Bioactive Molecules Derived from Snake Venoms with Therapeutic Potential for the Treatment of Thrombo-Cardiovascular Disorders Associated with COVID-19

Important progress has been made on cytokine signaling in response to kidney injury in the past decade, especially cytokine signaling mediated by extracellular vesicles (EVs). For example, EVs released by injured renal tubular epithelial cells (TECs) can regulate intercellular communications and influence tissue recovery via both regulating the expression and transferring cytokines, growth factors, as well as other bioactive molecules at the site of injury. The effects of EVs on kidney tissue seem to vary depending on the sources of EVs; however, the literature data are often inconsistent. For example, in rodents EVs derived from mesenchymal stem cells (MSC-EVs) and endothelial progenitor cells (EPC-EVs) can have both beneficial and harmful effects on injured renal tissue. Caution is thus needed in the interpretation of these data as contradictory findings on EVs may not only be related to the origin of EVs, they can also be caused by the different methods used for EV isolation and the physiological and pathological states of the tissues/cells under which they were obtained. Here, we review and discuss our current understanding related to the immunomodulatory function of EVs in renal tubular repair in the hope of encouraging further investigations on mechanisms related to their antiinflammatory and reparative role to better define the therapeutic potential of EVs in renal diseases.

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Yield, Characterization, and Possible Exploitation of Cannabis Sativa L. Roots Grown under Aeroponics Cultivation

Molecules ◽

10.3390/molecules26164889 ◽

2021 ◽

Vol 26 (16) ◽

pp. 4889

Author(s):

Fabio Ferrini ◽

Daniele Fraternale ◽

Sabrina Donati Donati Zeppa ◽

Giancarlo Verardo ◽

Andrea Gorassini ◽

...

Keyword(s):

Cannabis Sativa ◽

Therapeutic Potential ◽

Total Content ◽

Bioactive Molecules ◽

Bioactive Metabolites ◽

Cultivated Plants ◽

Root Extracts ◽

Cultivation Technique ◽

Long Time ◽

Health Promoting

Cannabis sativa L. has been used for a long time to obtain food, fiber, and as a medicinal and psychoactive plant. Today, the nutraceutical potential of C. sativa is being increasingly reappraised; however, C. sativa roots remain poorly studied, despite citations in the scientific literature. In this direction, we identified and quantified the presence of valuable bioactives (namely, β-sitosterol, stigmasterol, campesterol, friedelin, and epi-friedelanol) in the root extracts of C. sativa, a finding which might pave the way to the exploitation of the therapeutic potential of all parts of the C. sativa plant. To facilitate root harvesting and processing, aeroponic (AP) and aeroponic-elicited cultures (AEP) were established and compared to soil-cultivated plants (SP). Interestingly, considerably increased plant growth—particularly of the roots—and a significant increase (up to 20-fold in the case of β-sitosterol) in the total content of the aforementioned roots’ bioactive molecules were observed in AP and AEP. In conclusion, aeroponics, an easy, standardized, contaminant-free cultivation technique, facilitates the harvesting/processing of roots along with a greater production of their secondary bioactive metabolites, which could be utilized in the formulation of health-promoting and health-care products.

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CancerGram: An Effective Classifier for Differentiating Anticancer from Antimicrobial Peptides

Pharmaceutics ◽

10.3390/pharmaceutics12111045 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1045

Author(s):

Michał Burdukiewicz ◽

Katarzyna Sidorczuk ◽

Dominik Rafacz ◽

Filip Pietluch ◽

Mateusz Bąkała ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Cancer Cells ◽

Plasma Membranes ◽

Therapeutic Potential ◽

Kappa Statistic ◽

R Package ◽

Bioactive Molecules ◽

Membrane Composition ◽

Anticancer Peptides ◽

Multicellular Organisms

Antimicrobial peptides (AMPs) constitute a diverse group of bioactive molecules that provide multicellular organisms with protection against microorganisms, and microorganisms with weaponry for competition. Some AMPs can target cancer cells; thus, they are called anticancer peptides (ACPs). Due to their small size, positive charge, hydrophobicity and amphipathicity, AMPs and ACPs interact with negatively charged components of biological membranes. AMPs preferentially permeabilize microbial membranes, but ACPs additionally target mitochondrial and plasma membranes of cancer cells. The preference towards mitochondrial membranes is explained by their membrane potential, membrane composition resulting from α-proteobacterial origin and the fact that mitochondrial targeting signals could have evolved from AMPs. Taking into account the therapeutic potential of ACPs and millions of deaths due to cancer annually, it is of vital importance to find new cationic peptides that selectively destroy cancer cells. Therefore, to reduce the costs of experimental research, we have created a robust computational tool, CancerGram, that uses n-grams and random forests for predicting ACPs. Compared to other ACP classifiers, CancerGram is the first three-class model that effectively classifies peptides into: ACPs, AMPs and non-ACPs/non-AMPs, with AU1U amounting to 0.89 and a Kappa statistic of 0.65. CancerGram is available as a web server and R package on GitHub.

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Effect of platelet-rich fibrin on cell proliferation, migration, differentiation, inflammation, and osteoclastogenesis: a systematic review of in vitro studies

Clinical Oral Investigations ◽

10.1007/s00784-019-03156-9 ◽

2019 ◽

Vol 24 (2) ◽

pp. 569-584 ◽

Cited By ~ 9

Author(s):

Franz-Josef Strauss ◽

Jila Nasirzade ◽

Zahra Kargarpoor ◽

Alexandra Stähli ◽

Reinhard Gruber

Keyword(s):

Systematic Review ◽

Cell Proliferation ◽

Wound Healing ◽

Bone Regeneration ◽

Therapeutic Potential ◽

In Vitro Studies ◽

Bioactive Molecules ◽

Platelet Rich Fibrin ◽

Regenerative Dentistry

Abstract Objective To systematically assess the effects of platelet-rich fibrin (PRF) on in vitro cellular behavior. Methods A systematic electronic search using MEDLINE database was performed. In vitro studies using PRF were considered and articles published up to June 31, 2018 were screened. Eligible studies were selected based on the use of human PRF. Results In total, 1746 titles were identified with the search terms, from these 37 met the inclusion criteria and were chosen for data extraction. In addition, 16 new studies, mainly published in 2019, were also included in the analysis resulting in 53 studies. No meta-analysis could be performed due to the heterogeneity of study designs. Included studies show that PRF enhances proliferation, migration, adhesion, and osteogenic differentiation on a variety of cell types along with cell signaling activation. Furthermore, PRF reduces inflammation, suppresses osteoclastogenesis, and increases the expression of various growth factors in mesenchymal cells. Summary and conclusions Despite some notable differences of the studies, the overall findings suggest a positive effect of PRF on cell proliferation, migration, adhesion, differentiation, and inflammation pointing towards a therapeutic potential in regenerative dentistry. Clinical relevance PRF serves as a reservoir of bioactive molecules to support wound healing and bone regeneration. Although the cellular mechanisms by which PRF supports the clinical outcomes remain unclear, in vitro research provides possible explanations. This systematic review aims to provide an update of the existing research on how PRF affects basic physiological processes in vitro. The overall findings suggest that PRF induces cell proliferation, migration, adhesion, and differentiation along with possessing anti-inflammatory properties further supporting its therapeutic potential in wound healing and bone regeneration.

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Neuroinflammation in CNS diseases: Molecular mechanisms and the therapeutic potential of plant derived bioactive molecules

PharmaNutrition ◽

10.1016/j.phanu.2020.100176 ◽

2020 ◽

Vol 11 ◽

pp. 100176 ◽

Cited By ~ 4

Author(s):

Menizibeya O. Welcome

Keyword(s):

Molecular Mechanisms ◽

Therapeutic Potential ◽

Bioactive Molecules ◽

Cns Diseases

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Therapeutic Potentials of Extracellular Vesicles for the Treatment of Diabetes and Diabetic Complications

International Journal of Molecular Sciences ◽

10.3390/ijms21145163 ◽

2020 ◽

Vol 21 (14) ◽

pp. 5163 ◽

Cited By ~ 1

Author(s):

Wei Hu ◽

Xiang Song ◽

Haibo Yu ◽

Jingyu Sun ◽

Yong Zhao

Keyword(s):

Extracellular Vesicles ◽

Diabetic Complications ◽

Therapeutic Potential ◽

Cell Communication ◽

Bioactive Molecules ◽

Future Research ◽

Cell Based Therapy ◽

Liver And Kidney ◽

Life Threatening ◽

Treatment Of Diabetes

Extracellular vesicles (EVs), including exosomes and microvesicles, are nano-to-micrometer vesicles released from nearly all cellular types. EVs comprise a mixture of bioactive molecules (e.g., mRNAs, miRNAs, lipids, and proteins) that can be transported to the targeted cells/tissues via the blood or lymph circulation. Recently, EVs have received increased attention, owing to their emerging roles in cell-to-cell communication, or as biomarkers with the therapeutic potential to replace cell-based therapy. Diabetes comprises a group of metabolic disorders characterized by hyperglycemia that cause the development of life-threatening complications. The impacts of conventional clinical treatment are generally limited and are followed by many side effects, including hypoglycemia, obesity, and damage to the liver and kidney. Recently, several studies have shown that EVs released by stem cells and immune cells can regulate gene expression in the recipient cells, thus providing a strategy to treat diabetes and its complications. In this review, we summarize the results from currently available studies, demonstrating the therapeutic potentials of EVs in diabetes and diabetic complications. Additionally, we highlight recommendations for future research.

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Dietary Flavonoids Interaction with CREB-BDNF Pathway: An Unconventional Approach for Comprehensive Management of Epilepsy

Current Neuropharmacology ◽

10.2174/1570159x17666190809165549 ◽

2019 ◽

Vol 17 (12) ◽

pp. 1158-1175 ◽

Cited By ~ 5

Author(s):

Pallavi Sharma ◽

Amit Kumar ◽

Damanpreet Singh

Keyword(s):

Therapeutic Potential ◽

Epileptic Seizures ◽

Brain Regions ◽

Camp Response Element Binding ◽

Bioactive Molecules ◽

Comorbid Conditions ◽

Beneficial Effects ◽

Comprehensive Management ◽

Dietary Flavonoids ◽

Bdnf Pathway

cAMP response element binding protein (CREB) is a key transcriptional regulator that regulates the transcription of genes related with neuronal differentiation, synaptic plasticity, learning and memory. Brain derived neurotrophic factor (BDNF), is a CREB dependent gene which plays a pivotal role in the pathogenesis of epilepsy and central comorbid conditions associated with epilepsy. However, the beneficial or detrimental consequences of CREB-BDNF activation on the induction and/or progression of seizures depend specifically on the region of brain involved and the time of activation. The bioactive molecules that alter the activity of CREB in a way to have specialized effects in different brain regions and neural circuits involved could potentially be utilized for therapeutic purposes. Flavonoids are the polyphenolic compounds which lead to phosphorylation of CREB in the hippocampus, followed by increase in extracellular signal regulated kinase (ERK) and BDNF. Several members of flavonoid family have also showed suppression of epileptic seizures via interaction with CREB/BDNF pathway. Moreover, epilepsy is often accompanied by a number of behavioural and psychological comorbid conditions that further gets aggravated by the use of conventional antiepileptic drug therapy. Multiple studies have also supported the beneficial effects of flavonoids in cognitive and memory impairments by upregulation of CREB-BDNF pathway. The current review is an attempt to collate the available preclinical and clinical studies to establish the therapeutic potential of various dietary flavonoids in comprehensive management of epilepsy with relation to CREB-BDNF pathway.

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Hitchhiking with Nature: Snake Venom Peptides to Fight Cancer and Superbugs

Toxins ◽

10.3390/toxins12040255 ◽

2020 ◽

Vol 12 (4) ◽

pp. 255 ◽

Cited By ~ 5

Author(s):

Clara Pérez-Peinado ◽

Sira Defaus ◽

David Andreu

Keyword(s):

Therapeutic Potential ◽

State Of The Art ◽

Resistant Bacteria ◽

Snake Venoms ◽

Antibiotic Resistant ◽

Anticancer Peptides ◽

Therapeutic Development ◽

Drug Leads

For decades, natural products in general and snake venoms (SV) in particular have been a rich source of bioactive compounds for drug discovery, and they remain a promising substrate for therapeutic development. Currently, a handful of SV-based drugs for diagnosis and treatment of various cardiovascular disorders and blood abnormalities are on the market. Likewise, far more SV compounds and their mimetics are under investigation today for diverse therapeutic applications, including antibiotic-resistant bacteria and cancer. In this review, we analyze the state of the art regarding SV-derived compounds with therapeutic potential, focusing on the development of antimicrobial and anticancer drugs. Specifically, information about SV peptides experimentally validated or predicted to act as antimicrobial and anticancer peptides (AMPs and ACPs, respectively) has been collected and analyzed. Their principal activities both in vitro and in vivo, structures, mechanisms of action, and attempts at sequence optimization are discussed in order to highlight their potential as drug leads.

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Natural Compounds as Regulators of the Cancer Cell Metabolism

International Journal of Cell Biology ◽

10.1155/2013/639401 ◽

2013 ◽

Vol 2013 ◽

pp. 1-16 ◽

Cited By ~ 30

Author(s):

Claudia Cerella ◽

Flavia Radogna ◽

Mario Dicato ◽

Marc Diederich

Keyword(s):

Cancer Cell ◽

Therapeutic Potential ◽

Cell Metabolism ◽

Physiological Mechanism ◽

Natural Compounds ◽

Bioactive Molecules ◽

Anticancer Activities ◽

Cancer Cell Metabolism ◽

Altered Metabolism ◽

And Migration

Even though altered metabolism is an “old” physiological mechanism, only recently its targeting became a therapeutically interesting strategy and by now it is considered an emerging hallmark of cancer. Nevertheless, a very poor number of compounds are under investigation as potential modulators of cell metabolism. Candidate agents should display selectivity of action towards cancer cells without side effects. This ideal favorable profile would perfectly overlap the requisites of new anticancer therapies and chemopreventive strategies as well. Nature represents a still largely unexplored source of bioactive molecules with a therapeutic potential. Many of these compounds have already been characterized for their multiple anticancer activities. Many of them are absorbed with the diet and therefore possess a known profile in terms of tolerability and bioavailability compared to newly synthetized chemical compounds. The discovery of important cross-talks between mediators of the most therapeutically targeted aberrancies in cancer (i.e., cell proliferation, survival, and migration) and the metabolic machinery allows to predict the possibility that many anticancer activities ascribed to a number of natural compounds may be due, in part, to their ability of modulating metabolic pathways. In this review, we attempt an overview of what is currently known about the potential of natural compounds as modulators of cancer cell metabolism.

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