scholarly journals Seaweed and Seaweed Bioactives for Mitigation of Enteric Methane: Challenges and Opportunities

Animals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2432
Author(s):  
D. Wade Abbott ◽  
Inga Marie Aasen ◽  
Karen A. Beauchemin ◽  
Fredrik Grondahl ◽  
Robert Gruninger ◽  
...  
Keyword(s):  
Environmental Economic ◽  
Small Molecules ◽  
Health Impacts ◽  
Red Seaweed ◽  
Asparagopsis Taxiformis ◽  
Ch4 Production ◽  
Enteric Methane ◽  
Challenges And Opportunities

Seaweeds contain a myriad of nutrients and bioactives including proteins, carbohydrates and to a lesser extent lipids as well as small molecules including peptides, saponins, alkaloids and pigments. The bioactive bromoform found in the red seaweed Asparagopsis taxiformis has been identified as an agent that can reduce enteric CH4 production from livestock significantly. However, sustainable supply of this seaweed is a problem and there are some concerns over its sustainable production and potential negative environmental impacts on the ozone layer and the health impacts of bromoform. This review collates information on seaweeds and seaweed bioactives and the documented impact on CH4 emissions in vitro and in vivo as well as associated environmental, economic and health impacts.

Asparagopsis taxiformis decreases enteric methane production from sheep

2018 ◽  
Vol 58 (4) ◽  
pp. 681 ◽  
Author(s):  
Xixi Li ◽  
Hayley C. Norman ◽  
Robert D. Kinley ◽  
Michael Laurence ◽  
Matt Wilmot ◽  
...  
Keyword(s):  
Organic Matter ◽  
Methane Production ◽  
Volatile Fatty Acids ◽  
Animal Health ◽  
Long Term Effects ◽  
Asparagopsis Taxiformis ◽  
Ch4 Production ◽  
Enteric Methane ◽  
High Fibre

Asparagopsis taxiformis concentrates halogenated compounds that are known to inhibit cobamide-dependent methanogenesis in vitro and, therefore, has potential to mitigate enteric methane production. The present study investigated the effect of Asparagopsis on methane (CH4) production from sheep offered a high-fibre pelleted diet (offered at 1.2 × maintenance) at five inclusion levels of Asparagopsis for 72 days (0% (control), 0.5%, 1%, 2% and 3% organic matter basis as offered). Individual animal CH4 measurements were conducted at 21-day intervals using open-circuit respiration chambers. Asparagopsis inclusion resulted in a consistent and dose-dependent reduction in enteric CH4 production over time, with up to 80% CH4 mitigation at the 3% offered rate compared with the group fed no Asparagopsis (P < 0.05). Sheep fed Asparagopsis had a significantly lower concentration of total volatile fatty acids and acetate, but a higher propionate concentration. No changes in liveweight gain were identified. Supplementing Asparagopsis in a high-fibre diet (<2% organic matter) resulted in significant and persistent decreases in enteric methanogenesis over a 72-day period. Granulomatous and keratotic ruminal mucosa changes were identified in several sheep with Asparagopsis supplementation. While the outcomes of the present study may be extrapolated to feedlot to achieve the antimethanogenic effect associated with Asparagopsis, further work is required to define the long-term effects on productivity and animal health.

Conjugates of Classical DNA/RNA Binder with Nucleobase: Chemical, Biochemical and Biomedical Applications

2019 ◽  
Vol 26 (30) ◽  
pp. 5609-5624
Author(s):  
Dijana Saftić ◽  
Željka Ban ◽  
Josipa Matić ◽  
Lidija-Marija Tumirv ◽  
Ivo Piantanida
Keyword(s):  
Molecular Weight ◽  
Small Molecules ◽  
Biomedical Applications ◽  
Protein Targets ◽  
New Class ◽  
Rna Targets ◽  
Covalently Linked ◽  
Structural Aspects

: Among the most intensively studied classes of small molecules (molecular weight < 650) in biomedical research are small molecules that non-covalently bind to DNA/RNA, and another intensively studied class is nucleobase derivatives. Both classes have been intensively elaborated in many books and reviews. However, conjugates consisting of DNA/RNA binder covalently linked to nucleobase are much less studied and have not been reviewed in the last two decades. Therefore, this review summarized reports on the design of classical DNA/RNA binder – nucleobase conjugates, as well as data about their interactions with various DNA or RNA targets, and even in some cases protein targets are involved. According to these data, the most important structural aspects of selective or even specific recognition between small molecule and target are proposed, and where possible related biochemical and biomedical aspects were discussed. The general conclusion is that this, rather new class of molecules showed an amazing set of recognition tools for numerous DNA or RNA targets in the last two decades, as well as few intriguing in vitro and in vivo selectivities. Several lead research lines show promising advancements toward either novel, highly selective markers or bioactive, potentially druggable molecules.

Computational study for suppression of CD25/IL-2 interaction

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Moein Dehbashi ◽  
Zohreh Hojati ◽  
Majid Motovali-bashi ◽  
Mazdak Ganjalikhani-Hakemi ◽  
Akihiro Shimosaka ◽  
...  
Keyword(s):  
Small Molecules ◽  
Cancer Progression ◽  
Immune Escape ◽  
De Novo ◽  
Computational Study ◽  
Treg Cells ◽  
Homology Search ◽  
Small Interfering Rnas

AbstractCancer recurrence presents a huge challenge in cancer patient management. Immune escape is a key mechanism of cancer progression and metastatic dissemination. CD25 is expressed in regulatory T (Treg) cells including tumor-infiltrating Treg cells (TI-Tregs). These cells specially activate and reinforce immune escape mechanism of cancers. The suppression of CD25/IL-2 interaction would be useful against Treg cells activation and ultimately immune escape of cancer. Here, software, web servers and databases were used, at which in silico designed small interfering RNAs (siRNAs), de novo designed peptides and virtual screened small molecules against CD25 were introduced for the prospect of eliminating cancer immune escape and obtaining successful treatment. We obtained siRNAs with low off-target effects. Further, small molecules based on the binding homology search in ligand and receptor similarity were introduced. Finally, the critical amino acids on CD25 were targeted by a de novo designed peptide with disulfide bond. Hence we introduced computational-based antagonists to lay a foundation for further in vitro and in vivo studies.

scholarly journals Peptide-tags for site-specific protein labelling in vitro and in vivo

2016 ◽  
Vol 12 (6) ◽  
pp. 1731-1745 ◽  
Author(s):  
Jonathan Lotze ◽  
Ulrike Reinhardt ◽  
Oliver Seitz ◽  
Annette G. Beck-Sickinger
Keyword(s):  
Metal Ions ◽  
Small Molecules ◽  
Protein Localization ◽  
Specific Protein ◽  
Site Specific ◽  
Protein Labelling ◽  
Peptide Interactions ◽  
Peptide Tags

Peptide-tag based labelling can be achieved by (i) enzymes (ii) recognition of metal ions or small molecules and (iii) peptide–peptide interactions and enables site-specific protein visualization to investigate protein localization and trafficking.

scholarly journals Modelling the impact of the macroalgae Asparagopsis taxiformis on rumen microbial fermentation

2020 ◽  
Author(s):  
Rafael Muñoz-Tamayo ◽  
Juana C. Chagas ◽  
Mohammad Ramin ◽  
Sophie J. Krizsan
Keyword(s):  
Methane Production ◽  
Volatile Fatty Acids ◽  
Mean Squared Error ◽  
Microbial Fermentation ◽  
Model Structure ◽  
Red Macroalgae ◽  
Asparagopsis Taxiformis ◽  
The Impact

AbstractBackgroundThe red macroalgae Asparagopsis taxiformis is a potent natural supplement for reducing methane production from cattle. A. taxiformis contains several anti-methanogenic compounds including bromoform that inhibits directly methanogenesis. The positive and adverse effects of A. taxiformis on the rumen microbiota are dose-dependent and operate in a dynamic fashion. It is therefore key to characterize the dynamic response of the rumen microbial fermentation for identifying optimal conditions on the use of A. taxiformis as a dietary supplement for methane mitigation. Accordingly, the objective of this work was to model the effect of A. taxiformis supplementation on the rumen microbial fermentation under in vitro conditions. We adapted a published mathematical model of rumen microbial fermentation to account for A. taxiformis supplementation. We modelled the impact of A. taxiformis on the fermentation and methane production by two mechanisms, namely (i) direct inhibition of the growth rate of methanogenesis by bromoform and (ii) hydrogen control on sugars utilization and on the flux distribution towards volatile fatty acids production. We calibrated our model using a multi-experiment estimation approach that integrated experimental data with six macroalgae supplementation levels from a published in vitro study assessing the dose-response impact of A. taxiformis on rumen fermentation.Resultsour model captured satisfactorily the effect of A. taxiformis on the dynamic profile of rumen microbial fermentation for the six supplementation levels of A. taxiformis with an average determination coefficient of 0.88 and an average coefficient of variation of the root mean squared error of 15.2% for acetate, butyrate, propionate, ammonia and methane.Conclusionsour results indicated the potential of our model as prediction tool for assessing the impact of additives such as seaweeds on the rumen microbial fermentation and methane production in vitro. Additional dynamic data on hydrogen and bromoform are required to validate our model structure and look for model structure improvements. We are working on model extensions to account for in vivo conditions. We expect this model development can be useful to help the design of sustainable nutritional strategies promoting healthy rumen function and low environmental footprint.

scholarly journals A therapeutic combination of two small molecule toxin inhibitors provides pancontinental preclinical efficacy against viper snakebite

2020 ◽  
Author(s):  
Laura-Oana Albulescu ◽  
Chunfang Xie ◽  
Stuart Ainsworth ◽  
Jaffer Alsolaiss ◽  
Edouard Crittenden ◽  
...  
Keyword(s):  
Small Molecules ◽  
Enzyme Inhibitors ◽  
Interspecific Variation ◽  
Medical Emergency ◽  
Dual Inhibitor ◽  
Mortality And Morbidity ◽  
Venom Composition ◽  
Inhibitor Combination

AbstractSnakebite is a medical emergency causing high mortality and morbidity in rural tropical communities that typically experience delayed access to unaffordable therapeutics. Viperid snakes are responsible for the majority of envenomings, but extensive interspecific variation in venom composition dictates that different antivenom treatments are used in different parts of the world, resulting in clinical and fiscal snakebite management challenges. Here, we show that a number of repurposed Phase 2-approved small molecules are capable of broadly neutralizing distinct viper venom bioactivities in vitro by inhibiting different enzymatic toxin families. Furthermore, using multiple in vivo models of envenoming, we demonstrate that a single dose of a rationally-selected dual inhibitor combination consisting of marimastat and varespladib prevents lethality caused by venom from the most medically-important vipers of Africa, South Asia and Central America. Our findings strongly support the translation of combinations of safe and affordable enzyme inhibitors as novel broad-spectrum therapeutics for snakebite.

scholarly journals Regenerative Medicine and Angiogenesis; Challenges and Opportunities

2020 ◽  
Vol 10 (4) ◽  
pp. 490-501
Author(s):  
Mozhgan Jahani ◽  
Davood Rezazadeh ◽  
Parisa Mohammadi ◽  
Amir Abdolmaleki ◽  
Amir Norooznezhad ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Large Scale ◽  
Diffusion Limit ◽  
Blood Vessel Development ◽  
Engineering Technique ◽  
Challenges And Opportunities ◽  
Vessel Development ◽  
Tissue Engineering Technique

Blood vessel development is one of the most prominent steps in regenerative medicine due tothe restoration of blood flow to the ischemic tissues and providing the rapid vascularizationin clinical-sized tissue-engineered grafts. However, currently tissue engineering technique isrestricted because of the inadequate in vitro/in vivo tissue vascularization. Some challenges likeas transportation in large scale, distribution of the nutrients and poor oxygen diffusion limit theprogression of vessels in smaller than clinically relevant dimensions as well in vivo integration.In this regard, the scholars attempted to promote the vascularization process relied on the stemcells (SCs), growth factors as well as exosomes and interactions of biomaterials with all of themto enable the emergence of ideal microenvironment which is needed for treatment of unhealthyorgans or tissue regeneration and formation of new blood vessels. Thus, in the present reviewwe aim to describe these approaches, advances, obstacles and opportunities as well as theirapplication in regeneration of heart as a prominent angiogenesis-dependent organ.

Mesenchymal stem cell-derived extracellular vesicles in the failing heart: past, present, and future

2021 ◽  
Author(s):  
Catherine Karbasiafshar ◽  
Frank W. Sellke ◽  
M. Ruhul Abid
Keyword(s):  
Stem Cell ◽  
Extracellular Vesicles ◽  
Treatment Options ◽  
Current Treatment ◽  
Lifestyle Changes ◽  
Challenges And Opportunities ◽  
Artery Disease ◽  
New Treatment

Cardiovascular disease (CVD) is the leading cause of death globally. Current treatment options include lifestyle changes, medication, and surgical intervention. However, many patients are unsuitable candidates for surgeries due to comorbidities, diffuse coronary artery disease or advanced stages of heart failure. The search for new treatment options has recently transitioned from cell-based therapies to stem-cell derived extracellular vesicles (EVs). A number of challenges remain in the EV field, including the effect of comorbidities, characterization, and delivery, However, recent revolutionary developments and insight into the potential of 'personalizing' EV contents by bioengineering methods to alter specific signaling pathways in the ischemic myocardium hold promise. Here, we discuss the past limitations of cell-based therapies, and recent EV studies involving in vivo, in vitro, and omics, and future challenges and opportunities in EV-based treatments in CVD.

scholarly journals Effect of Mootral—a garlic- and citrus-extract-based feed additive—on enteric methane emissions in feedlot cattle

2019 ◽  
Vol 3 (4) ◽  
pp. 1383-1388 ◽  
Author(s):  
Breanna M Roque ◽  
Henk J Van Lingen ◽  
Hilde Vrancken ◽  
Ermias Kebreab
Keyword(s):  
Beef Cattle ◽  
Greenhouse Gas Emissions ◽  
Greenhouse Gas ◽  
Experimental Period ◽  
Feed Additive ◽  
Gas Emissions ◽  
Ch4 Emissions ◽  
Ch4 Production ◽  
Enteric Methane

Abstract: Enteric methane (CH4) production is the main source of greenhouse gas emissions from livestock globally with beef cattle contributing 5.95% of total global greenhouse gas emissions. Various mitigation strategies have been developed to reduce enteric emissions with limited success. In vitro studies have shown a reduction in CH4 emissions when using garlic and citrus extracts. However, there is paucity of data regarding in vivo studies investigating the effect of garlic and citrus extracts in cattle. The objective of this study was to quantitatively evaluate the response of Angus × Hereford cross steers consuming the feed additive Mootral, which contains extracts of both garlic and citrus, on CH4 yield (g/kg dry matter intake [DMI]). Twenty steers were randomly assigned to two treatments: control (no additive) and Mootral supplied at 15 g/d in a completely randomized design with a 2-wk covariate and a 12-wk data collection periods. Enteric CH4 emissions were measured using the GreenFeed system during the covariate period and experimental weeks 2, 6, 9, and 12. CH4 yield (g/kg DMI) by steers remained similar in both treatments for weeks 2 to 9. In week 12, there was a significant decrease in CH4 yield (23.2%) in treatment compared to control steers mainly because the steers were consuming all the pellets containing the additive. However, overall CH4 yield (g/kg DMI) during the entire experimental period was not significantly different. Carbon dioxide yield (g/kg DMI) and oxygen consumption (g/kg DMI) did not differ between treatments during the entire experimental period. DMI, average daily gain, and feed efficiency also remained similar in control and supplemented steers. The in vivo results showed that Mootral may have a potential to be used as a feed additive to reduce enteric CH4 production and yield in beef cattle but needs further investigation under various dietary regimen.

scholarly journals Targeting the Respiratory Syncytial Virus N0-P Complex with Constrained α-Helical Peptides in Cells and Mice

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Marie Galloux ◽  
Nadège Gsponer ◽  
Vanessa Gaillard ◽  
Brice Fenner ◽  
Thibaut Larcher ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Small Molecules ◽  
Mechanisms Of Action ◽  
Rsv Infection ◽  
Macrocyclic Peptides ◽  
Escape Mutants ◽  
Severe Respiratory Infection ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is the main cause of severe respiratory infection in young children worldwide, and no therapies have been approved for the treatment of RSV infection. Data from recent clinical trials of fusion or L polymerase inhibitors for the treatment of RSV-infected patients revealed the emergence of escape mutants, highlighting the need for the discovery of inhibitors with novel mechanisms of action. Here we describe stapled peptides derived from the N terminus of the phosphoprotein (P) that act as replication inhibitors. We demonstrate that these peptides inhibit RSV replication in vitro and in vivo by preventing the formation of the N0-P complex. The present strategy provides a novel means of targeting RSV replication with constrained macrocyclic peptides or small molecules and is broadly applicable to other viruses of the Mononegavirales order.

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