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Objectives: Nearly three years into the pandemic, SARS-CoV-2 infections are occurring in vaccinated and naturally infected populations. While humoral and cellular responses in COVID-19 are being characterized, novel immune biomarkers also being identified. Recently, an increase in angiotensin-converting enzyme 2 expressing (aka, ACE2 positive) circulating exosomes (ExoACE2) were identified in the plasma of COVID-19 patients (El-Shennawy et al.). In this pilot study, we describe a method to characterize the exosome-associated microRNA (exo-miRNA) signature in ACE2-positive and ACE2-negative exosomal populations (non-ExoACE2)., Methods: We performed a sorting protocol using the recombinant biotin-conjugated SARS CoV-2 spike protein containing the receptor binding domain (RBD) on plasma samples from six patients. Following purification, exo-miRNA were characterized for ACE2-positive and ACE2-negative exosome subpopulations by RT-PCR., Results: We identified differential expression of several miRNA. Specifically let-7g-5p and hsa-miR-4454+miR-7975 were upregulated, while hsa-miR-208a-3p and has-miR-323-3p were downregulated in ExoACE2 vs. non-ExoACE2., Conclusions: The SARS CoV-2 spike-protein guided exosome isolation permits isolation of ExoACE2 exosomes. Such purification facilitates detailed characterization of potential biomarkers (e.g. exo-miRNA) for COVID-19 patients. This method could be used for future studies to further the understanding mechanisms of host response against SARS CoV-2., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Breast milk is an essential source of nutrition and hydration for the infant. In addition, this highly complex biological fluid contains numerous immunologically active factors such as microorganisms, immunoglobulins, cytokines and microRNAs (miRNAs). Here, we set out to predict the function of the top 10 expressed miRNAs in human breast milk, focusing on their relevance in oral tolerance development and allergy prevention in the infant. The top expressed miRNAs in human breast milk were identified on basis of previous peer-reviewed studies gathered from a recent systematic review and an updated literature search. The miRNAs with the highest expression levels in each study were used to identify the 10 most common miRNAs or miRNA families across studies and these were selected for subsequent target prediction. The predictions were performed using TargetScan in combination with the Database for Annotation, Visualization and Integrated Discovery. The ten top expressed miRNAs were: let-7-5p family, miR-148a-3p, miR-30-5p family, miR-200a-3p + miR-141-3p, miR-22-3p, miR-181-5p family, miR-146b-5p, miR-378a-3p, miR-29-3p family, miR-200b/c-3p and miR-429-3p. The target prediction identified 3,588 potential target genes and 127 Kyoto Encyclopedia of Genes and Genomes pathways; several connected to the immune system, including TGF-b and T cell receptor signaling and T-helper cell differentiation. This review highlights the role of breast milk miRNAs and their potential contribution to infant immune maturation. Indeed, breast milk miRNAs seem to be involved in several pathways that influence oral tolerance development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ahlberg, Al-Kaabawi, Thune, Simpson, Pedersen, Cione, Jenmalm and Tingö.)

Plants possess an arsenal of different classes of small RNAs (sRNAs) of variable size, which play a regulatory role in a multitude of physiological and pathological processes via transcriptional or post-transcriptional gene silencing. The hard challenges that agriculture will face in the next few decades, such as an increasing demand for agrifood production related to the global increase in population, have stimulated the development of innovative biotechnological approaches in agriculture. In this regard, the use of artificial sRNAs has already been exploited successfully for many purposes, including control of severe plant diseases, improvement of genetic and agronomic traits of cultivated species, and increasing the nutritional value of plant foodstuffs. This strategy relies on the application of synthetic sRNA molecules to induce specific physiological responses by triggering appropriate RNA silencing pathways. This review contextualizes the use of artificial sRNAs in consideration of the huge diversity of RNA silencing mechanisms in plants. Additionally, the discussion also examines microRNAs from edible plants and exosome-like vesicles, also known as plant-derived edible nanoparticles (ENPs), which themselves can act as micronutrients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

It is now well established that lifestyle, particularly eating habits, modulates the synthesis and action of microRNAs (miRNAs). In particular, several nutritional schemes have proven effective in improving body composition, but molecular mechanisms still need to be fully understood. Within the complex physiological network of food intake regulation, it is essential to understand the changes in endocrine activity after the reduction of adipose tissue during a weight loss program. This could be the key to identifying the optimal endocrine profile in high responders, the assessment of musculoskeletal status, and long-term management. In this review, we summarize the state of the art regarding miRNAs as a function of weight loss and as a mechanistic regulator of the effectiveness of the nutritional program., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 20 to 25 nucleotides, present in all body fluids; they can be used as biomarkers, but much more than this as a therapy to replace missing protein or to downregulate excess or aberrant synthesis; here we report possible insight to future studies, needed in this exciting field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Breast milk is the primary source of nutrition and hydration for the newborn infant but also plays an important role in the child's first immune defense. Additionally, several breast milk factors have been implicated in immune-related health outcomes later in life, including immunoglobulins, cytokines, chemokines, growth factors and, more recently, non-coding RNA (ncRNA) species. In this systematic review, we provide a comprehensive summary of the current literature on endogenous ncRNAs found in human breast milk. Thirty (30) relevant studies were identified and, whilst the majority studies focused on microRNAs (miRNAs), there is evidence that breast milk contains high quantities of RNA which also include long-coding RNAs, circular RNAs, as well as other short RNAs and fragmented tRNA and rRNAs. Among studies investigating miRNAs, miR-148a-3p, miR-30a/d-5p, miR-22-3p, miR-146b-5p, miR-200a/c-3p, and the 5p end of the let-7 miRNAs were commonly reported among the top 10 miRNAs in the cell, lipid, and skim milk fractions of breast milk. Methodological difference and small sample sizes limit the possibility of conclusively identifying which maternal and infant characteristics affect the miRNA profile. The highly expressed miRNAs were generally reported to be similar across lactational stage, milk fraction, maternal and infant characteristics, or infant growth and health. All the same, individual studies identify potential differences in miRNA expression levels which should be confirmed by future studies. Stability, uptake, and physiological functions of miRNAs were also considered in several studies. Breast milk miRNAs are relatively resistant to a range of harsh conditions and uptake experiments suggest that extracellular vesicles containing miRNAs and circular RNAs can be taken up by intestinal epithelial cells. Although the evidence regarding the functional effect of breast milk miRNAs is limited, the predicted functions range from metabolic and biosynthetic processes to signaling pathways, cellular adhesion, communication, growth, and differentiation. Finally, this systematic review highlights some of the methodological challenges and knowledge gaps which can help direct future research in this field. In particular, it is important to further investigate the bioavailability of miRNAs in different milk fractions, and to characterize other ncRNAs which are largely unstudied., Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=138989, identifier CRD42020138989., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tingö, Ahlberg, Johansson, Pedersen, Chawla, Sætrom, Cione and Simpson.)

Sarcopenia and malnutrition are commonly occurring conditions in the elderly that frequently coexist, leading to substantial effects on morbidity/mortality. Evidence established muscle-specific microRNAs (miRNAs) or myomiRs as essential regulators of skeletal muscle processes, from myogenesis to muscle homeostasis. This study aimed to evaluate the association between myomiRs and sarcopenia and explore the potential of nutrition in mediating this association. qPCR was employed to characterize the myomiR-1, -133a/b, -206, -208b, and -499 expression profiles of 109 non-sarcopenic and 109 sarcopenic subjects. In our sample, the proportion malnourished or at-risk subjects was higher in sarcopenia ( p < 0.001). Among the detected myomiRs (miR-133a/b and miR-206), lower levels of miR-133b was significantly associated with the presence of sarcopenia ( p = 0.006); however, this relationship was not independent from nutritional status in multivariate analysis, suggesting a mediating effect of nutrition on the relationship between miR-133b and sarcopenia. Correlation analyses showed that lower miR-133b levels were associated with poor nutritional status (Mini Nutritional Assessment Long Form (MNA-LF) score, p = 0.005); furthermore, correlations with albumin, ferritin, and iron were found. Similar results were obtained for miR-206. Statistically more significant correlations were observed in subjects with sarcopenia. In conclusion, our findings highlight a nutrient-miR-133b/miR-206 pathway having a potential role in the age-related muscle decline., Competing Interests: The authors declare no conflict of interest.

Background: The Ketogenic Diet (KD) promotes metabolic changes and optimizes energy metabolism. It is unknown if microRNAs (miRs) are influenced by KD in obese subjects. The screening of circulating miRs was performed with the FDA approved platform n-counter flex and blood biochemical parameters were dosed by ADVIA 1800., Objectives: The aim of this study was to evaluate mir profile under 6 weeks of biphasic KD in obese subjects. We enrolled 36 obese subjects (18 females and 18 males) in stage 1 of Edmonton Obesity Staging System (EOSS) parameter., Result: Any correlation was found between biochemical parameter and three miRs, hsa-let-7b-5p, hsa-miR-143-3p and hsa-miR-504-5p influenced in an equal manner in both sexes. The KD resulted safe and ameliorate both biochemical and anthropometric factors in obese subjects re-collocating them into stage 0 of EOSS parameters., Conclusion: The miRs herein identified under KD might be a useful tool to monitor low carbohydrate nutritional regimens which reflect indirectly the regulatory biochemical mechanisms and cell signaling that orchestrate metabolic and signaling pathways., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Human Milk (HM) is a biological fluid representing the first nutrient for newborns. It directly impacts the development of the infant's immune system. In this concern, specific microRNAs (miRNAs) such as hsa-miR-21, hsa-miR-181a, hsa-miR-150 and hsa-miR-223 are known to be involved in the innate and acquired immune response., Objective: Herein, these miRNAs were evaluated in frozen and pasteurized samples of human colostrum and HM in order to elucidate the distribution and the expression profile of these biological mediators in both biological fluids., Methods: Using quantitative approach qRT-PCR, we analyzed immune-related microRNAs in both, colostrum and HM., Results: Our study provided evidence of a comparable profile of immune specific miRNAs in colostrum and HM. Although we detected all the four miRNAs tested, we point out the prevalence of hsamiR- 181a and hsa-miR-223 indicative to act on T and granulocytes cell populations as selective targets. Therefore, these biomolecules could affect newborn's immune homeostasis at early stages of life. While, variation in immune-related miRNAs was found in HM amongst lactating women, it was not evidenced in colostrum. Of interest, pasteurization procedure did not alter the distribution or the expression profile of the miRNAs tested in both colostrum and HM. Herein, we also proposed a simple method to determine the quantity of these biomolecules in biological fluids., Conclusion: Considering, this evidence the variation in immune-related miRNAs should be take into account and could be relevant for preterm and hospitalized infants who usually received pasteurized HM from donors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Migraine is a prevalent neurovascular disorders with a complex pathophysiology and therapeutic options characterized by important side effects or problems related to drug abuse. No specific biomarkers are recognized to be univocal for this subclinical condition, yet. In this concern microRNAs (miRNAs) have been suggested as potentially useful screening/diagnostic tool, and research is underway to recognize the most effective candidate(s). In this concern in the present review we Herein we highlighted miRs involvement in pain and migraine, as well as drug response and efficacy focusing also on miRs panel results from mice model with multiple induced pain conditions, and human patients with migraine in order to understand if there are similar miRs expression pattern may useful into human translational studies., Results: During human migraine attack specific miRs were found dysregulated, as well as in mouse models with different pain conditions. Amongst all the miRs screened in mice/human suffering of pain the miR-590-5p was found alterated. This latter miR, in mice is modulated by celecoxib, while in human is dysregulated in the complex regional pain syndrome, condition where migraine assume a risk factor for its development. Recently has been reported that pharmacological treatments, indirectly can pertubate miRNA expression results. Therefore, miR-590-5p could assume an interesting double meaning for a clinical point of view. It can be considered biomarker of general pain, including migraine and also biomarker to evaluate the efficacy of the drug treatment. This could be of great importance in infant-juvenile segment, where the diagnosis of migraine is very challenging. In this view, since therapy is often started with NSAIDs herein we discuss also how the discovery of the new role of miRNAs in determining drug efficacy open a new scenario in the pain-migraine tailored therapy and pharmacogenomics concept., Conclusion: miRNAs could have a pleiotropic meaning in the clinical management of migraine and could represent biomarkers of pathology, of drug efficacy as well as drug adherence to the treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Functional studies indicate that essential cellular processes are controlled by Vitamin A derivatives. Among these the retinoic acid isoforms, all-trans- and 9-cis (9cRA), regulate the expression of various genes in both physiological and pathological conditions. Using several in vitro experimental models such as pancreatic β-cells, pre-adipocytes and breast cancer cells with different phenotypes, we demonstrated the capability of 9cRA to modulate myotrophin (Mtpn) and miR-375 expressions. The 9cRA effect in pancreatic β-cells line INS-1 832/13 point out a decreased expression of Mptn at both mRNA and protein levels associated to a concomitant increase of miR-375. We also studied the effect of this molecule on 3T3-L1 pre-adipocytes cells demonstrating a down-regulation of Mtpn and a dramatic increase of miR-375. Moreover, in the in vitro breast cancer model such as MDA-MB-231 and MCF-7 cells, 9cRA showed different effect on both Mtpn and miR-375 expression. In INS-1 832/13, 3T3-L1 pre-adipocytes and MCF-7 but not in MDA-MB-231, the effect of 9cRA on Mptn gene expression and its miR was under the control of RARs and RXRs receptors, as revealed by the exposure of these cell line to LE540 or HX603 receptor antagonists. In our findings 9cRA emerges has a hormone with a regulatory action on miR-375 that in most cases interfere with Mtpn expression., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Among the clinical spectrum of neurological diseases, migraine is often associated with cerebro-vasculopathy. Impairment of neuroimmune mediators in the central nervous system has been recognized in the pathophysiology of migraine-related stroke. Although genetic correlation was found in patients with migraine-related stroke, the epidemiology of this disease indicates a need in biomarker searching discovery and validation. In this view, small molecule, called microRNAs (miRNAs), able to regulate immune and neuronal processes has been reported in patients with migraine and ischemic stroke and unambiguous miRNAs related to these diseases could be established as new molecular indicator of precocity for clinical and/or pharmacological intervention. Therefore, further exploration of this area is necessary, as greater understanding of these biomarkers could reveal the common mechanisms involved in the pathophysiology of migraine in patients with cerebral infarct., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)