General Characteristics of Adjuvants and Their Mechanism of Action (Part 1)

One of priority issues of the present-day healthcare system is development of new vaccines and improvement of existing ones due to decreasing immunocompetence of the population, emergence of new infections and reemergence of old ones which were previously thought to be under control. Adjuvants have proven to be integral and important components of modern vaccines, as they enhance immune response to the vaccine antigen. However, despite a lot of effort put into their development, only a small number of adjuvants are currently used in clinical practice.The aim of the study was to systematise literature data on the adjuvants’ mechanisms of action, their specific structure, composition, and stimulation effects that mediate their immunoadjuvant properties. The paper summarises data on adjuvants used as components in licensed vaccines, describes their characteristics, analyses molecular mechanisms of their action in order to establish correlation between their structure and activity, which is important for the development of more efficacious and safe adjuvants. The paper cites advanced developments aimed at enhancing stimulation effects of existing adjuvants. It concludes by stating that the key research area aimed at improving vaccination efficacy is the study of mechanisms that contribute to the development of effective protection against infectious agents, as well as analysis of how to use adjuvants to stimulate the body’s defensive mechanisms, primarily by impacting the innate immunity.

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General characteristics of adjuvants and their mechanisms of action (part 2)

BIOpreparations Prevention Diagnosis Treatment ◽

10.30895/2221-996x-2021-21-1-20-30 ◽

2021 ◽

Vol 21 (1) ◽

pp. 20-30

Author(s):

N. А. Alpatova ◽

Zh. I. Avdeeva ◽

S. L. Lysikova ◽

O. V. Golovinskaya ◽

L. A. Gayderova ◽

...

Keyword(s):

Vaccine Development ◽

Mechanisms Of Action ◽

Vaccine Adjuvants ◽

Efficacy And Safety ◽

Subunit Vaccines ◽

Public Health Challenges ◽

Efficient Induction ◽

Is Development ◽

Effective Use ◽

New Vaccines

One of the major public health challenges today is development of new vaccines and technologies to optimize the vaccination process. There is a growing scientific interest in vaccine adjuvants that enhance vaccine immunogenicity. At present, numerous studies are underway to develop COVID-19 vaccines, including inactivated and subunit vaccines which contain adjuvants for efficient induction of immune response and solid immunity. The aim of the study was to systematise literature related to the analysis of the structure, mechanisms of action and stimulating properties of vaccine adjuvants (synthetic oligodeoxynucleotides, virosomes, polyoxidonium, sovidone), as well as to summarise data on the effects of adjuvants used in SARS-CoV, MERS-CoV, and SARS-CoV-2 vaccine development studies. The paper analyses the prospects for enhancing the stimulating effect of the adjuvants when used in combination with compounds having a different mechanism of action. It also analyses the results of studies of adjuvanted vaccines against SARS-CoV and MERS-CoV, which may be useful when selecting adjuvants with optimal efficacy and safety profiles to be used in SARS-CoV-2 vaccines under development. It was concluded that understanding of the mechanisms of action of adjuvants that mediate their stimulating effect on the body’s immune system will contribute to safe and effective use of adjuvants to enhance the immunogenicity of both authorised and new vaccines.

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Cellular and Molecular Mechanisms of Action of Mitochondria-Targeted Antioxidants

Current Aging Science ◽

10.2174/1874609809666160921113706 ◽

2017 ◽

Vol 10 (1) ◽

pp. 41-48 ◽

Cited By ~ 34

Author(s):

Boris A. Feniouk ◽

Vladimir P. Skulachev

Keyword(s):

Molecular Mechanisms ◽

Mechanisms Of Action

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The correlation between lncRNAs and Helicobacter pylori in gastric cancer

Pathogens and Disease ◽

10.1093/femspd/ftaa004 ◽

2019 ◽

Vol 77 (9) ◽

Author(s):

Narges Dastmalchi ◽

Seyed Mahdi Banan Khojasteh ◽

Mirsaed Miri Nargesi ◽

Reza Safaralizadeh

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Molecular Mechanisms ◽

Gastrointestinal Diseases ◽

Mechanisms Of Action ◽

Molecular Pathways ◽

Gastric Diseases ◽

Non Coding Rnas ◽

H Pylori ◽

The Relationship

ABSTRACT Helicobacter pylori infection performs a key role in gastric tumorigenesis. Long non-coding RNAs (lncRNAs) have demonstrated a great potential to be regarded as effective malignancy biomarkers for various gastrointestinal diseases including gastric cancer (GC). The present review highlights the relationship between lncRNAs and H. pylori in GC. Several studies have examined not only the involvement of lncRNAs in H. pylori-associated GC progression but also their molecular mechanisms of action. Among the pertinent studies, some have addressed the effects of H. pylori infection on modulatory networks of lncRNAs, while others have evaluated the effects of changes in the expression level of lncRNAs in H. pylori-associated gastric diseases, especially GC. The relationship between lncRNAs and H. pylori was found to be modulated by various molecular pathways.

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Propolis Extract and Its Bioactive Compounds—From Traditional to Modern Extraction Technologies

Molecules ◽

10.3390/molecules26102930 ◽

2021 ◽

Vol 26 (10) ◽

pp. 2930

Author(s):

Jelena Šuran ◽

Ivica Cepanec ◽

Tomislav Mašek ◽

Božo Radić ◽

Saša Radić ◽

...

Keyword(s):

Antimicrobial Activity ◽

Geographical Origin ◽

Research Area ◽

Mechanisms Of Action ◽

Bioactive Molecules ◽

Erk Pathway ◽

Pharmacological Effects ◽

Propolis Extract ◽

Open Research ◽

Antioxidant Mechanisms

Propolis is a honeybee product known for its antioxidant, anti-inflammatory, anticancer, and antimicrobial effects. It is rich in bioactive molecules whose content varies depending on the botanical and geographical origin of propolis. These bioactive molecules have been studied individually and as a part of propolis extracts, as they can be used as representative markers for propolis standardization. Here, we compare the pharmacological effects of representative polyphenols and whole propolis extracts. Based on the literature data, polyphenols and extracts act by suppressing similar targets, from pro-inflammatory TNF/NF-κB to the pro-proliferative MAPK/ERK pathway. In addition, they activate similar antioxidant mechanisms of action, like Nrf2-ARE intracellular antioxidant pathway, and they all have antimicrobial activity. These similarities do not imply that we should attribute the action of propolis solely to the most representative compounds. Moreover, its pharmacological effects will depend on the efficacy of these compounds’ extraction. Thus, we also give an overview of different propolis extraction technologies, from traditional to modern ones, which are environmentally friendlier. These technologies belong to an open research area that needs further effective solutions in terms of well-standardized liquid and solid extracts, which would be reliable in their pharmacological effects, environmentally friendly, and sustainable for production.

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Gene Transcription as a Therapeutic Target in Leukemia

International Journal of Molecular Sciences ◽

10.3390/ijms22147340 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7340

Author(s):

Alvina I. Khamidullina ◽

Ekaterina A. Varlamova ◽

Nour Alhuda Hammoud ◽

Margarita A. Yastrebova ◽

Alexandra V. Bruter

Keyword(s):

Gene Transcription ◽

Molecular Mechanisms ◽

Hematological Malignancies ◽

Mechanisms Of Action ◽

Special Program ◽

Cell Plasticity ◽

Hematopoietic Stem ◽

Promising Strategy ◽

Tumor Cell Plasticity ◽

Transcriptional Landscape

Blood malignancies often arise from undifferentiated hematopoietic stem cells or partially differentiated stem-like cells. A tight balance of multipotency and differentiation, cell division, and quiescence underlying normal hematopoiesis requires a special program governed by the transcriptional machinery. Acquisition of drug resistance by tumor cells also involves reprogramming of their transcriptional landscape. Limiting tumor cell plasticity by disabling reprogramming of the gene transcription is a promising strategy for improvement of treatment outcomes. Herein, we review the molecular mechanisms of action of transcription-targeted drugs in hematological malignancies (largely in leukemia) with particular respect to the results of clinical trials.

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Agonist Lock Touched and Untouched Retinoic Acid Receptor-Related Orphan Receptor-γt (RORγt) Inverse Agonists: Classification Based on the Molecular Mechanisms of Action

Journal of Medicinal Chemistry ◽

10.1021/acs.jmedchem.0c02178 ◽

2021 ◽

Author(s):

Nannan Sun ◽

Qiong Xie ◽

Yongjun Dang ◽

Yonghui Wang

Keyword(s):

Retinoic Acid ◽

Molecular Mechanisms ◽

Retinoic Acid Receptor ◽

Mechanisms Of Action ◽

Orphan Receptor ◽

Inverse Agonists ◽

Acid Receptor

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The Emerging Role of Extracellular Vesicles in Endocrine Resistant Breast Cancer

Cancers ◽

10.3390/cancers13051160 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1160

Author(s):

Giusi La Camera ◽

Luca Gelsomino ◽

Amanda Caruso ◽

Salvatore Panza ◽

Ines Barone ◽

...

Keyword(s):

Breast Cancer ◽

Endocrine Therapy ◽

Extracellular Vesicles ◽

Molecular Mechanisms ◽

Endocrine Resistance ◽

Disease Recurrence ◽

Estrogen Receptor Α ◽

Research Area ◽

Tumor Evolution

Breast cancer is the most common solid malignancy diagnosed in females worldwide, and approximately 70% of these tumors express estrogen receptor α (ERα), the main biomarker of endocrine therapy. Unfortunately, despite the use of long-term anti-hormone adjuvant treatment, which has significantly reduced patient mortality, resistance to the endocrine treatments often develops, leading to disease recurrence and limiting clinical benefits. Emerging evidence indicates that extracellular vesicles (EVs), nanosized particles that are released by all cell types and responsible for local and systemic intercellular communications, might represent a newly identified mechanism underlying endocrine resistance. Unraveling the role of EVs, released by transformed cells during the tumor evolution under endocrine therapy, is still an open question in the cancer research area and the molecular mechanisms involved should be better defined to discover alternative therapeutic approaches to overcome resistance. In this review, we will provide an overview of recent findings on the involvement of EVs in sustaining hormonal resistance in breast cancer and discuss opportunities for their potential use as biomarkers to monitor the therapeutic response and disease progression.

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