Macronutrient modulation of mRNA and microRNA function in animals: A review

Dietary macronutrients have been regarded as a basic source of energy and amino acids that are necessary for the maintenance of cellular homeostasis, metabolic programming as well as protein synthesis. Due to the emergence of "nutrigenomics", a unique discipline that combines nutritional and omics technologies to study the impacts of nutrition on genomics, it is increasingly evident that macronutrients also have a significant role in the gene expression regulation. Gene expression is a complex phenomenon controlled by several signaling pathways and could be influenced by a wide variety of environmental and physiological factors. Dietary macronutrients are the most important environmental factor influencing the expression of both genes and microRNAs (miRNA). miRNA are tiny molecules of 18 to 22 nucleotides long that regulate the expression of genes. Therefore, dietary macronutrients can influence the expression of genes in both direct and indirect manners. Recent advancements in the state-of-the-art technologies regarding molecular genetics, such as next-generation sequencing, quantitative PCR array, and microarray, allowed us to investigate the occurrence of genome-wide changes in the expression of genes in relation to augmented or reduced dietary macronutrient intake. The purpose of this review is to accumulate the current knowledge focusing on macronutrient mediated changes in the gene function. This review will discuss the impact of altered dietary carbohydrate, protein, and fat intake on the expression of coding genes and their functions. In addition, it will also summarize the regulation of miRNA, both cellular and extracellular miRNA, expression modulated by dietary macronutrients. (C) 2020, Chinese Association of Animal Science and Veterinary Medicine. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd

Relative abundance of extra-cellular miRNAs in bovine follicular fluid: Implication for cell–cell communication during oocyte growth

Here we aimed to investigate the expression patternof the circulating extra-cellular miRNAs in exosome andnon-exosomal fraction of follicular fluid consisted of fullygrown or growing oocytes and to validate exosome medi-ated Here we aimed to investigate the expression patternof the circulating extra-cellular miRNAs in exosome andnon-exosomal fraction of follicular fluid consisted of fullygrHere we aimed to investigate the expression patternof the circulating extra-cellular miRNAs in exosome andnon-exosomal fraction of follicular fluid consisted of fullygrown or growing oocytes and to validate exosome medi-ated cell–cell communication between follicular cells. Forthis, follicles of 5–8mm diameter (n=120) were isolatedand individual COCs were subjected to brilliant cresyl blue(BCB) staining and classified as BCB+ (fully grown,n=60)and BCB−(growing,n=60) groups. The correspondingfollicular fluid, granulosa cells and theca cells were usedfor further molecular analysis. miRNAs isolated fromexosomal and nonexosomal portion of follicular fluidfrom the two categories was used for cDNA synthesis andsubsequent analysis using a human miRNA PCR array (with745 miRNA).own or growing oocytes and to validate exosome medi-ated cell–cell communication between follicular cells. Forthis, follicles of 5–8mm diameter (n=120) were isolatedand individual COCs were subjected to brilliant cresyl blue(BCB) staining and classified as BCB+ (fully grown,n=60)and BCB−(growing,n=60) groups. The correspondingfollicular fluid, granulosa cells and theca cells were usedfor further molecular analysis. miRNAs isolated fromexosomal and nonexosomal portion of follicular fluidfrom the two categories was used for cDNA synthesis andsubsequent analysis using a human miRNA PCR array (with745 miRNA).cell–cell communication between follicular cells. Forthis, follicles of 5–8mm diameter (n=120) were isolatedand individual COCs were subjected to brilliant cresyl blue(BCB) staining and classified as BCB+ (fully grown,n=60)and BCB−(growing,n=60) groups. The correspondingfollicular fluid, granulosa cells and theca cells were usedfor further molecular analysis. miRNAs isolated fromexosomal and nonexosomal portion of follicular fluidfrom the two categories was used for cDNA synthesis andsubsequent analysis using a human miRNA PCR array (with745 miRNA).</p

The Expression of IL-1β gene In Response to Mannheimia haemolytica Bacteria in Sheep Alveolar Macrophages in vitro

Small ruminants, particularly sheep, are suffering from many respiratory diseases.Among the causative agents of respiratory diseases, the most important microorganismsare Mannheimia haemolytica. In the case of a most severe form of infection which iscommonly known as the severe fibrinous pleuropneumonia characterized by fibrindeposition and merging, intra-alveolar hemorrhage, forceful leukocyte infiltration inalveoli of the lungs. Being a Gram-negative bacterium, Mannheimia haemolytica iscausing respiratory diseases in animals and pneumonia which is the must dangersdiseases that make a great economic loss. The sheep immune system is responsible forthe detection, capturing and elimination of foreign bodies including bacteria. However,there are no substantial studies explaining the molecular mechanism of respiratorydiseases and immune system response in sheep lung. Therefore, this study wasconducted to investigate the expression pattern of IL-1β, one of the important genes inimmune system, to understand the molecular mechanism underlying in M. haemolyticainduced infection in sheep lung.&nbsp;</p

Intracellular drug delivery by exosomes: Present condition and future perspectives

Nanotechnology plays a crucial part in the detection, diagnosis, andtreatment of a wide variety of human diseases including cancer. The recentdecades have witnessed a rapid development of nanocarriers as drug deliverysystem. Using nanocarriers have several pharmacokinetics and safety profiles inaddition to the increased bioavailability of the entrapped molecules. However,there are several obstacles in attaining the goal of successful clinicaltranslation of nanocarrier-based drug delivery system because of the safety,stability and delivery efficiency of nanocarriers. In this scenario, exosomecould be an excellent alternative to conventional drug delivery agents. Exosomesare bi-layered nanovesicles of 40-100 nm diameter and contain differentbioactive molecules including microRNAs, mRNAs, DNA fragments, and proteins.Exosomes are actively released by healthy cells in the extracellular matrix andcan be taken up by the surrounding or distant cells. Due to their inherentability to carry bioactive molecules, exosomes emerged as a versatile drugvehicle and have attracted the attention of many researchers. The most impressivecharacteristics of exosomes are nanosized, non-immunogenic due to similarcomposition as body’s own cells, high biocompatibility, readily bioavailable,ability to penetrate biological barriers, and encapsulation of various cargowhich significantly distinguish them from other conventional nanocarriers. Itis important to note that recently exosome-based nanocarriers containing smalldrug molecules and bioactive macromolecules have been developed for thetreatment of several prevalent diseases such as cancer, central nervous systemdisorders, and other degenerative diseases. Nanocarriers based on exosomes haveenormous prospects in overcoming several difficulties faced in gene and drugdelivery. This article will briefly highlight the advancement as well as thechallenges of exosome-based nanocarriers as drug delivery system. In addition,it will also discuss the future perspectives of exosome-based drug deliverysystem. Special attention will be placed on the exosomal biogenesis, releasemechanisms, and advantages of using exosomes containing special cargo, as adrug delivery system, in treating obstinate diseases. The aim is to offer newinsights for exploring exosomes in the emerging field of drug delivery.&nbsp;</p

Extracellular/Circulating MicroRNAs: Release Mechanisms,Functions and Challenges

AbstractMicroRNAs (miRNAs) are endogenously initiated, small non-coding RNAs and typically regulate the expression of mRNAs in post transcriptional level either via translational repression or mRNA degradation. Aberrant expression of miRNAs is observed in diverse disease and altered physiological states. Recently, it has been revealed that miRNAs are not only present in cells but also in extracellular milieu especially in different bio-fluids including blood plasma, follicular fluid and even in cell culture media. Such extracellular miRNAs (ECmiRNAs) are remarkably stable in the extracellular harsh environment with the presence of high RNAse activity. Although the precise mechanisms of release of cellular miRNAs to extracellular environment remain largely unknown, recent studies suggest that the expression of these ECmiRNAs can be associated with patho-physiological condition of an organism. Moreover, these ECmiRNAs may deliver to the recipient cells via certain pathways where they can regulate translational activity of target genes. This review will discuss the nature and stability of ECmiRNAs along with their release mechanisms. Furthermore, based on recent evidences, it also summarizes the possible function of these ECmiRNAs in distant cell-to-cell communication and the difficulties we may face during ECmiRNA research

Choice of samples in extracellular microRNA research: Which fraction is better- exosomal or nonexosomal?

MicroRNAs (miRNAs) are a species of noncoding RNA that post-transcriptionally regulates the expression of target mRNAs via degradation or translational repression. Recently, miRNAs in biofluids got extraordinary research priority in the field of noninvasive biomarker development because of their association with pathophysiological events, noninvasive way to obtain, and are markable stability in the extracellular harsh environment. Although several hypotheses have been proposed, the precise mechanisms of cellular release of extracellular miRNAs are not properly understood. In addition, it is often confusing to the researchers, which fraction of biofluid (based on release mechanisms) is suitable for biomarker development research. This review will briefly introduce extracellular miRNAs (EC miRNAs) and their release mechanisms. Furthermore, based on recent evidence, it will also summarize and suggest the appropriate fraction of biofluid to work with for biomarker development.</p