Editor’s Choice Article | Serum Proteome Profiling to Identify Proteins Promoting Pathogenesis of Non-atopic Asthma

Journal Name: Protein & Peptide Letters

Author(s): Samina Ejaz, Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan Faiz-ul-Hassan Nasim*, Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, Pakistan Muhammad Ashraf, Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, Pakistan Sami Ahmad. Department of Pulmonolgy, Quaid-i-Azam Medical College, Bahawal Victoria Hospital, Bahawalpur, Pakistan

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Abstract:

Background: Asthma is the inflammatory disorder of airways highly prevalent in both, children and adults all over the world. The aim of this study was to investigate the serum proteome for the identification of proteins contributing to the pathogenesis of non-atopic asthma.

Methods: Protein expression profiling of sera from non-atopic asthmatic patients (n=73) and controls (n=99) was carried out using 1D SDS PAGE. Differentially expressed protein bands were compared with controls, cut from the gel and identified by LC-Q-TOF_MSMS analysis.

Results: Various acute phase proteins (i.e., haptoglobin, transthyretin, serum amyloid A, and serum albumin), retinol binding protein 4 (RBP4), Ig gamma-1-chain C-region, hemoglobin subunit β, complement system components (C8 gamma chain and C4-A), ApoA-1 and Ig κ chain C-region containing protein fractions were predominantly down-regulated in asthmatic patients. Similarly, a higher proportion of male patients exhibited down-regulation of all other (except albumin and C4-A containing) protein fractions as compared to female patients. However, fractions consisting of another acute phase protein, inter-alpha-trypsin heavy chain 4 (ITIH4) and complement system component C3 were up-regulated in the majority of patients.

Conclusion: Our study is the first to confirm the role of thyroxine (TTR), retinol (RBP4), cholesterol (apoA-1) transporting proteins, inflammation and its mediators in the pathogenesis of asthma. Further study may help to improve diagnosis and plan better treatment strategies.

 

 

Read out more at: http://www.eurekaselect.com/165657/article

 

 

ARTICLE TO READ ON WORLD ASTHMA DAY

Maternal Vitamin D Status and Development of Asthma and Allergy in Early Childhood

Author(s): Anna Papadopoulou, Evangelia Bountouvi, Vasiliki Papaevaggelou, Kostas N. Priftis.

Abstract:

Vitamin D has an indisputable immunodulatory role in both lung and immune system development, which is initiated during fetal life and is mainly accomplished in the first years of extrauterine life. Several published studies have shown that low levels of vitamin D may increase the risk of developing asthma and allergic diseases. Moreover, vitamin D deficiency epidemic reported over the last decades coincides with an increase in the prevalence of asthma and allergies in westernized societies. Since placental transfer of 25(OH)D is the major source of vitamin D in the developing fetus, important questions concerning the impact of maternal vitamin D status on the outcome of pregnancy have arisen. The aim of this review is to present the current evidence regarding the determinants of vitamin D status in pregnancy as well as its role in the development of asthma and allergies in early childhood.

Read more here: http://www.eurekaselect.com/131440

 

PRESS RELEASE – LC-MS/MS Identification and characterization of biodegradation products of Nitroproston

This article by Dr. Natalia Vladimirovna Mesonzhnik et al. is published in Drug Metabolism Letters, Volume 12, 2018

Nitroproston (11(S),15(S)-dihydroxy-9-keto-5Z,13E-prostadienoic acid 1?,3?-dinitroglycerol ester) is a novel prostaglandin-based compound with potential application in obstructive respiratory diseases such as asthma and obstructive bronchitis. Its pharmacological activity is provided by combined multi-target action on prostanoid EP4 receptors and soluble guanylylcyclase. Nitroproston is bearing a prostaglandin E2 (PGE2) moiety modified by an additional NO-donating fragment of glycerol-1,3-dinitrate (1,3-GDN) via ester bond and can be consider as nitrated derivative of glycerol ester of PGE2 ? the natural COX-2 metabolite of endogenous cannabinoid-like molecule 2-arachidonoyl glycerol. The presence of NO-donating fragment extremely changes pharmacological properties of PGE2. Nitroproston is more than 20-fold as active as prostaglandin E2 in the relaxation of respiratory muscles. Due to this enhanced myorelaxant activity Nitroproston is well tolerated by asthmatic subjects and is the first-in-class pharmaceutical candidate for therapy of asthma attacks utilized both prostanoid and NO receptors.

Despite the fact that Nitroproston has been extensively studied using various pharmacological models, its biological stability is still unknown. Thereby, the main aim of the present study was to evaluate Nitroproston stability in vitro, as well as to identify and characterize its biodegradation products. The principal in vitro biodegradation products of Nitroproston were identified using liquid chromatography/ion trap – time-of-flight mass-spectrometry (LC-HRMS/MS). The postulated structure of metabolites was confirmed using authentic reference standards. Rat, rabbit and human plasma and human whole blood samples were used for comparative in vitro degradation study. Nitroproston and its biodegradation products in biological samples were measured by target liquid chromatography/triple-stage quadrupole mass spectrometry (LC-MS/MS).

LC-HRMS/MS of spiked rat plasma samples clearly indicated the presence of two main metabolites of Nitroproston – 1,3-GDN and PGE2, the later can undergo dehydration to cyclopentenone prostaglandins. The applied LC-HRMS/MS screening method did not reveal the presence of biodegradation products of Nitroproston with one nitro-group or PGE2 glycerol ester. We assume that nitrate esters are more resistant to enzymatic hydrolysis in rat plasma than carboxyl ester moieties.

Target LC-MS/MS quantitative analysis was used to quantify the amount of Nitroproston and its major biodegradation products in rodent’s plasma. The degradation was higher in rat plasma where only 5 % of parent Nitroproston was identified at the first moment of incubation. Similar pattern was observed for rabbit plasma where half-life (T1/2) of Nitroproston was about 2.0 minutes. Additionally, whole human blood and plasma samples were taken to perform stability and blood cell distribution study. Nitroproston biodegradation rate for human plasma was the slowest (T1/2 = 2.1 h) among tested species, but occurred more rapidly in whole blood (T1/2 = 14.8 min). Nitroproston was distributed between human RBCs and plasma with partition ratio of 0.82. These data suggest that metabolism of drug candidate in human whole blood was mainly associated with an enzymes located in RBC fraction. The observed interspecies variability highlights the need of suitable animal model selection for Nitroproston follow-up PK/PD studies. Our findings do not exclude that Nitroproston may be relatively stable in human after inhalation and may exert its therapeutic actions either as a whole drug molecule or as a prostaglandin E2 and nitric oxide prodrugs thanks to its active metabolites.

Nitroproston is being developed as a drug candidate for relief of bronchial asthma. The key principle of the action of Nitroproston is not only the effect on two targets having similar pharmacological activity with respect to bronchial smooth muscle, but also the synchronization of the pharmacological activity when the prostaglandin E2 is the driver of the donor part releasing the NO in the activity sites. Due to this, a powerful synergy of pharmacological activity is achieved and the dose of PGE2 drops sharply, which brings us back to the possibility of starting new and more successful attempts to use the of NO donating PGE2 derivatives for relief the bronchial asthma.

For more information about the research, please visit: http://www.eurekaselect.com/160373/article

OPEN ACCESS ARTICLE – An Update on Anti-IgE Therapy in Pediatric Respiratory Diseases – Current Respiratory Medicine Reviews

Journal: Current Respiratory Medicine Reviews

Author(s): 

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Abstract:

Anti-IgE treatment represents a major breakthrough in the therapeutic management of severe allergic asthma. Omalizumab is the unique biologic treatment registered for asthma therapy in children. The clinical efficacy and safety of omalizumab treatment in the pediatric population has been extensively documented in specific trials and consistently expanded from real-life studies. In addition, new experimental evidence suggests that omalizumab may also interfere with the cellular and molecular mechanisms underlying airway remodeling. Novel investigational anti-IgE monoclonal antibodies with improved pharmacodynamic properties are in the pipeline, potentially offering alternative mechanisms of modulating IgE pathway.

The aim of this review is to update current knowledge on anti-IgE therapy in pediatric respiratory diseases.

Read more here: http://www.eurekaselect.com/153354

 

Winter Brings Some Common Ailments

Winter is fast approaching again and we are all set to welcome it. Our warm clothes are out, blankets lay ready on beds, heaters are on and now we are looking to gather the most essential medicines we need this season. Here are some common ailments that we need to brace ourselves against.

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Cold

It gets extremely easy to catch cold in winter. These can be simple colds or the deadly pneumonia that we are vulnerable to, as the viruses and bacteria spread in the cold weather. We can prevent ourselves and family by keeping the house and surroundings clean. Also, we need to regularly wash our hands before eating and doing our daily chores.

Joint Pains

If you suffer from arthritis or other bones and joint problems, you need to be extra careful. The pain in joints and bones increases with lower temperatures. The real cause for this is not clear but this phenomenon is very common and disturbing.

Sore Throat

Infections that cause sore throat become highly active too. We have to keep avoiding chilled drinks and water and keep warm throughout the day. If you fall ill try gargling with salt dissolved in warm water. This will soothe the throat.

Asthma

Asthma patients are very likely to have their problem aggravated, especially if dry, cold winds are blowing in winter. We can generally find our oxygen levels reduce and moisture lost in windy season. This can be dangerous and should not be neglected. We need to keep the medicines and asthma pumps ready at all times to get instant help when needed.

Stomach Aches & Nausea

Norovirus is what creates stomach issues in cold season. Nausea, diarrhea, and constant stomach aches are telltale signs of norovirus. It takes its time to cure and we need to keep patience and general measures to bring our bellies back to normal.

There are many more issues that may be more severe and we need to adopt a healthy lifestyle to keep them all at bay.

 

 

Most Accessed Article – “Innovative Targets For Asthma And COPD: Exploring The Existing And Screening The New!!”

Journal: Infectious Disorders – Drug Targets

Author(s): Preeti Vyas, Divya Vohora

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Abstract:

The inadequate benefits of the existing therapies and the new insights into the pathophysiology of inflammatory airway diseases like chronic obstructive pulmonary disease (COPD) and asthma have led to the breakthrough of newer targets and innovative compounds as the treatment alternatives. The enhanced interpretation of immune cell signalling and signal transduction pathways at the molecular level involved in this process allows the selection of new therapeutic targets and designing of new molecules to combat such multifactorial diseases. Pertaining to the marked variability in type of inflammation observed in their disease phenotypes, the blockade of a particular receptor or mediator yielding strong restorative effect in one patient may not be significant to other. Therefore, their management requires the prompt and phenotype specific optimized drug therapies and development of new and improved molecular compounds targeting the immune cell signalling. This whole process including the approval of such compounds as the standard drug therapies is time taking, expensive and complicated task. It ranges from the selection of novel anti-inflammatory drug target to the final approval of biologically active restorative molecules. Grounded on this, the current review gives a comprehensive idea of the basic immunological network involved in these inflammatory airway diseases at the cellular level along with the discussion of their potential therapeutic targets. It also follows brief over viewing of the drug development process generally employed for the exploration of such innovative targets leading to the discovery of novel anti-inflammatory molecules for these inflammatory airway diseases.

To access the article, please visit: http://www.eurekaselect.com/144228

Article by Disease – “Role of Galectins in Allergic Disorders”

Article by Disease on “Allergy”

Abstract:

Background: Allergen avoidance, pharmacotherapy; with antihistamines, anti-leukotrienes, corticosteroids and bronchodilatorsas well as monoclonal antibodies; and allergen specific immunotherapy stand as confirmed approaches for the management of allergic disorders as asthma, allergic rhinitis/rhinoconjunctivitis, atopic dermatitis, food allergies and anaphylaxis. Galectins are members of animal lectin protein family, with binding specificity for β-galactoside sugars. These highly conserved proteins are known to be expressed in various effector cells of the immune system, exert immuno-regulatory activities, and enroll in tissue inflammation and regulation of immune homeostasis.

Objective: This review aims to explain the galectin family and influence of galectins in the immune mechanisms of allergic disorders.

Results: Galectins have multiple roles in innate and adaptive immunity. Intense research in the field of immunology related with galectins have given rise to several patent applications. Those, increasing in vivo efficacy of galectins for therapeutic applications, utilizing galectins for immune stimulation and prolongation of immune responses, utilization of them as disease markers are pioneers. As immune cells can be targeted by galectins, cells containing these molecules can be used for immune intervention. Regulation of cytokine productions by immune cells as IL-1β and IL-10 as well as dendritic cell functions by galectins may be efficient in limitation of some immune-mediated disorders.

Conclusion: Taken all together, better learning of galectin biology together with detailed revealing of galectin-immune system interactions have great potential for immune interventions targeting allergy-related disorders.

Read more: http://benthamscience.com/journals/recent-patents-on-inflammation-and-allergy-drug-discovery/volume/10/issue/1/page/2/

Article by Disease – “Role of Galectins in Allergic Disorders”

Article by Disease on “Allergy”

Abstract:

Background: Allergen avoidance, pharmacotherapy; with antihistamines, anti-leukotrienes, corticosteroids and bronchodilators as well as monoclonal antibodies; and allergen specific immunotherapy stand as confirmed approaches for the management of allergic disorders as asthma, allergic rhinitis/rhinoconjunctivitis, atopic dermatitis, food allergies and anaphylaxis. Galectins are members of animal lectin protein family, with binding specificity for β-galactoside sugars. These highly conserved proteins are known to be expressed in various effector cells of the immune system, exert immuno-regulatory activities, and enroll in tissue inflammation and regulation of immune homeostasis.

Objective: This review aims to explain the galectin family and influence of galectins in the immune mechanisms of allergic disorders.

Results: Galectins have multiple roles in innate and adaptive immunity. Intense research in the field of immunology related with galectins have given rise to several patent applications. Those, increasing in vivo efficacy of galectins for therapeutic applications, utilizing galectins for immune stimulation and prolongation of immune responses, utilization of them as disease markers are pioneers. As immune cells can be targeted by galectins, cells containing these molecules can be used for immune intervention. Regulation of cytokine productions by immune cells as IL-1β and IL-10 as well as dendritic cell functions by galectins may be efficient in limitation of some immune-mediated disorders.

Conclusion: Taken all together, better learning of galectin biology together with detailed revealing of galectin-immune system interactions have great potential for immune interventions targeting allergy-related disorders.

http://benthamscience.com/journals/recent-patents-on-inflammation-and-allergy-drug-discovery/volume/10/issue/1/page/2/

SMI EVENT-13th Asthma & COPD!

SMi’s ‘Asthma & COPD’ returns to London in March 2017 to reflect on the ongoing issues and latest developments to these two diseases.

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DESCRIPTION:  The SMi Group is proud to announce the return of the 13th annual Asthma & COPD conference taking place in London on the 29-30 March 2017. Aimed at senior scientists and respiratory and inhalation specialists, Asthma & COPD 2017 will reflect on the ongoing issues and latest developments of these two diseases. With a carefully selected panel of industry experts, the 2017 event will address the latest challenges and changes in the fields of asthma and COPD. The agenda will explore ongoing issues, cutting edge developments and novel approaches to treatment surrounding key areas such as biomarkers and targeted treatment, device development and drug delivery. Furthermore the event will deepen understanding of the problems relating to these respiratory diseases, and discuss the hot topic of electronic health monitoring. Hear from MHRA, Mylan, AstraZeneca, Teva UK, GlaxoSmithKline, Boehringer Ingelheim, Glenmark Pharmaceuticals, Janssen, AstraZeneca, Novartis and many more… Early birds available.

For details please visit:  www.asthma-copd.co.uk/bentham

Related Journal: Current Respiratory Medicine Reviews

Related eBook: Frontiers in Clinical Drug Research-Anti Infectives

Asthma Patients Need Our Help!

Today is World Asthma Day 2016; a day when we show our concern and support for asthma sufferers. Asthma is such a common problem that it needs no introduction. Many a people around the world suffer with this respiratory condition which causes them suffocation and severe problem in breathing. So far no one reason has been identified as the cause of asthma. It can be due to the environment being non-supportive or it can be due to a state called hypersensitivity of the sufferer him or herself. Certain people allergic to something may also have to bear the discomfort in breathing.

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Research team from Department of Biotechnology, Maharishi Markandeshwar University, India has raised the point that asthma is also dependent on the presence, forms and behavior of certain genes. The people carrying the genes prone to asthma can render the people to be hypersensitive to allergies. Deciphering the genes and finding the right drug formulation that can cure or prevent the condition can be vital in eliminating asthma completely or partially at least from the planet.

Their research paper, Recent Advances in Asthma Genetics and Antiasthma Therapy, which was published in Current Respiratory Medicine Reviews explains the research.

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