scholarly journals The use of nanovibration to discover specific and potent bioactive metabolites that stimulate osteogenic differentiation in mesenchymal stem cells

2020 ◽  
Author(s):  
Thomas Hodgkinson ◽  
P. Monica Tsimbouri ◽  
Virginia Llopis-Hernandez ◽  
Paul Campsie ◽  
David Scurr ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Culture Media ◽  
Biological Activities ◽  
Bioactive Metabolites ◽  
Future Research ◽  
Fludrocortisone Acetate ◽  
Therapeutic Tools ◽  
Function Relationship ◽  
Exogenous Growth Factors ◽  
Endogenous Steroid

Bioactive metabolites have wide-ranging biological activities and are a potential source of future research and therapeutic tools. Here, we use nanovibrational stimulation to induce the osteogenic differentiation of MSCs, in the absence of off-target differentiation. We show that this differentiation method, which does not rely on the addition of exogenous growth factors to the culture media, provides an artefact-free approach to identifying bioactive metabolites that specifically and potently induce osteogenesis. We first identify a highly specific metabolite as the endogenous steroid, cholesterol sulphate. Next, a screen of other small molecules with a similar steroid scaffold identified fludrocortisone acetate as being both specific and having highly potent osteogenic-inducing activity. These findings demonstrate that physical priciples can be used to identify bioactive metabolites and then metabolite potency can be optimised by examining structure-function relationship.

scholarly journals The use of nanovibration to discover specific and potent bioactive metabolites that stimulate osteogenic differentiation in mesenchymal stem cells

2021 ◽  
Vol 7 (9) ◽  
pp. eabb7921
Author(s):  
Tom Hodgkinson ◽  
P. Monica Tsimbouri ◽  
Virginia Llopis-Hernandez ◽  
Paul Campsie ◽  
David Scurr ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Culture Media ◽  
Biological Activities ◽  
Cell Stiffness ◽  
Bioactive Metabolites ◽  
Future Research ◽  
Cholesterol Sulfate ◽  
Therapeutic Tools

Bioactive metabolites have wide-ranging biological activities and are a potential source of future research and therapeutic tools. Here, we use nanovibrational stimulation to induce osteogenic differentiation of mesenchymal stem cells, in the absence of off-target, nonosteogenic differentiation. We show that this differentiation method, which does not rely on the addition of exogenous growth factors to culture media, provides an artifact-free approach to identifying bioactive metabolites that specifically and potently induce osteogenesis. We first identify a highly specific metabolite, cholesterol sulfate, an endogenous steroid. Next, a screen of other small molecules with a similar steroid scaffold identified fludrocortisone acetate with both specific and highly potent osteogenic-inducing activity. Further, we implicate cytoskeletal contractility as a measure of osteogenic potency and cell stiffness as a measure of specificity. These findings demonstrate that physical principles can be used to identify bioactive metabolites and then enable optimization of metabolite potency can be optimized by examining structure-function relationships.

scholarly journals Plant-Derived Nano and Microvesicles for Human Health and Therapeutic Potential in Nanomedicine

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 498
Author(s):  
Mariaevelina Alfieri ◽  
Antonietta Leone ◽  
Alfredo Ambrosone
Keyword(s):  
Therapeutic Potential ◽  
Biological Activities ◽  
Plant Biotechnology ◽  
Bioactive Metabolites ◽  
Anticancer Activities ◽  
Long Distance ◽  
In Vivo Models ◽  
Therapeutic Tools

Plants produce different types of nano and micro-sized vesicles. Observed for the first time in the 60s, plant nano and microvesicles (PDVs) and their biological role have been inexplicably under investigated for a long time. Proteomic and metabolomic approaches revealed that PDVs carry numerous proteins with antifungal and antimicrobial activity, as well as bioactive metabolites with high pharmaceutical interest. PDVs have also been shown to be also involved in the intercellular transfer of small non-coding RNAs such as microRNAs, suggesting fascinating mechanisms of long-distance gene regulation and horizontal transfer of regulatory RNAs and inter-kingdom communications. High loading capacity, intrinsic biological activities, biocompatibility, and easy permeabilization in cell compartments make plant-derived vesicles excellent natural or bioengineered nanotools for biomedical applications. Growing evidence indicates that PDVs may exert anti-inflammatory, anti-oxidant, and anticancer activities in different in vitro and in vivo models. In addition, clinical trials are currently in progress to test the effectiveness of plant EVs in reducing insulin resistance and in preventing side effects of chemotherapy treatments. In this review, we concisely introduce PDVs, discuss shortly their most important biological and physiological roles in plants and provide clues on the use and the bioengineering of plant nano and microvesicles to develop innovative therapeutic tools in nanomedicine, able to encompass the current drawbacks in the delivery systems in nutraceutical and pharmaceutical technology. Finally, we predict that the advent of intense research efforts on PDVs may disclose new frontiers in plant biotechnology applied to nanomedicine.

Metabolomics of Healthy Berry Fruits

2019 ◽  
Vol 25 (37) ◽  
pp. 4888-4902 ◽  
Author(s):  
Gilda D'Urso ◽  
Sonia Piacente ◽  
Cosimo Pizza ◽  
Paola Montoro
Keyword(s):  
Biological Activities ◽  
Biologically Active ◽  
In Vivo Studies ◽  
Bioactive Metabolites ◽  
Active Metabolites ◽  
Positive Effects ◽  
Cell Functions ◽  
Berry Fruits

The consumption of berry-type fruits has become very popular in recent years because of their positive effects on human health. Berries are in fact widely known for their health-promoting benefits, including prevention of chronic disease, cardiovascular disease and cancer. Berries are a rich source of bioactive metabolites, such as vitamins, minerals, and phenolic compounds, mainly anthocyanins. Numerous in vitro and in vivo studies recognized the health effects of berries and their function as bioactive modulators of various cell functions associated with oxidative stress. Plants have one of the largest metabolome databases, with over 1200 papers on plant metabolomics published only in the last decade. Mass spectrometry (MS) and NMR (Nuclear Magnetic Resonance) are the most important analytical technologies on which the emerging ''omics'' approaches are based. They may provide detection and quantization of thousands of biologically active metabolites from a tissue, working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. In the present review, we highlighted the use of MS and NMR-based strategies and Multivariate Data Analysis for the valorization of berries known for their biological activities, important as food and often used in the preparation of nutraceutical formulations.

Recent progress in marine mollusks from the South China Sea: chemical and ecological studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Song-Wei Li ◽  
Yue-Wei Guo
Keyword(s):  
South China Sea ◽  
South China ◽  
Biological Activities ◽  
The South China Sea ◽  
Bioactive Metabolites ◽  
Research Subject ◽  
Ecological Studies ◽  
The South ◽  
China Sea ◽  
Marine Mollusks

: Marine mollusks are a prolific source of secondary metabolites with complex/diverse structures and various aspects of biological activities. For above mentioned reason, these animals have been being extensively explored and became the hotspot of research subject in the recent years. It is well documented that mollusks can escape from predation by utilizing bioactive metabolites as defensive chemicals. In the last decade, the possible diet relationship between the South China Sea mollusks and their related potential prey organisms, including sponges, corals, algae, etc. have been systematically investigated. A series of interesting results have been obtained concerning the chemistry, chemoecology and pharmacological profiles of the studied marine organisms. The present review focuses on recent development dealing with chemistry, chemoecology, and bioactivity of the South China Sea mollusks and their dietary organisms.

scholarly journals Protein tyrosine phosphatase receptor type C (PTPRC or CD45)

2021 ◽  
pp. jclinpath-2020-206927
Author(s):  
Maryam Ahmed Al Barashdi ◽  
Ahlam Ali ◽  
Mary Frances McMullin ◽  
Ken Mills
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Protein Tyrosine Kinase ◽  
Biological Activities ◽  
Tyrosine Phosphatase ◽  
Cell Types ◽  
Receptor Type ◽  
Future Research ◽  
Protein Tyrosine ◽  
Type C ◽  
Almost All

The leucocyte common antigen, protein tyrosine phosphatase receptor type C (PTPRC), also known as CD45, is a transmembrane glycoprotein, expressed on almost all haematopoietic cells except for mature erythrocytes, and is an essential regulator of T and B cell antigen receptor-mediated activation. Disruption of the equilibrium between protein tyrosine kinase and phosphatase activity (from CD45 and others) can result in immunodeficiency, autoimmunity, or malignancy. CD45 is normally present on the cell surface, therefore it works upstream of a large signalling network which differs between cell types, and thus the effects of CD45 on these cells are also different. However, it is becoming clear that CD45 plays an essential role in the innate immune system and this is likely to be a key area for future research. In this review of PTPRC (CD45), its structure and biological activities as well as abnormal expression of CD45 in leukaemia and lymphoma will be discussed.

scholarly journals Unveiling Biological Activities of Marine Fungi: The Effect of Sea Salt

2021 ◽  
Vol 11 (13) ◽  
pp. 6008
Author(s):  
Micael F. M. Gonçalves ◽  
Ana Paço ◽  
Luís F. Escada ◽  
Manuela S. F. Albuquerque ◽  
Carlos A. Pinto ◽  
...  
Keyword(s):  
Marine Fungi ◽  
Culture Media ◽  
Biological Activities ◽  
Vero Cells ◽  
Growth Conditions ◽  
Sea Salt ◽  
Cytotoxic Activities ◽  
Methanolic Extracts ◽  
Assisted Extraction ◽  
Multiresistant Strains

There is an urgent need for new substances to overcome current challenges in the health sciences. Marine fungi are known producers of numerous compounds, but the manipulation of growth conditions for optimal compound production can be laborious and time-consuming. In Portugal, despite its very long coastline, there are only a few studies on marine fungi. From a collection of Portuguese marine fungi, we screened for antimicrobial, antioxidant, enzymatic, and cytotoxic activities. Mycelia aqueous extracts, obtained by high pressure-assisted extraction, and methanolic extracts of culture media showed high antioxidant, antimicrobial, and cytotoxic activities. The mycelium extracts of Cladosporium rubrum showed higher antioxidant potential compared to extracts from other fungi. Mycelia and culture media extracts of Aspergillus affinis and Penicillium lusitanum inhibited the growth of Staphylococcus aureus, Kocuria rhizophila, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, including multiresistant strains. Penicillium lusitanum and Trichoderma aestuarinum inhibited the growth of clinical strains of Candida albicans, C. glabrata, C. parapsilosis, and C. tropicalis. All extracts from culture media were cytotoxic to Vero cells. Sea salt induced alterations in the mycelium’s chemical composition, leading to different activity profiles.

scholarly journals Cellular Signal Transductions and Their Inhibitors Derived from Deep-Sea Organisms

Marine Drugs ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 205
Author(s):  
Liyan Wang ◽  
Kazuo Umezawa
Keyword(s):  
Cell Signaling ◽  
Anticancer Agents ◽  
Deep Sea ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Bioactive Metabolites ◽  
Current View ◽  
Cellular Signal ◽  
Signaling Inhibitors ◽  
Signal Transductions

Not only physiological phenomena but also pathological phenomena can now be explained by the change of signal transduction in the cells of specific tissues. Commonly used cellular signal transductions are limited. They consist of the protein–tyrosine kinase dependent or independent Ras-ERK pathway, and the PI3K-Akt, JAK-STAT, SMAD, and NF-κB-activation pathways. In addition, biodegradation systems, such as the ubiquitin–proteasome pathway and autophagy, are also important for physiological and pathological conditions. If we can control signaling for each by a low-molecular-weight agent, it would be possible to treat diseases in new ways. At present, such cell signaling inhibitors are mainly looked for in plants, soil microorganisms, and the chemical library. The screening of bioactive metabolites from deep-sea organisms should be valuable because of the high incidence of finding novel compounds. Although it is still an emerging field, there are many successful examples, with new cell signaling inhibitors. In this review, we would like to explain the current view of the cell signaling systems important in diseases, and show the inhibitors found from deep-sea organisms, with their structures and biological activities. These inhibitors are possible candidates for anti-inflammatory agents, modulators of metabolic syndromes, antimicrobial agents, and anticancer agents.

scholarly journals Effect of dexamethasone as osteogenic supplementation in in vitro osteogenic differentiation of stem cells from human exfoliated deciduous teeth

2021 ◽  
Vol 32 (1) ◽  
Author(s):  
Mariane Beatriz Sordi ◽  
Raissa Borges Curtarelli ◽  
Izabella Thaís da Silva ◽  
Gislaine Fongaro ◽  
Cesar Augusto Magalhães Benfatti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Osteogenic Differentiation ◽  
Culture Media ◽  
Deciduous Teeth ◽  
Free Calcium ◽  
Alizarin Red ◽  
Matrix Mineralization ◽  
Media Supplementation

AbstractIn in vitro culture systems, dexamethasone (DEX) has been applied with ascorbic acid (ASC) and β-glycerophosphate (βGLY) as culture media supplementation to induce osteogenic differentiation of mesenchymal stem cells. However, there are some inconsistencies regarding the role of DEX as osteogenic media supplementation. Therefore, this study verified the influence of DEX culture media supplementation on the osteogenic differentiation, especially the capacity to mineralize the extracellular matrix of stem cells from human exfoliated deciduous teeth (SHED). Five groups were established: G1—SHED + Dulbecco’s Modified Eagles’ Medium (DMEM) + fetal bovine serum (FBS); G2—SHED + DMEM + FBS + DEX; G3—SHED + DMEM + FBS + ASC + βGLY; G4—SHED + DMEM + FBS + ASC + βGLY + DEX; G5—MC3T3-E1 + α Minimal Essential Medium (MEM) + FBS + ASC + βGLY. DNA content, alkaline phosphatase (ALP) activity, free calcium quantification in the extracellular medium, and extracellular matrix mineralization quantification through staining with von Kossa, alizarin red, and tetracycline were performed on days 7 and 21. Osteogenic media supplemented with ASC and β-GLY demonstrated similar effects on SHED in the presence or absence of DEX for DNA content (day 21) and capacity to mineralize the extracellular matrix according to alizarin red and tetracycline quantifications (day 21). In addition, the presence of DEX in the osteogenic medium promoted less ALP activity (day 7) and extracellular matrix mineralization according to the von Kossa assay (day 21), and more free calcium quantification at extracellular medium (day 21). In summary, the presence of DEX in the osteogenic media supplementation did not interfere with SHED commitment into mineral matrix depositor cells. We suggest that DEX may be omitted from culture media supplementation for SHED osteogenic differentiation in vitro studies.

Chemical Constituents and Biological Activities of Cordia Myxa L.: A Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Varinder Singh ◽  
Ankita Sood ◽  
Simran Pruthi ◽  
Manjinder Singh ◽  
Balraj Saini ◽  
...  
Keyword(s):  
Biological Activities ◽  
Chemical Constituents ◽  
Antimicrobial Activities ◽  
Functional Health ◽  
Future Research ◽  
Health Food ◽  
Toxicological Evaluation ◽  
Cordia Myxa ◽  
Chronic Fever ◽  
Tract Infections

Background: Cordia myxa L. (CM) is a valuable ethnomedicinal plant from Boraginaceae family. Traditionally, CM parts especially fruits and leaves are used in chest and urinary tract infections, diarrhoea, dysentery, tuberculosis, liver and spleen disorders, chronic fever, malaria etc. Objective: Despite of known importance and uses, CM has gained relatively less attention of researchers and concise reviews revealing the medicinal potential of CM are scanty. The present review summarizes the chemical constituents and biological activities of CM and aims to stimulate future research to develop it as a functional health food. Results: Analysis of literature on CM showed that its fruits are a rich source of nutrients and are frequently employed in wide ailments such as urinary and respiratory tract infections, chronic fever, liver disorders, asthma, used as anthelmintic, diuretic, expectorant and purgative. Scientific studies have shown the antidiabetic, analgesic, anti-inflammatory, anti-cancer, antioxidant, antiplasmodial, hepatoprotective, hypotensive, antiulcer and antimicrobial activities of CM. More than 45 compounds belonging to carbohydrates, steroids, carotenoids, phenols, flavonoids and alkaloids have been reported from various parts of CM. Conclusion: Systematic preclinical studies support the traditional claims of CM. The analysis of available literature showed that CM could be developed as a drug. Further, studies such as detailed pharmacological and toxicological evaluation, isolation of bioactive compounds, quantitative phytochemistry and structure activity relationship are scanty and thus, crucial to be addressed for uplifting the scientific value of this revered medicinal plant.

Dreams and Death: An Exploration of the Literature

1990 ◽  
Vol 21 (4) ◽  
pp. 259-281 ◽  
Author(s):  
Kelly Cookson
Keyword(s):  
Fear Of Death ◽  
Future Research ◽  
Human Response ◽  
Therapeutic Tools

The literature on dreams and death is reviewed along three lines of interest: dreams as they relate to fear of death, dreams as they relate to bereavement, and dreams as they relate to dying. It is suggested that dreams can broaden our understanding of the human response to death and provide therapeutic tools when that response becomes complicated. Theoretical implications and possible areas of future research are also discussed.

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