scholarly journals Multiplexed Microsphere-Based Flow Cytometric Assay to Assess Strain Transcending Antibodies to Plasmodium vivax Duffy Binding Protein II Reveals an Efficient Tool to Identify Binding-Inhibitory Antibody Responders

2021 ◽  
Vol 12 ◽  
Author(s):  
Jéssica R. S. Alves ◽  
Fernanda F. de Araújo ◽  
Camilla V. Pires ◽  
Andréa Teixeira-Carvalho ◽  
Barbara A. S. Lima ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Binding Protein ◽  
Public Health Problem ◽  
Multiplex Assay ◽  
Major Public Health Problem ◽  
Flow Cytometric Assay ◽  
Inhibitory Antibody ◽  
Duffy Binding Protein ◽  
Flow Cytometric

Malaria remains a major public health problem worldwide, and Plasmodium vivax is the most widely distributed malaria parasite. Naturally acquired binding inhibitory antibodies (BIAbs) to region II of the Duffy binding protein (DBPII), a P. vivax ligand that is critical for reticulocyte invasion, are associated with a reduced risk of clinical malaria. Owing to methodological issues in evaluating antibodies that inhibit the DBPII–DARC interaction, a limited number of studies have investigated DBPII BIAbs in P. vivax-exposed populations. Based on the assumption that individuals with a consistent BIAb response are characterized by strain-transcending immune responses, we hypothesized that detecting broadly reactive DBPII antibodies would indicate the presence of BIAb response. By taking advantage of an engineered DBPII immunogen targeting conserved DBPII neutralizing epitopes (DEKnull-2), we standardized a multiplex flow cytometry-based serological assay to detect broadly neutralizing IgG antibodies. For this study, a standard in vitro cytoadherence assay with COS-7 cells expressing DBPII was used to test for DBPII BIAb response in long-term P. vivax-exposed Amazonian individuals. Taken together, the results demonstrate that this DBPII-based multiplex assay facilitates identifying DBPII BIAb carriers. Of relevance, the ability of the multiplex assay to identify BIAb responders was highly accurate when the positivity for all antigens was considered. In conclusion, the standardized DBPII-based flow cytometric assay confirmed that DBPII-BIAb activity was associated with the breadth rather than the magnitude of anti-DBPII antibodies. Altogether, our results suggest that multiplex detection of broadly DBPII-reactive antibodies facilitates preliminary screening of BIAb responders.

scholarly journals Identification of an Immunogenic Broadly Inhibitory Surface Epitope of thePlasmodium vivaxDuffy Binding Protein Ligand Domain

mSphere ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Miriam T. George ◽  
Jesse L. Schloegel ◽  
Francis B. Ntumngia ◽  
Samantha J. Barnes ◽  
Christopher L. King ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Vaccine Candidate ◽  
Allelic Variation ◽  
Binding Protein ◽  
Effective Vaccine ◽  
Inhibitory Antibody ◽  
Duffy Binding Protein ◽  
Content Type ◽  
Surface Receptor

ABSTRACTThePlasmodium vivaxDuffy binding protein region II (DBPII) is a vital ligand for the parasite’s invasion of reticulocytes, thereby making this molecule an attractive vaccine candidate against vivax malaria. However, strain-specific immunity due to DBPII allelic variation in Bc epitopes may complicate vaccine efficacy, suggesting that an effective DBPII vaccine needs to target conserved epitopes that are potential targets of strain-transcending neutralizing immunity. The minimal epitopes reactive with functionally inhibitory anti-DBPII monoclonal antibody (MAb) 3C9 and noninhibitory anti-DBPII MAb 3D10 were mapped using phage display expression libraries, since previous attempts to deduce the 3C9 epitope by cocrystallographic methods failed. Inhibitory MAb 3C9 binds to a conserved conformation-dependent epitope in subdomain 3, while noninhibitory MAb 3D10 binds to a linear epitope in subdomain 1 of DBPII, consistent with previous studies. Immunogenicity studies using synthetic linear peptides of the minimal epitopes determined that the 3C9 epitope, but not the 3D10 epitope, could induce functionally inhibitory anti-DBPII antibodies. Therefore, the highly conserved binding-inhibitory 3C9 epitope offers the potential as a component in a broadly inhibitory, strain-transcending DBP subunit vaccine.IMPORTANCEVivax malaria is the second leading cause of malaria worldwide and the major cause of non-African malaria. Unfortunately, efforts to develop antimalarial vaccines specifically targetingPlasmodium vivaxhave been largely neglected, and few candidates have progressed into clinical trials. The Duffy binding protein is considered a leading blood-stage vaccine candidate because this ligand’s recognition of the Duffy blood group reticulocyte surface receptor is considered essential for infection. This study identifies a new target epitope on the ligand’s surface that may serve as the target of vaccine-induced binding-inhibitory antibody (BIAb). Understanding the potential targets of vaccine protection will be important for development of an effective vaccine.

Medicinal Plants and Bioactive Compounds for Diabetes Management: Important Advances for Drug Discovery

2020 ◽  
Vol 26 ◽  
Author(s):  
Kondeti Ramudu Shanmugam ◽  
Bhasha Shanmugam ◽  
Gangigunta Venkatasubbaiah ◽  
Sahukari Ravi ◽  
Kesireddy Sathyavelu Reddy
Keyword(s):  
Herbal Medicine ◽  
Medicinal Plants ◽  
Bioactive Compounds ◽  
Diabetes Management ◽  
Therapeutic Potential ◽  
Public Health Problem ◽  
In Vivo Studies ◽  
Major Public Health Problem

Background : Diabetes is a major public health problem in the world. It affects each and every part of the human body and also leads to organ failure. Hence, great progress made in the field of herbal medicine and diabetic research. Objectives: Our review will focus on the effect of bioactive compounds of medicinal plants which are used to treat diabetes in India and other countries. Methods: Information regarding diabetes, oxidative stress, medicinal plants and bioactive compounds were collected from different search engines like Science direct, Springer, Wiley online library, Taylor and francis, Bentham Science, Pubmed and Google scholar. Data was analyzed and summarized in the review. Results and Conclusion: Anti-diabetic drugs that are in use have many side effects on vital organs like heart, liver, kidney and brain. There is an urgent need for alternative medicine to treat diabetes and their disorders. In India and other countries herbal medicine was used to treat diabetes. Many herbal plants have antidiabetic effects. The plants like ginger, phyllanthus, curcumin, aswagandha, aloe, hibiscus and curcuma showed significant anti-hyperglycemic activities in experimental models and humans. The bioactive compounds like Allicin, azadirachtin, cajanin, curcumin, querceitin, gingerol possesses anti-diabetic, antioxidant and other pharmacological properties. This review focuses on the role of bioactive compounds of medicinal plants in prevention and management of diabetes. Conclusion: Moreover, our review suggests that bioactive compounds have the potential therapeutic potential against diabetes. However, further in vitro and in vivo studies are needed to validate these findings.

scholarly journals Microwave-Assisted Synthesis of (Piperidin-1-yl)quinolin-3-yl)methylene)hydrazinecarbothioamides as Potent Inhibitors of Cholinesterases: A Biochemical and In Silico Approach

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 656
Author(s):  
Rubina Munir ◽  
Muhammad Zia-ur-Rehman ◽  
Shahzad Murtaza ◽  
Sumera Zaib ◽  
Noman Javid ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Critical Role ◽  
Public Health Problem ◽  
Microwave Assisted Synthesis ◽  
Major Public Health Problem ◽  
Spectroscopic Techniques ◽  
Dual Inhibitor ◽  
Microwave Assisted ◽  
Ic50 Values

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, characterized by central cognitive dysfunction, memory loss, and intellectual decline poses a major public health problem affecting millions of people around the globe. Despite several clinically approved drugs and development of anti-Alzheimer’s heterocyclic structural leads, the treatment of AD requires safer hybrid therapeutics with characteristic structural and biochemical properties. In this endeavor, we herein report a microwave-assisted synthesis of a library of quinoline thiosemicarbazones endowed with a piperidine moiety, achieved via the condensation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes and (un)substituted thiosemicarbazides. The target N-heterocyclic products were isolated in excellent yields. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). Anti-Alzheimer potential of the synthesized heterocyclic compounds was evaluated using acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The in vitro biochemical assay results revealed several compounds as potent inhibitors of both enzymes. Among them, five compounds exhibited IC50 values less than 20 μM. N-(3-chlorophenyl)-2-((8-methyl-2-(piperidin-1-yl)quinolin-3-yl)methylene)hydrazine carbothioamide emerged as the most potent dual inhibitor of AChE and BChE with IC50 values of 9.68 and 11.59 μM, respectively. Various informative structure–activity relationship (SAR) analyses were also concluded indicating the critical role of substitution pattern on the inhibitory efficacy of the tested derivatives. In vitro results were further validated through molecular docking analysis where interactive behavior of the potent inhibitors within the active pocket of enzymes was established. Quinoline thiosemicarbazones were also tested for their cytotoxicity using MTT assay against HepG2 cells. Among the 26 novel compounds, there were five cytotoxical and 18 showed proliferative properties.

scholarly journals Non-Toxic Virucidal Macromolecules Show High Efficacy Against Influenza Virus Ex Vivo and In Vivo

2020 ◽  
Author(s):  
Ozgun Kocabiyik ◽  
Valeria Cagno ◽  
Paulo Jacob Silva ◽  
Yong Zhu ◽  
Laura Sedano ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Viral Infections ◽  
Ex Vivo ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
New Class ◽  
Influenza Strain ◽  
Low Toxicity

AbstractInfluenza is one of the most widespread viral infections worldwide and represents a major public health problem. The risk that one of the next pandemics is caused by an influenza strain is very high. It is very important to develop broad-spectrum influenza antivirals to be ready for any possible vaccine shortcomings. Anti-influenza drugs are available but they are far from ideal. Arguably, an ideal antiviral should target conserved viral domains and be virucidal, i.e. irreversibly inhibit viral infectivity. Here, we describe a new class of broad-spectrum anti-influenza macromolecules that meets these criteria and displays exceedingly low toxicity. These compounds are based on a cyclodextrin core modified on its primary face with long hydrophobic linkers terminated in 6’sialyl-N-acetyllactosamine (6’SLN) or 3’SLN. SLN enables nanomolar inhibition of the viruses while the hydrophobic linkers confer irreversibility to the inhibition. The combination of these two properties allows for efficacy in vitro against several human or avian influenza strains, as well as against a 2009 pandemic influenza strain ex vivo. Importantly, we show that, in mice, the compounds provide therapeutic efficacy when administered 24h post-infection allowing 90% survival as opposed to no survival for the placebo and oseltamivir..

scholarly journals Antimalarial Activities of Peptide Antibiotics Isolated from Fungi

2001 ◽  
Vol 45 (1) ◽  
pp. 145-149 ◽  
Author(s):  
G. Nagaraj ◽  
M. V. Uma ◽  
M. S. Shivayogi ◽  
Hemalatha Balaram
Keyword(s):  
High Performance ◽  
Public Health Problem ◽  
Chemotherapeutic Agents ◽  
Major Public Health Problem ◽  
Drug Resistant ◽  
Peptide Antibiotics ◽  
Mass Spectral Analysis ◽  
Mass Spectral ◽  
Micromolar Range

ABSTRACT Malaria caused by Plasmodium falciparum is a major public health problem in the developing countries of the world. Clinical treatment of malaria has become complicated due to the occurrence of infections caused by drug resistant parasites. Secondary metabolites from fungi are an attractive source of chemotherapeutic agents. This work reports the isolation and in vitro antiplasmodial activities of peptide antibiotics of fungal origin. The three peptide antibiotics used in this study were efrapeptins, zervamicins, and antiamoebin. The high-performance liquid chromatography-purified peptides were characterized by nuclear magnetic resonance and mass spectral analysis. All three fungal peptides kill P. falciparum in culture with 50% inhibitory concentrations in the micromolar range. A possible mode of action of these peptide antibiotics on P. falciparum is presented.

Development of new dinuclear Fe(III) coordination compounds with in vitro nanomolar antitrypanosomal activity

2021 ◽  
Author(s):  
Felipe Figuerôa Moreira ◽  
Juliana de Araujo Portes ◽  
Nathalia Florencia Barros Azeredo ◽  
Christiane Fernandes ◽  
Adolfo Horn ◽  
...  
Keyword(s):  
Public Health ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Health Problem ◽  
Coordination Compounds ◽  
Public Health Problem ◽  
Neglected Tropical Disease ◽  
Major Public Health Problem ◽  
Protozoan Pathogen

Chagas disease is a neglected tropical disease caused by the protozoan pathogen Trypanosoma cruzi. The disease is the major public health problem affecting about 6 to 7 million people worldwide,...

scholarly journals Platelet-Rich Plasma Improves the Wound Healing Potential of Mesenchymal Stem Cells through Paracrine and Metabolism Alterations

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Barbara Hersant ◽  
Mounia Sid-Ahmed ◽  
Laura Braud ◽  
Maud Jourdan ◽  
Yasmine Baba-Amer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Platelet Rich Plasma ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Dependent Manner ◽  
Safe Alternative

Chronic and acute nonhealing wounds represent a major public health problem, and replacement of cutaneous lesions by the newly regenerated skin is challenging. Mesenchymal stem cells (MSC) and platelet-rich plasma (PRP) were separately tested in the attempt to regenerate the lost skin. However, these treatments often remained inefficient to achieve complete wound healing. Additional studies suggested that PRP could be used in combination with MSC to improve the cell therapy efficacy for tissue repair. However, systematic studies related to the effects of PRP on MSC properties and their ability to rebuild skin barrier are lacking. We evaluated in a mouse exhibiting 4 full-thickness wounds, the skin repair ability of a treatment combining human adipose-derived MSC and human PRP by comparison to treatment with saline solution, PRP alone, or MSC alone. Wound healing in these animals was measured at day 3, day 7, and day 10. In addition, we examined in vitro and in vivo whether PRP alters in MSC their proangiogenic properties, their survival, and their proliferation. We showed that PRP improved the efficacy of engrafted MSC to replace lost skin in mice by accelerating the wound healing processes and ameliorating the elasticity of the newly regenerated skin. In addition, we found that PRP treatment stimulated in vitro, in a dose-dependent manner, the proangiogenic potential of MSC through enhanced secretion of soluble factors like VEGF and SDF-1. Moreover, PRP treatment ameliorated the survival and activated the proliferation of in vitro cultured MSC and that these effects were accompanied by an alteration of the MSC energetic metabolism including oxygen consumption rate and mitochondrial ATP production. Similar observations were found in vivo following combined administration of PRP and MSC into mouse wounds. In conclusion, our study strengthens that the use of PRP in combination with MSC might be a safe alternative to aid wound healing.

Evaluation of immune responses elicited in mice against a recombinant malaria vaccine based on Plasmodium vivax Duffy binding protein

Vaccine ◽  
2004 ◽  
Vol 22 (27-28) ◽  
pp. 3727-3737 ◽  
Author(s):  
Syed Shams Yazdani ◽  
Ahmad Rushdi Shakri ◽  
Paushali Mukherjee ◽  
Sanjeev Kumar Baniwal ◽  
Chetan E. Chitnis
Keyword(s):  
Immune Responses ◽  
Plasmodium Vivax ◽  
Malaria Vaccine ◽  
Binding Protein ◽  
Duffy Binding Protein

scholarly journals Effect of Different Terpene-Containing Essential Oils on the Proliferation ofEchinococcus granulosusLarval Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Clara María Albani ◽  
Guillermo María Denegri ◽  
María Celina Elissondo
Keyword(s):  
Essential Oils ◽  
Effective Means ◽  
Control Cell ◽  
Larval Growth ◽  
Public Health Problem ◽  
Mentha Piperita ◽  
Major Public Health Problem ◽  
Isolated Cells ◽  
Vitro Effect

Human cystic echinococcosis remains a major public health problem on several countries and the treatment strategies are not solved. The aim of the present work was to determine the in vitro effect of thymol andMentha piperita,M. pulegium,andRosmarinus officinalisessential oils on the proliferation ofE. granulosuslarval cells. Isolated cells and cellular aggregates were obtained from hydatid cyst’s germinal layer and exposed to 1, 5, and 10 μg/ml of thymol and the different essential oils for 7 days. Drug effect was evaluated using test viability and scanning electron microscopy. Control cell culture viability was 2.1 x 106(100%) after 7 days of incubation. At day 7, thymol 5 μg/ml caused a reduction in cell viability of 63% and the essential oils ofM. piperita10 μg/ml,M. pulegium10 μg/ml, andR. officinalis10 μg/ml produced a reduction in the viability of 77, 82, and 71%, respectively. Moreover essential oils caused reduction in cell number, collapsed cells, and loss of normal tridimensional composition of the aggregates. Due to the inhibitory effect caused by essential oils onE. granulosuscells we suggested that it would be an effective means for suppression of larval growth.

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