scholarly journals Chemoinformatic Screening for the Selection of Potential Senolytic Compounds from Natural Products

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 467
Author(s):  
Oscar Salvador Barrera-Vázquez ◽  
Juan Carlos Gómez-Verjan ◽  
Gil Alfonso Magos-Guerrero
Keyword(s):  
Natural Products ◽  
Experimental Models ◽  
Adverse Outcomes ◽  
Network Pharmacology ◽  
Chemical Databases ◽  
Network Analyses ◽  
Age Related ◽  
Potential Use ◽  
Cellular Condition ◽  
Selection Of

Cellular senescence is a cellular condition that involves significant changes in gene expression and the arrest of cell proliferation. Recently, it has been suggested in experimental models that the elimination of senescent cells with pharmacological methods delays, prevents, and improves multiple adverse outcomes related to age. In this sense, the so-called senoylitic compounds are a class of drugs that selectively eliminates senescent cells (SCs) and that could be used in order to delay such adverse outcomes. Interestingly, the first senolytic drug (navitoclax) was discovered by using chemoinformatic and network analyses. Thus, in the present study, we searched for novel senolytic compounds through the use of chemoinformatic tools (fingerprinting and network pharmacology) over different chemical databases (InflamNat and BIOFACQUIM) coming from natural products (NPs) that have proven to be quite remarkable for drug development. As a result of screening, we obtained three molecules (hinokitiol, preussomerin C, and tanshinone I) that could be considered senolytic compound candidates since they share similarities in structure with senolytic leads (tunicamycin, ginsenoside Rb1, ABT 737, rapamycin, navitoclax, timosaponin A-III, digoxin, roxithromycin, and azithromycin) and targets involved in senescence pathways with potential use in the treatment of age-related diseases.

scholarly journals BIOMARKER STRATEGIES FOR GEROSCIENCE-GUIDED CLINICAL TRIALS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S745-S746
Author(s):  
Jamie N Justice ◽  
George A Kuchel ◽  
Nir Barzilai ◽  
Stephen Kritchevsky
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Biological Aging ◽  
Expert Committee ◽  
Biomarkers Of Aging ◽  
Age Related ◽  
Trial Outcomes ◽  
Biology Of Aging ◽  
Potential Use ◽  
Selection Of

Abstract Significant progress in the biology of aging and animal models supports the geroscience hypothesis: by targeting biological aging the onset of age-related diseases can be delayed. Geroscience investigators will test this hypothesis in a multicenter clinical trial, to determine if interventions on biological aging processes can prevent accumulation of multiple age-related diseases and aging phenotypes in older adults. Prodigious activity is underway to develop markers of biological aging, but currently there is no aging biomarker consensus to support geroscience-guided clinical trial outcomes. We convened an expert committee to establish a framework for selection of blood-based biomarkers, emphasizing: feasibility/reliability; aging relevance; ability to predict clinical trial outcomes; and responsiveness to intervention. We applied this framework and identified a short-list of blood-based biomarkers with potential use in multicenter trials on aging. We review progress on efforts to test these candidate biomarkers of aging and development of biomarkers strategy for geroscience-guided clinical trials.

scholarly journals Distinct Roles of Vav Family Members in Adaptive and Innate Immune Models of Arthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 695
Author(s):  
Javier Conde ◽  
Isabel Fernández-Pisonero ◽  
Myriam Cuadrado ◽  
Antonio Abad ◽  
Javier Robles-Valero ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Family Members ◽  
Experimental Models ◽  
Innate Immune ◽  
Main Role ◽  
Zymosan A ◽  
Proliferation And Differentiation ◽  
Signal Transduction Proteins ◽  
Selection Of

Genetic evidence suggests that three members of the VAV family (VAV1, VAV2 and VAV3) of signal transduction proteins could play important roles in rheumatoid arthritis. However, it is not known currently whether the inhibition of these proteins protects against this disease and, if so, the number of family members that must be eliminated to get a therapeutic impact. To address this issue, we have used a collection of single and compound Vav family knockout mice in experimental models for antigen-dependent (methylated bovine serum albumin injections) and neutrophil-dependent (Zymosan A injections) rheumatoid arthritis in mice. We show here that the specific elimination of Vav1 is sufficient to block the development of antigen-induced arthritis. This protection is likely associated with the roles of this Vav family member in the development and selection of immature T cells within the thymus as well as in the subsequent proliferation and differentiation of effector T cells. By contrast, we have found that depletion of Vav2 reduces the number of neutrophils present in the joints of Zymosan A-treated mice. Despite this, the elimination of Vav2 does not protect against the joint degeneration triggered by this experimental model. These findings indicate that Vav1 is the most important pharmacological target within this family, although its main role is limited to the protection against antigen-induced rheumatoid arthritis. They also indicate that the three Vav family proteins do not play redundant roles in these pathobiological processes.

An enumeration of natural products from microbial, marine and terrestrial sources

2020 ◽  
Vol 5 (8) ◽  
Author(s):  
Fidele Ntie-Kang ◽  
Daniel Svozil
Keyword(s):  
Amino Acids ◽  
Natural Products ◽  
Biologically Active ◽  
Lead Compound ◽  
Chemical Databases ◽  
Natural Sources ◽  
Chemical Structures ◽  
Chemically Modified ◽  
Marine Habitats ◽  
Metabolic Properties

AbstractThe discovery of a new drug is a multidisciplinary and very costly task. One of the major steps is the identification of a lead compound, i.e. a compound with a certain degree of potency and that can be chemically modified to improve its activity, metabolic properties, and pharmacokinetics profiles. Terrestrial sources (plants and fungi), microbes and marine organisms are abundant resources for the discovery of new structurally diverse and biologically active compounds. In this chapter, an attempt has been made to quantify the numbers of known published chemical structures (available in chemical databases) from natural sources. Emphasis has been laid on the number of unique compounds, the most abundant compound classes and the distribution of compounds in terrestrial and marine habitats. It was observed, from the recent investigations, that ~500,000 known natural products (NPs) exist in the literature. About 70 % of all NPs come from plants, terpenoids being the most represented compound class (except in bacteria, where amino acids, peptides, and polyketides are the most abundant compound classes). About 2,000 NPs have been co-crystallized in PDB structures.

scholarly journals Influence of Patient Age on Streptococcus pneumoniae Serotypes Causing Invasive Disease

2001 ◽  
Vol 8 (3) ◽  
pp. 556-559 ◽  
Author(s):  
Jaime Inostroza ◽  
Ana Maria Vinet ◽  
Gloria Retamal ◽  
Pedro Lorca ◽  
Gonzalo Ossa ◽  
...  
Keyword(s):  
Age Groups ◽  
Invasive Disease ◽  
Bacterial Virulence ◽  
Host Factors ◽  
Invasive Infection ◽  
Age Group ◽  
Southern Chile ◽  
Age Related ◽  
Sterile Site ◽  
Selection Of

ABSTRACT All clinical S. pneumoniae specimens isolated from patients with invasive or sterile-site infections admitted to one regional general hospital in southern Chile were collected during a 5-year period (February 1994 to September 1999). A total of 247 strains belonging to 50 serotypes were isolated in this survey: 69 in patients under 5 years of age, 129 in patients 5 to 64 years old, and 49 from patients 65 years and older. Eight serotypes were identified in all age groups, while all other serotypes were found exclusively in one age group or in patients over 4 years of age. Serotype 3 was never found in patients under 5 years old, and serotype 14 was not found in patients >64 years of age. There was no difference in the serotypes causing infection in each one of the 5 years of the survey. Our results suggest that both bacterial virulence factors and host factors play an important role in the selection of S. pneumoniae serotypes causing invasive infection. Possible host factors include age-related differences in the immune response. Comparative studies with other areas of the world may help to further understanding of our observations in southern Chile.

scholarly journals Sonic Artefacts of Teotihuacan, Mexico (Horns, Trumpets and Pipes)

Acoustics ◽  
2021 ◽  
Vol 3 (3) ◽  
pp. 507-544
Author(s):  
Arnd Adje Both
Keyword(s):  
World Heritage ◽  
Experimental Models ◽  
Wind Instruments ◽  
Unesco World Heritage ◽  
Urban Settings ◽  
Subsequent Test ◽  
Acoustic Study ◽  
Teotihuacan Mexico ◽  
Selection Of

This paper presents the acoustic study of a sample of sonic artefacts, in particular a selection of wind instruments (horns, trumpets and pipes), from the UNESCO World Heritage Centre of Teotihuacan, Mexico, based on a thorough examination of the accessible and playable archaeological finds and the construction and subsequent test of a series of experimental models. Combined with the archaeological and iconographical information, the study helps to deduce information with regard to the urban settings in which these instruments might have been used. It also reveals some basic acoustic components of the music once performed in Teotihuacan.

Hot off the press

2021 ◽  
Vol 38 (4) ◽  
pp. 677-681
Author(s):  
Robert A. Hill ◽  
Andrew Sutherland
Keyword(s):  
Natural Products ◽  
Bioorganic Chemistry ◽  
The Press ◽  
Selection Of

A personal selection of 32 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as eurysoloid A from Eurysolen gracilis.

Advancements in capturing and mining mass spectrometry data are transforming natural products research

2021 ◽  
Author(s):  
Scott A. Jarmusch ◽  
Justin J. J. van der Hooft ◽  
Pieter C. Dorrestein ◽  
Alan K. Jarmusch
Keyword(s):  
Mass Spectrometry ◽  
Data Mining ◽  
Natural Products ◽  
Data Analysis ◽  
Community Participation ◽  
Mass Spectrometry Data ◽  
Metabolomics Data ◽  
Analysis Tools ◽  
Public Data ◽  
Potential Use

This review covers the current and potential use of mass spectrometry-based metabolomics data mining in natural products. Public data, metadata, databases and data analysis tools are critical. The value and success of data mining rely on community participation.

Anti-aging natural compounds and their role in the regulation of metabolic pathways leading to longevity

2021 ◽  
Vol 21 ◽  
Author(s):  
Aqsa Muzammil ◽  
Muhammad Waqas ◽  
Ahitsham Umar ◽  
Muhammad Sufyan ◽  
Abdur Rehman ◽  
...  
Keyword(s):  
Natural Products ◽  
Metabolic Pathways ◽  
Natural Compounds ◽  
Chronic Obstructive ◽  
Telomere Shortening ◽  
Age Related ◽  
Chronic Obstructive Pulmonary Diseases ◽  
Extended Lifespan ◽  
Ancient Times

: Aging is an unavoidable process, leads to cell senescence due to physiochemical changes in an organism. Anti-aging remedies have always been of great interest since ancient times. The purpose of anti-aging activities is to increase the life span and the quality of life. Anti-aging activities are primarily involved in the therapies of age-related disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), cardiovascular diseases, cancer and chronic obstructive pulmonary diseases. These diseases are triggered by multiple factors that are involved in numerous molecular pathways including telomere shortening, NF-κB pathway, adiponectin receptor pathway, insulin and IGF signaling pathway, AMPK, mTOR and mitochondria dysfunction. Natural products are known as effective molecules to delay the aging process through influencing metabolic pathways and thus ensure an extended lifespan. These natural compounds are being utilized in drug design and development through computational and high throughput techniques for effective pro-longevity drugs. A comprehensive study of natural compounds demonstrated with their anti-aging activities along with databases of natural products for drug designing was executed and summarized in this review article.

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