Evaluation of the Anti-Mycobacterial and Anti-Inflammatory Activities of the New Cardiotonic Steroid γ-Benzylidene Digoxin-15 in Macrophage Models of Infection

Microorganisms, Journal Year: 2025, Volume and Issue: 13(2), P. 269 - 269

Published: Jan. 25, 2025

Cardiotonic steroids modulate various aspects of the inflammatory response. The synthetic cardiotonic steroid γ-benzylidene digoxin 15 (BD-15), a derivative, has emerged as promising candidate with potential immunomodulatory effects. However, its biological activity remains largely unexplored. This study investigated anti-mycobacterial and anti-inflammatory effects BD-15 in an vitro macrophage infection model Mycobacterium spp. Unlike digoxin, which showed significant toxicity at higher concentrations, exhibited no cytotoxicity RAW 264.7 cells (a murine cell line). Both compounds were evaluated smegmatis-infected cells, reducing bacterial burden without direct bactericidal activity. Additionally, both modulated pro-inflammatory cytokine levels, notably by decreasing tumor necrosis factor alpha (TNF-α) interleukin-1 beta (IL-1β) levels. specifically reduced NOD-, LRR-, pyrin-domain-containing protein 3 (NLRP3) inflammasome expression increased interleukin-10 (IL-10) production. Notably, colony-forming unit (CFU) counts tuberculosis-infected cells. Toxicity assays HepG2 human liver cancer line) that had minimal hepatotoxicity compared to demonstrated negligible acute Artemia salina bioassay. These findings revealed highlighted safer alternative for therapeutic applications.

Language: Английский

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Regulations of malaria in children with human immunodeficiency virus infection: A review

Medicine, Journal Year: 2023, Volume and Issue: 102(46), P. e36166 - e36166

Published: Nov. 17, 2023

This comprehensive review explores the intricate relationship between 2 major global health challenges, malaria and HIV, with a specific focus on their impact children. These diseases, both endemic in sub-Saharan Africa, create dual burden that significantly elevates risk of morbidity mortality, particularly children compromised immune systems due to HIV. The delves into complex mechanisms by which these infections interact, from heightened clinical frequencies HIV-infected individuals potential antiretroviral therapy treatment. Different research engines were utilized writing this paper such as Web Science, Google Scholar, Pubmed Central, ResearchGate, Academia Edu. To address critical concern, study identifies discusses various regulatory treatment strategies. It emphasizes importance daily cotrimoxazole prophylaxis insecticide-treated nets preventing protease inhibitors mRNA-based vaccines innovative solutions is highlighted. Additionally, underscores significance climate data artificial intelligence improving diagnostics drug development. Furthermore, introduces concept genetically modified mosquitoes novel approach vector control, offering promising avenue protect HIV-positive mosquito-borne diseases like malaria. Through analysis strategies, aims provide foundation for policymakers, healthcare professionals, researchers develop effective regulations interventions reduce HIV children, public outcomes regions.

Language: Английский

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mRNA Technology in Modern Medicine: Review and Future Prospects

Deleted Journal, Journal Year: 2025, Volume and Issue: 2, P. 1 - 1

Published: Jan. 17, 2025

Messenger RNA (mRNA) technology has revolutionized modern medicine, particularly in developing vaccines and gene therapies. While its prominence soared during the COVID-19 pandemic, foundation was built on decades of meticulous research. This review explores historical evolution mRNA technology, stabilization delivery breakthroughs, applications combating infectious diseases, cancer, genetic disorders. The study utilized a systematic search peer-reviewed articles from leading databases such as PubMed Scopus, focusing advancements clinical applications. Future potential treating chronic enhancing immunotherapy, addressing public health emergencies is also discussed, emphasizing need for sustained research innovation to harness transformative capabilities fully.

Language: Английский

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Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Nov. 14, 2024

Abstract In the last decade, messenger ribonucleic acid (mRNA)-based drugs have gained great interest in both immunotherapy and non-immunogenic applications. This surge can be largely attributed to demonstration of distinct advantages offered by various mRNA molecules, alongside rapid advancements nucleic delivery systems. It is noteworthy that immunogenicity presents a double-edged sword. context immunotherapy, extra supplementation adjuvant generally required for induction robust immune responses. Conversely, non-immunotherapeutic scenarios, activation unwanted considering host tolerability high expression demand mRNA-encoded functional proteins. Herein, mainly focused on linear non-replicating mRNA, we overview preclinical clinical progress prospects medicines encompassing vaccines other therapeutics. We also highlight importance focusing host-specific variations, including age, gender, pathological condition, concurrent medication individual patient, maximized efficacy safety upon administration. Furthermore, deliberate potential challenges may encounter realm disease treatment, current endeavors improvement, as well application future advancements. Overall, this review aims present comprehensive understanding mRNA-based therapies while illuminating prospective development drugs.

Language: Английский

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Types of RNA therapeutics

Progress in molecular biology and translational science, Journal Year: 2024, Volume and Issue: unknown, P. 41 - 63

Published: Jan. 1, 2024

Language: Английский

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mRNA-based vaccines – global approach, challenges, and could be a promising wayout for future pandemics

Pharmaceutical Development and Technology, Journal Year: 2024, Volume and Issue: 29(6), P. 559 - 565

Published: May 30, 2024

mRNA-based vaccines are assured to significantly boost biopharmaceuticals since outbreak of coronavirus disease- 2019. Respiratory infections, such as influenza, SARS, MERS, COVID-19, and respiratory syncytial virus, often have high transmission rates due their airborne spread. infections can lead severe illness death. These outbreaks cause substantial economic social disruption, seen with the COVID-19 pandemic. In our interconnected world, diseases spread rapidly across borders. (e.g., mRNA-1283) reduce by creating immunity in population, thus lowering incidence these diseases. Vaccines crucial for global health security, helping prevent local from becoming pandemics. Nevertheless, various concerns remain intracellular delivery, susceptibility degradation catalytic hydrolysis, instability several physiological conditions. Therefore, an hour needed address challenges opportunities attaining high-quality stable novel drug delivery systems. The authors contributed extensive review clinical development, progress stability mitigate market needs. addition, discuss advances growth date; which dominate scope therapeutic implementation. Finally, recent trials, adjuvant benefits, prospects discussed.

Language: Английский

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Next-Generation Vaccine Development with Nanomaterials: Recent Advances, Possibilities, and Challenges

Annual Review of Biomedical Engineering, Journal Year: 2024, Volume and Issue: 26(1), P. 273 - 306

Published: July 3, 2024

Nanomaterials are becoming important tools for vaccine development owing to their tunable and adaptable nature. Unique properties of nanomaterials afford opportunities modulate trafficking through various tissues, complement or augment adjuvant activities, specify antigen valency display. This versatility has enabled recent work designing nanomaterial vaccines a broad range diseases, including cancer, inflammatory infectious diseases. Recent successes nanoparticle during the coronavirus disease 2019 (COVID-19) pandemic have fueled enthusiasm further. In this review, most developments in nanovaccines disease, allergic nanoadjuvants summarized. Additionally, challenges clinical translation unique class materials discussed.

Language: Английский

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Optimizing antigen selection for the development of tuberculosis vaccines

Cell Insight, Journal Year: 2024, Volume and Issue: 3(3), P. 100163 - 100163

Published: March 16, 2024

Tuberculosis (TB) remains a prevalent global infectious disease caused by genetically closely related tubercle bacilli in

Language: Английский

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Peptide and m-RNA Vaccines: Peculiarities of Immunogenicity and Protective Effect

Epidemiology and Vaccinal Prevention, Journal Year: 2025, Volume and Issue: 23(6), P. 137 - 146

Published: Jan. 15, 2025

Relevance . Pandemic pathogen variants formation is a pressing issue of modern healthcare system thus classic approaches preventive measures against infectious diseases require revision including implementation effective, safe, universal and rapid methods vaccine production. Aim To conduct analysis scientific literature concerning peculiarities m-RNA peptide vaccines. Search publications was carried out in PubMed, Google Scholar e-library databases. Conclusions In addition to obvious advantages both platforms have disadvantages. vaccines are thermally unstable need be stored transported at temperature not exceeding minus 80 °C which significantly reduces their availability countries with low income. platform chosen manufacture SARS-CoV-2 Western (USA Germany) during the COVID-19 pandemic despite mentioned disadvantage. Most perspective mRNA prototypes were designed combat influenza, respiratory syncytial virus, rabies, malaria, HIV, Ebola Zika virus cytomegalovirus. Peptide undemanding external factors such as storage transportation. On other hand, they more immunogenic achieved by adding various adjuvants. They also challenging due complexity quaternary structure protein epitopes antigens. date, foreign HIV infection, hepatitis C, tuberculosis, leishmaniasis passed first second stages clinical trials. Both undergo degradation human body, prompts scientists develop new molecular for delivering matrix target cells

Language: Английский

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Novel mRNA vaccines induce potent immunogenicity and afford protection against tuberculosis

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 13, 2025

Introduction Mycobacterium tuberculosis ( Mtb ) is the causative agent of (TB), a disease with severe global burden. The intractability has prevented identification clear correlates protection against TB and hindered development novel vaccines that are urgently required. Lipid nanoparticle (LNP)-formulated mRNA highly promising vaccine platform yet to be thoroughly applied TB. Methods We selected five antigens (PPE15, ESAT6, EspC, EsxI, MetE) evaluated their potential as LNP-formulated vaccines, both when each antigen was delivered individually, all were combined in mix regimen (m-Mix). Results Each construct demonstrated unique cellular humoral immunogenicity, m-Mix, well single conferred significant murine challenge model. Whilst potent immune responses maintained boost BCG, there no additional increase efficacy BCG. Combination m-Mix recombinant, replication-deficient chimpanzee adenovirus (ChAdOx1), heterologous prime-boost delivery (C-m-Mix), appeared result increased upon infection, than either alone. Discussion This work warrants further investigation for TB, whilst indicating C-m-Mix progress stages development.

Language: Английский

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