Probiotic comes to the rescue of blood-stage Plasmodium infection: Probiotic Bifidobacterium adolescentis IM38 decreases the expression of CTLA-4, PD-L1 and LAG-3, promotes CD4+ T-cell function, increases secretion of protective antibodies, promotes and clears blood-stage malaria, via up regulation of its target gene, 28/February/2019, 7.26 am

Probiotics-based adjunctive therapy for Malaria: A probiotic mixture(LB+LC) encompassing Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601 increases Ferroportin expression, decreases intracellular iron accumulation, inhibits cellular damage, prevents hemolysis, and inhibits malaria infection, via upregulation of its target gene, 28/February/2019, 7.04 am
February 28, 2019
Combinatorial anti-cancer therapy targeting CDK4/6 pathway and immune receptors enhances the efficacy of Cancer immunotherapy: A pharmacological mixture encompassing  Metformin, Navitoclax/ABT-263, Dasatinib and 2-Deoxy-d-glucose (MNDDG)  inhibits the expression of cell cycle protein CDK4/CDK6, increases levels of T-III IFNs, inhibits the proliferation of Treg cells, decreases DNMT1 expression, inhibits the expression of a number of immune evasion molecules, increases antigen presentation and unfolding response, increases Cytotoxic activity of T-cells, decreases tumor burden and increases survival via up-regulation of its target genes, 28/February/2019, 7.39 am
February 28, 2019
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National Science day special

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We wish everyone a very happy national science day. On this special occasion, we are happy to announce that Bio-Med/Pharma/Therapeutic/Clinical ideas posted today (28/February/2019) will be available to the use of Scientists/Professors/Faculties/Teachers/Physicians/Researchers for free. So, there will be no terms and conditions for the ideas posted today. Each idea posted will be served first come, first serve basis. Write to admin@genomediscovery.org for more details.

Dr L Boominathan PhD

President, Director & CSO, GBMD.

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Introduction: What they say

A study from the Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA shows thatRegulatory T cells impede acute and long-term immunity to blood-stage malaria through CTLA-4.” This research paper was published, in September 2017 issue of the journal “Nature Medicine” [One of the best research journals in General biology with an I.F of 28.710], by Prof. Harty J and his research team members.

In connection with the study presented above, Prof. Harty J’s research team members had earlier shown that “Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection.” This research paper was published in December 2011 issue of the journal Nature Immunology” [One of the best research journals in General biology with an I.F of 28.710].


What we say:

On the foundation of these interesting findings, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Probiotic comes to the rescue of blood-stage Plasmodium infection: Probiotic Bifidobacterium adolescentis IM38 decreases the expression of CTLA-4, PD-L1 and LAG-3, promotes CD4+ T-cell function, increases secretion of protective antibodies, promotes and clears blood-stage malaria, via up regulation of its target gene


From significance of the study to Public health relevance:

Given that: (1) 214 million new cases of malaria had been reported in 2015; (2) nearly 438,000 people out of 214 million people who were infected with Malaria had died in 2015; (3) malaria has the potential to affect nearly half the global population; (4) molecular pathways involved and the mechanism of development of drug-resistant malaria are far from understood; (4) treating drug-resistant malaria is still a daunting task; (5) millions of deaths occur due to malaria every year; (6) out of the 125 million international travellers who visit countries, such as Ivory Coast, Angola, Burkina Faso, Burkina Faso, Mozambique and Mali, more than 30, 000 contract the disease; (7) most of the malaria cases are registered in developing countries, such as sub-Saharan Africa—that cannot afford high-cost required for the treatment of drug-resistant malaria—,compared to developed countries, such as US (10,000 malaria cases/ per year) and UK (1,500 malaria cases/year), (8) humans could not mount immunity against blood stage-malaria; and prevent re-infections; (9) billions of dollars are being spent each year globally for the treatment of Malaria, there is an urgent need to find: (i) a way to inhibit drug-resistant malaria; and (ii) a side-effect-free-Natural product-based drug that prevents relapse/recurrence of blood-stage/drug-resistant Malaria.


What is known?

Prof. Hardy’s research team has shown that blockade of CTLA-4, PD-1 ligand PD-L1 and the inhibitory receptor LAG-3: a) promote CD4+ T-cell function; b) increase the number of follicular helper T cells, germinal-center B cells etc.,; c) enhance the levels of protective antibodies; d) augment parasite clearance; e) promote species-transcending immunity to blood-stage malaria; f) prevent reinfection through potentiation of adaptive immunity; and g) clear blood-stage malaria, suggesting that inhibiting the expression of immune evasion molecules, such as CTLA-4, PD-1, PD-L1 and LAG-3, may attenuate chronic malaria-driven T-cell dysfunction; and promote parasite clearance in blood-stage malaria.


From research findings to Therapeutic opportunity:

This study suggests, for the first time, that Probiotic Bifidobacterium adolescentis IM38  may aid in the treatment of blood-stage malaria. Probiotic Bifidobacterium adolescentis IM38, by increasing the expression of its target gene, it may decrease the expression of immune evasion molecules, such as CTLA-4, PD-1, PD-L1 and LAG-3 (Figure 1). Thereby, it may: (1) increase CD4+ T-cell function; (2) augment the number of helper T cells, germinal-center B cells etc.,; (3) increase secretion of protective antibodies; (4) promote plasmodium parasite clearance; (5) mount acute and long-term immunity to blood-stage malaria; (6) stifle reinfection through induction of adaptive immunity;(7) clear blood-stage malaria

Figure 1 Mechanistic insights into how Probiotic Bifidobacterium adolescentis IM38 inhibits blood stage malaria. Probiotic Bifidobacterium adolescentis IM38 inhibits the expression of CTLA-4, PD-1, PD-L1 and LAG-3 via up regulation of its target genes

Figure 2. Probiotic Bifidobacterium adolescentis IM38 may function as an anti-malarial agent through down regulation of PD-L1, CT-LA4 and LAG3

Thus, pharmacological formulations encompassing “Probiotic Bifidobacterium adolescentis IM38, either alone or in combination with other antimalarial drugs,” may be used to treat blood-stage malaria (Figures 1-2).  Given the non-toxic and inexpensive nature of Probiotic Bacillus subtillis B10 compared to other anti-malarial agents, it may be an agent of choice to treat malaria.

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Details of the research findings:

Undisclosed mechanistic information: How does Probiotic Bifidobacterium adolescentis IM38 decrease the expression of CTLA-4, PD-1, PD-L1 and LAG-3?

Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Amount: $750#

For payment and purchase details, you may reach us at admin@genomediscovery.org

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References:

Web: http://genomediscovery.org or http://newbioideas.com

Citation: Boominathan, L.,  Probiotic comes to the rescue of blood-stage Plasmodium infection: Probiotic Bifidobacterium adolescentis IM38 decreases the expression of CTLA-4, PD-L1 and LAG-3, promotes CD4+ T-cell function, increases secretion of protective antibodies, promotes and clears blood-stage malaria, via up regulation of its target gene, 28/February/2019, 7.25 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

Courtesy: When you cite, drop us a line at admin@genomediscovery.org

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