCT patients.

Conclusion

These results suggest that metabolic reprogramming occurs in aAIP individuals, even in the absence of overt symptoms, and supports the relationship that occur between heme synthesis and mitochondrial energetic metabolism.

     

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.

     

Identification of a urine metabolite constellation characteristic for kidney allograft rejection

Introduction

Allograft rejection is still an important complication after kidney transplantation. Currently, monitoring of these patients mostly relies on the measurement of serum creatinine and clinical evaluation. The gold standard for diagnosing allograft rejection, i.e. performing a renal biopsy is invasive and expensive. So far no adequate biomarkers are available for routine use.

Objectives

We aimed to develop a urine metabolite constellation that is characteristic for acute renal allograft rejection.

Methods

NMR-Spectroscopy was applied to a training cohort of transplant recipients with and without acute rejection.

Results

We obtained a metabolite constellation of four metabolites that shows promising performance to detect renal allograft rejection in the cohorts used (AUC of 0.72 and 0.74, respectively).

Conclusion

A metabolite constellation was defined with the potential for further development of an in-vitro diagnostic test that can support physicians in their clinical assessment of a kidney transplant patient.

     

Determinants of exclusive breastfeeding among mothers in Ghana: a cross-sectional study

Background

Mothers are encouraged to practice exclusive breastfeeding for the first six months of a child’s life. The general objective of the study was to assess the predictors of exclusive breastfeeding among mothers in Ghana.

Methods

This was a cross-sectional study using data from the 2008 Ghana Demographic and Health Survey (GDHS). The study sample (n = 316) was based on infants (0–5 months old) during the survey period; extracted from the individual (women) data set. Binary logistic regression was used to examine the association between selected independent variables.

Results

In general, the rate of exclusive breastfeeding was 64 percent. Marital status, region and place of delivery were found to be associated with the practice of exclusive breastfeeding. The logistic regression model illustrated mothers from the Volta Region, those who delivered in a government health facility, and mothers who perceived their infants to be average in size were more likely to practice exclusive breastfeeding.

Conclusion

Appropriate health education programmes by the Ministry of Health targeting mothers who are less likely to practice exclusive breastfeeding are recommended.

     

NMR-based metabolic characterization of chicken tissues and biofluids: a model for avian research

Introduction

Poultry is one of the most consumed meat in the world and its related industry is always looking for ways to improve animal welfare and productivity. It is therefore essential to understand the metabolic response of the chicken to new feed formulas, various supplements, infections and treatments.

Objectives

As a basis for future research investigating the impact of diet and infections on chicken’s metabolism, we established a high-resolution proton nuclear magnetic resonance (NMR)-based metabolic atlas of the healthy chicken (Gallus gallus).

Methods

Metabolic extractions were performed prior to ¹H-NMR and 2D NMR spectra acquisition on twelve biological matrices: liver, kidney, spleen, plasma, egg yolk and white, colon, caecum, faecal water, ileum, pectoral muscle and brain of 6 chickens. Metabolic profiles were then exhaustively characterized.

Results

Nearly 80 metabolites were identified. A cross-comparison of these matrices was performed to determine metabolic variations between and within each section and highlighted that only eight core metabolites were systematically found in every matrice.

Conclusion

This work constitutes a database for future NMR-based metabolomic investigations in relation to avian production and health.

     

Effect of experimental gingivitis induction and erythritol on the salivary metabolome and functional biochemistry of systemically healthy young adults

Introduction

Understanding the changes occurring in the oral ecosystem during development of gingivitis could help improve prevention and treatment strategies for oral health. Erythritol is a non-caloric polyol proposed to have beneficial effects on oral health.

Objectives

To examine the effect of experimental gingivitis and the effect of erythritol on the salivary metabolome and salivary functional biochemistry.

Methods

In a two-week experimental gingivitis challenge intervention study, non-targeted, mass spectrometry-based metabolomic profiling was performed on saliva samples from 61 healthy adults, collected at five time-points. The effect of erythritol was studied in a randomized, controlled trial setting. Fourteen salivary biochemistry variables were measured with antibody- or enzymatic activity-based assays.

Results

Bacterial amino acid catabolites (cadaverine, N-acetylcadaverine, and α-hydroxyisovalerate) and end-products of bacterial alkali-producing pathways (N-α-acetylornithine and γ-aminobutyrate) increased significantly during the experimental gingivitis. Significant changes were found in a set of 13 salivary metabolite ratios composed of host cell membrane lipids involved in cell signaling, host responses to bacteria, and defense against free radicals. An increase in mevalonate was also observed. There were no significant effects of erythritol. No significant changes were found in functional salivary biochemistry.

Conclusions

The findings underline a dynamic interaction between the host and the oral microbial biofilm during an experimental induction of gingivitis.

     

Pseudo current density maps of electrophysiological heart,nerve or brain function and their physical basis

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.

     

The effect of family policies and public health initiatives on breastfeeding initiation among 18 high-income countries: a qualitative comparative analysis research design

Background

The objective of this study is to examine the effects of macro-level factors – welfare state policies and public health initiatives – on breastfeeding initiation among eighteen high-income countries.

Methods

This study utilizes fuzzy-set Qualitative Comparative Analysis methods to examine the combinations of conditions leading to both high and low national breastfeeding initiation rates among eighteen high-income countries.

Results

The most common pathway leading to high breastfeeding initiation is the combination of conditions including a high percentage of women in parliament, a low national cesarean section rate, and either low family spending, high rates of maternity leave, or high rates of women working part-time. The most common pathway leading to low breastfeeding initiation includes the necessary condition of low national adherence to the Baby-Friendly Hospital Initiative.

Conclusion

This research suggests that there is a connection between broad level welfare state polices, public health initiatives, and breastfeeding initiation. Compliance with the WHO/UNICEF initiatives depends on welfare regime policies and overall support for women in both productive and reproductive labor.