scholarly journals In Silico Design of Multi-Epitope ESAT-6:Ag85b:Fcγ2a Fusion Protein as a Novel Candidate for Tuberculosis Vaccine

Author(s):  
Masoud Keikha ◽  
Mohsen Karbalaei ◽  
Kiarash Ghazvini

: Mycobacterium tuberculosis (MTB), which is the causative agent of tuberculosis (TB), is among the most important infectious bacteria with high morbidity and mortality rates worldwide. Bacilli Calmette-Guerin (BCG) vaccine has been discovered for about a century, and it is considered as a major vaccine for humans. However, some factors, such as its attenuated nature and its inefficacy against the latent form of the disease, have led to the use of alternative vaccines. Multi-epitope subunit vaccines are new-generation vaccines that are being developed in clinical trial phases. For the production of a subunit vaccine, the selection of immunodominant antigens and targeted delivery systems to antigen presenting cells (APCs) are considered as basic parameters. In the present study, we designed the novel multi-epitope ESAT-6:Ag85B:Fcγ2a, which was evaluated completely by various online tools as an optimum vaccine against TB. The early secreted antigenic target of 6 kDa (ESAT-6) and antigen 85B (Ag85B) are two immunodominant antigens, and Fcγ2a is a targeted delivery system. This vaccine candidate can be used for future preclinical studies.

2018 ◽  
Author(s):  
Christopher J. Smedley ◽  
Bing Gao ◽  
Suhua Li ◽  
Qinheng Zheng ◽  
Andrew Molino ◽  
...  

Sulfur-Fluoride Exchange (SuFEx) is the new generation click chemistry transformation exploiting the unique properties of S-F bonds and their ability to undergo near-perfect reactions with nucleophiles. We report here the first SuFEx based protocol for the efficient synthesis of pharmaceutically important triflones and bis(trifluoromethyl)sulfur oxyimines from the corresponding sulfonyl fluorides and iminosulfur oxydifluorides, respectively. The new protocol involves the rapid exchange of the S-F bond with trifluoromethyltrimethylsilane (TMSCF<sub>3</sub>) upon activation with potassium bifluoride in anhydrous DMSO. The reaction tolerates a wide selection of substrates and proceeds under mild conditions without need for chromatographic purification. A tentative catalytic mechanism is proposed supported by DFT calculations, involving formation of the free trifluoromethyl anion followed by nucleophilic displacement of the S-F through a five-coordinate intermediate. The preparation of a benzothiazole derived bis(trifluoromethyl)sulfur oxyimine with cytotoxic selectivity for MCF7 breast cancer cells demonstrates the utility of this methodology for the late-stage functionalization of bioactive molecules.<br>


2021 ◽  
Vol 22 (13) ◽  
pp. 6850
Author(s):  
Seyyed Mojtaba Mousavi ◽  
Seyyed Alireza Hashemi ◽  
Sonia Bahrani ◽  
Khadije Yousefi ◽  
Gity Behbudi ◽  
...  

In this review, the unique properties of intrinsically conducting polymer (ICP) in biomedical engineering fields are summarized. Polythiophene and its valuable derivatives are known as potent materials that can broadly be applied in biosensors, DNA, and gene delivery applications. Moreover, this material plays a basic role in curing and promoting anti-HIV drugs. Some of the thiophene’s derivatives were chosen for different experiments and investigations to study their behavior and effects while binding with different materials and establishing new compounds. Many methods were considered for electrode coating and the conversion of thiophene to different monomers to improve their functions and to use them for a new generation of novel medical usages. It is believed that polythiophenes and their derivatives can be used in the future as a substitute for many old-fashioned ways of creating chemical biosensors polymeric materials and also drugs with lower side effects yet having a more effective response. It can be noted that syncing biochemistry with biomedical engineering will lead to a new generation of science, especially one that involves high-efficiency polymers. Therefore, since polythiophene can be customized with many derivatives, some of the novel combinations are covered in this review.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 140
Author(s):  
Abdellatif Bouazzaoui ◽  
Ahmed A. H. Abdellatif ◽  
Faisal A. Al-Allaf ◽  
Neda M. Bogari ◽  
Saied Al-Dehlawi ◽  
...  

The current COVID-19 pandemic, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has raised significant economic, social, and psychological concerns. The rapid spread of the virus, coupled with the absence of vaccines and antiviral treatments for SARS-CoV-2, has galvanized a major global endeavor to develop effective vaccines. Within a matter of just a few months of the initial outbreak, research teams worldwide, adopting a range of different strategies, embarked on a quest to develop effective vaccine that could be effectively used to suppress this virulent pathogen. In this review, we describe conventional approaches to vaccine development, including strategies employing proteins, peptides, and attenuated or inactivated pathogens in combination with adjuvants (including genetic adjuvants). We also present details of the novel strategies that were adopted by different research groups to successfully transfer recombinantly expressed antigens while using viral vectors (adenoviral and retroviral) and non-viral delivery systems, and how recently developed methods have been applied in order to produce vaccines that are based on mRNA, self-amplifying RNA (saRNA), and trans-amplifying RNA (taRNA). Moreover, we discuss the methods that are being used to enhance mRNA stability and protein production, the advantages and disadvantages of different methods, and the challenges that are encountered during the development of effective vaccines.


Author(s):  
Yorick Bernardus Cornelis van de Grift ◽  
Nika Heijmans ◽  
Renée van Amerongen

AbstractAn increasing number of ‘-omics’ datasets, generated by labs all across the world, are becoming available. They contain a wealth of data that are largely unexplored. Not every scientist, however, will have access to the required resources and expertise to analyze such data from scratch. Fortunately, a growing number of investigators is dedicating their time and effort to the development of user friendly, online applications that allow researchers to use and investigate these datasets. Here, we will illustrate the usefulness of such an approach. Using regulation of Wnt7b expression as an example, we will highlight a selection of accessible tools and resources that are available to researchers in the area of mammary gland biology. We show how they can be used for in silico analyses of gene regulatory mechanisms, resulting in new hypotheses and providing leads for experimental follow up. We also call out to the mammary gland community to join forces in a coordinated effort to generate and share additional tissue-specific ‘-omics’ datasets and thereby expand the in silico toolbox.


2018 ◽  
Vol 76 (5) ◽  
pp. 515-537 ◽  
Author(s):  
Neeraj Bhandari ◽  
Dennis P. Scanlon ◽  
Yunfeng Shi ◽  
Rachel A. Smith

Despite growing investment in producing and releasing comparative provider quality information (CQI), consumer use of CQI has remained poor. We offer a framework to interpret and synthesize the existing literature’s diverse approaches to explaining the CQI’s low appeal for consumers. Our framework cautions CQI stakeholders against forming unrealistic expectations of pervasive consumer use and suggests that they focus their efforts more narrowly on consumers who may find CQI more salient for choosing providers. We review the consumer impact of stakeholder efforts to apply the burgeoning knowledge of consumers’ cognitive limitations to the design and dissemination of the new generation of report cards; we conclude that while it is too limited to draw firm conclusions, early evidence suggests consumers are responding to the novel design and dissemination strategies. We find that consumers continue to have difficulty accessing reliable report cards, while the media remains underused in the dissemination of report cards.


Vaccines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 75 ◽  
Author(s):  
Angita Shrestha ◽  
Jean-Remy Sadeyen ◽  
Munir Iqbal

Avian viral diseases including avian influenza, Marek’s disease and Newcastle disease are detrimental to economies around the world that depend on the poultry trade. A significant zoonotic threat is also posed by avian influenza viruses. Vaccination is an important and widely used method for controlling these poultry diseases. However, the current vaccines do not provide full protection or sterile immunity. Hence, there is a need to develop improved vaccines. The major aim of developing improved vaccines is to induce strong and specific humoral and cellular immunity in vaccinated animals. One strategy used to enhance the immunogenicity of vaccines is the selective delivery of protective antigens to antigen-presenting cells (APCs) including dendritic cells, macrophages and B cells. APCs have a central role in the initiation and maintenance of immune responses through their ability to capture, process and present antigens to T and B cells. Vaccine technology that selectively targets APCs has been achieved by coupling antigens to monoclonal antibodies or ligands that are targeted by APCs. The aim of this review is to discuss existing strategies of selective delivery of antigens to APCs for effective vaccine development in poultry.


Author(s):  
Cristina Garrigós

Forgetting and remembering are as inevitably linked as lifeand death. Sometimes, forgetting is motivated by a biological disorder, brain damage, or it is the product of an unconscious desire derived from a traumatic event (psychological repression). But in some cases, we can motivate forgetting consciously (thought suppression). It is through the conscious repression of memories that we can find self-preservation and move forward, although this means that we create a fable of our lives, as Nietzsche says in his essay “On the Uses and Disadvantages of History for Life” (1997). In Jonathan Franzen’s novel, Purity (2015), forgetting is an active and conscious process by which the characters choose to forget certain episodes of their lives to be able to construct new identities. The erased memories include murder, economical privileges derived from illegal or unethical commercial processes, or dark sexual episodes. The obsession with forgetting the past links the lives of the main characters, and structures the narrative of the novel. The motivated erasure of memories becomes, thus, a way that the characters have to survive and face the present according to a (fake) narrative that they have constructed. But is motivated forgetting possible? Can one completely suppress facts in an active way? This paper analyses the role of forgetting in Franzen’s novel in relation to the need in our contemporary society to deny, hide, or erase uncomfortable data from our historical or personal archives; the need to make disappear stories which we do not want to accept, recognize, and much less make known to the public. This is related to how we manage information in the age of technology, the “selection” of what is to be the official story, and how we rewrite our own history


2021 ◽  
Vol 85 ◽  
pp. 227-244
Author(s):  
María Sandra Peña-Cervel ◽  
Andreea Rosca

This paper provides evidence of the fruitfulness of combining analytical categories from Cognitive Linguistics and Critical Discourse Analysis for the analysis of complex literary characterizations. It does so through a detailed study of the “tributes”, i.e. the randomly selected children who have to fight to death in a nationally televised show, in The Hunger Games. The study proves the effectiveness of such categories to provide an analytically accurate picture of the dystopian world depicted in the novel, which is revealed to include a paradoxical element of hope. The type of dehumanization that characterizes the dystopian society of Panem is portrayed through an internally consistent set of ontological metaphors which project negative aspects of lower forms of existence onto people. This selection of metaphors promotes a biased perspective on the poor inhabitants of Panem, while legitimizing the social inequalities the wealthy Capitol works hard to immortalize. However, Katniss undergoes a metamorphosis through her discovery of her own identity, which hints at an emerging female empowerment. This transformation, together with her identification with the Mockingjay, a supernatural being that voices her beliefs and emotions, contributes to disrupting the status quo imposed by the almighty Gamemakers and to purveying a message of optimism.


Author(s):  
Luiz Tanajura ◽  
José Costa Júnior ◽  
Áurea Chaves ◽  
Marinella Centemero ◽  
Fausto Feres

Acute coronary syndromes are common situations in medical practice, with high morbidity and mortality. Consequent to its relevance, its clinical management has always been subject of discussion and controversy. Since the past decade, the dual antiplatelet regimen has been the main therapeutic option used in its passivation, whereas percutaneous interventions have become the most common therapeutic option. Clopidogrel, the drug initially used in combination with aspirin, is effective and safe; however, it has disadvantages that led to the development of a new generation of more efficient antiplatelet drugs, such as prasugrel and ticagrelor. In large comparative clinical trials, these two drugs proved superior to clopidogrel in reducing major combined cardiac events. Hence the main guidelines currently support the two new agents, which are considered first-line drugs. Due to the clear differences between the protocols of clinical trials corroborating their inclusion in clinical practice, it is not possible to make direct comparison without the risk of generating hasty impressions. More recently, a large prospective, randomized clinical trial provided an appropriate head-to-head comparison between prasugrel and ticagrelor in cases of acute coronary disease, in a population submitted to invasive treatment. The study demonstrated a significant advantage of prasugrel. In this review, we discuss the primary details of these more contemporary drugs and the most relevant clinical trials related to them, identifying the advantages and disadvantages of each agent. At the end, we state our view on their current prescription.


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