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1.
Opioids and Sepsis: Elucidating the Role of the Microbiome and microRNA-146.
Abu, Y, Vitari, N, Yan, Y, Roy, S
International journal of molecular sciences. 2022;(3)
Abstract
Sepsis has recently been defined as life-threatening organ dysfunction caused by the dysregulated host response to an ongoing or suspected infection. To date, sepsis continues to be a leading cause of morbidity and mortality amongst hospitalized patients. Many risk factors contribute to development of sepsis, including pain-relieving drugs like opioids, which are frequently prescribed post-operatively. In light of the opioid crisis, understanding the interactions between opioid use and the development of sepsis has become extremely relevant, as opioid use is associated with increased risk of infection. Given that the intestinal tract is a major site of origin of sepsis-causing microbes, there has been an increasing focus on how alterations in the gut microbiome may predispose towards sepsis and mediate immune dysregulation. MicroRNAs, in particular, have emerged as key modulators of the inflammatory response during sepsis by tempering the immune response, thereby mediating the interaction between host and microbiome. In this review, we elucidate contributing roles of microRNA 146 in modulating sepsis pathogenesis and end with a discussion of therapeutic targeting of the gut microbiome in controlling immune dysregulation in sepsis.
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Human Breast Milk Composition and Function in Human Health: From Nutritional Components to Microbiome and MicroRNAs.
Yi, DY, Kim, SY
Nutrients. 2021;(9)
Abstract
Human breast milk (HBM) is not only an indispensable source of nutrients for early human growth and development, supplying components that support infant growth and development, but also contains various essential immunologic components with anti-infectious activities and critical roles in the formation of immunity. It is also known that HBM contains its own unique microbiome, including beneficial, commensal, and potentially probiotic bacteria, that can contribute to infant gut colonization. In addition, HBM-derived extracellular vesicles, exosomes, and microRNA are attracting increasing interest for their potential to transfer to the infant and their role in infant development. In this article, we examine some of the various constituents in HBM and review the evidence supporting their associated health effects and their potential applications in human health.
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Dietary Selenium Regulates microRNAs in Metabolic Disease: Recent Progress.
Huang, X, Dong, YL, Li, T, Xiong, W, Zhang, X, Wang, PJ, Huang, JQ
Nutrients. 2021;(5)
Abstract
Selenium (Se) is an essential element for the maintenance of a healthy physiological state. However, due to environmental and dietary factors and the narrow safety range of Se, diseases caused by Se deficiency or excess have gained considerable traction in recent years. In particular, links have been identified between low Se status, cognitive decline, immune disorders, and increased mortality, whereas excess Se increases metabolic risk. Considerable evidence has suggested microRNAs (miRNAs) regulate interactions between the environment (including the diet) and genes, and play important roles in several diseases, including cancer. MiRNAs target messenger RNAs to induce changes in proteins including selenoprotein expression, ultimately generating disease. While a plethora of data exists on the epigenetic regulation of other dietary factors, nutrient Se epigenetics and especially miRNA regulated mechanisms remain unclear. Thus, this review mainly focuses on Se metabolism, pathogenic mechanisms, and miRNAs as key regulatory factors in Se-related diseases. Finally, we attempt to clarify the regulatory mechanisms underpinning Se, miRNAs, selenoproteins, and Se-related diseases.
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The Role of miR-155 in Nutrition: Modulating Cancer-Associated Inflammation.
Zanoaga, O, Braicu, C, Chiroi, P, Andreea, N, Hajjar, NA, Mărgărit, S, Korban, SS, Berindan-Neagoe, I
Nutrients. 2021;(7)
Abstract
Nutrition plays an important role in overall human health. Although there is no direct evidence supporting the direct involvement of nutrition in curing disease, for some diseases, good nutrition contributes to disease prevention and our overall well-being, including energy level, optimum internal function, and strength of the immune system. Lately, other major, but more silent players are reported to participate in the body's response to ingested nutrients, as they are involved in different physiological and pathological processes. Furthermore, the genetic profile of an individual is highly critical in regulating these processes and their interactions. In particular, miR-155, a non-coding microRNA, is reported to be highly correlated with such nutritional processes. In fact, miR-155 is involved in the orchestration of various biological processes such as cellular signaling, immune regulation, metabolism, nutritional responses, inflammation, and carcinogenesis. Thus, this review aims to highlight those critical aspects of the influence of dietary components on gene expression, primarily on miR-155 and its role in modulating cancer-associated processes.
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5.
Non-Coding RNAs in Human Breast Milk: A Systematic Review.
Tingö, L, Ahlberg, E, Johansson, L, Pedersen, SA, Chawla, K, Sætrom, P, Cione, E, Simpson, MR
Frontiers in immunology. 2021;:725323
Abstract
UNLABELLED 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.
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6.
Central role of the placenta during viral infection: Immuno-competences and miRNA defensive responses.
Zaga-Clavellina, V, Diaz, L, Olmos-Ortiz, A, Godínez-Rubí, M, Rojas-Mayorquín, AE, Ortuño-Sahagún, D
Biochimica et biophysica acta. Molecular basis of disease. 2021;(10):166182
Abstract
Pregnancy is a unique immunological condition in which an "immune-diplomatic" dialogue between trophoblasts and maternal immune cells is established to protect the fetus from rejection, to create a privileged environment in the uterus and to simultaneously be alert to any infectious challenge. The maternal-placental-fetal interface (MPFI) performs an essential role in this immunological defense. In this review, we will address the MPFI as an active immuno-mechanical barrier that protects against viral infections. We will describe the main viral infections affecting the placenta and trophoblasts and present their structure, mechanisms of immunocompetence and defensive responses to viral infections in pregnancy. In particular, we will analyze infection routes in the placenta and trophoblasts and the maternal-fetal outcomes in both. Finally, we will focus on the cellular targets of the antiviral microRNAs from the C19MC cluster, and their effects at both the intra- and extracellular level.
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7.
MicroRNAs and exosomes: key players in HIV pathogenesis.
Sadri Nahand, J, Bokharaei-Salim, F, Karimzadeh, M, Moghoofei, M, Karampoor, S, Mirzaei, HR, Tabibzadeh, A, Jafari, A, Ghaderi, A, Asemi, Z, et al
HIV medicine. 2020;(4):246-278
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Abstract
OBJECTIVES HIV infection is well known to cause impairment of the human immune system, and until recently was a leading cause of death. It has been shown that T lymphocytes are the main targets of HIV. The virus inactivates T lymphocytes by interfering with a wide range of cellular and molecular targets, leading to suppression of the immune system. The objective of this review is to investigate to what extent microRNAs (miRNAs) are involved in HIV pathogenesis. METHODS The scientific literature (Pubmed and Google scholar) for the period 1988-2019 was searched. RESULTS Mounting evidence has revealed that miRNAs are involved in viral replication and immune response, whether by direct targeting of viral transcripts or through indirect modulation of virus-related host pathways. In addition, exosomes have been found to act as nanoscale carriers involved in HIV pathogenesis. These nanovehicles target their cargos (i.e. DNA, RNA, viral proteins and miRNAs) leading to alteration of the behaviour of recipient cells. CONCLUSIONS miRNAs and exosomes are important players in HIV pathogenesis. Additionally, there are potential diagnostic applications of miRNAs as biomarkers in HIV infection.
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8.
The role of miR-146a in viral infection.
Nahand, JS, Karimzadeh, MR, Nezamnia, M, Fatemipour, M, Khatami, A, Jamshidi, S, Moghoofei, M, Taghizadieh, M, Hajighadimi, S, Shafiee, A, et al
IUBMB life. 2020;(3):343-360
Abstract
Cellular microRNAs (miRNAs) were identified as a key player in the posttranscriptional regulation of cellular-genes regulatory pathways. They also emerged as a significant regulator of the immune response. In particular, miR-146a acts as an importance modulator of function and differentiation cells of the innate and adaptive immunity. It has been associated with disorder including cancer and viral infections. Given its significance in the regulation of key cellular processes, it is not surprising which virus infection have found ways to dysregulation of miRNAs. miR-146a has been identified in exosomes (exosomal miR-146a). After the exosomes release from donor cells, they are taken up by the recipient cell and probably the exosomal miR-146a is able to modulate the antiviral response in the recipient cell and result in making them more susceptible to virus infection. In this review, we discuss recent reports regarding miR-146a expression levels, target genes, function, and contributing role in the pathogenesis of the viral infection and provide a clue to develop the new therapeutic and preventive strategies for viral disease in the future.
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Pathogenic role of exosomes and microRNAs in HPV-mediated inflammation and cervical cancer: A review.
Sadri Nahand, J, Moghoofei, M, Salmaninejad, A, Bahmanpour, Z, Karimzadeh, M, Nasiri, M, Mirzaei, HR, Pourhanifeh, MH, Bokharaei-Salim, F, Mirzaei, H, et al
International journal of cancer. 2020;(2):305-320
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Abstract
Cervical cancer (CC) is the fourth most common cause of cancer death in women. The most important risk factor for the development of CC is cervical infection with human papilloma virus (HPV). Inflammation is a protective strategy that is triggered by the host against pathogens such as viral infections that acts rapidly to activate the innate immune response. Inflammation is beneficial if it is brief and well controlled; however, if the inflammation is excessive or it becomes of chronic duration, it can produce detrimental effects. HPV proteins are involved, both directly and indirectly, in the development of chronic inflammation, which is a causal factor in the development of CC. However, other factors may also have a potential role in stimulating chronic inflammation. MicroRNAs (miRNAs) (a class of noncoding RNAs) are strong regulators of gene expression. They have emerged as key players in several biological processes, including inflammatory pathways. Abnormal expression of miRNAs may be linked to the induction of inflammation that occurs in CC. Exosomes are a subset of extracellular vesicles shed by almost all types of cells, which can function as cargo transfer vehicles. Exosomes contain proteins and genetic material (including miRNAs) derived from their parent cells and can potentially affect recipient cells. Exosomes have recently been recognized to be involved in inflammatory processes and can also affect the immune response. In this review, we discuss the role of HPV proteins, miRNAs and exosomes in the inflammation associated with CC.
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Statin-induced microRNAome alterations modulating inflammation pathways of peripheral blood mononuclear cells in patients with hypercholesterolemia.
Lin, HJ, Yu, SL, Su, TC, Hsu, HC, Chen, MF, Lee, YT, Chien, KL, Lu, TP
Bioscience reports. 2020;(9)
Abstract
Statins inhibit cholesterol biogenesis and modulate atheroma inflammation to reduce cardiovascular risks. Promoted by immune and non-immune cells, serum C-reactive protein (CRP) might be a biomarker suboptimal to assess inflammation status. Although it has been reported that statins modulated inflammation via microRNAs (miRNAs), evidence remains lacking on comprehensive profiling of statin-induced miRNAome alterations in immune cells. We recruited 19 hypercholesterolemic patients receiving 2 mg/day pitavastatin and 15 ones receiving 10 mg/day atorvastatin treatment for 12 weeks, and performed microarray-based profiling of 1733 human mature miRNAs in peripheral blood mononuclear cells (PBMCs) before and after statin treatment. Differentially expressed miRNAs were determined if their fold changes were >1.50 or <0.67, after validated using quantitative polymerase chain reaction (qPCR). The miRSystem and miTALOS platforms were utilized for pathway analysis. Of the 34 patients aged 63.7 ± 6.2 years, 27 were male and 19 were with coronary artery disease. We discovered that statins induced differential expressions of miR-483-5p, miR-4667-5p, miR-1244, and miR-3609, with qPCR-validated fold changes of 1.74 (95% confidence interval, 1.33-2.15), 1.61 (1.25-1.98), 1.61 (1.01-2.21), and 1.68 (1.19-2.17), respectively. The fold changes of the four miRNAs were not correlated with changes of low-density-lipoprotein cholesterol or CRP, after sex, age, and statin type were adjusted. We also revealed that RhoA and transforming growth factor-β signaling pathways might be regulated by the four miRNAs. Given our findings, miRNAs might be involved in statin-induced inflammation modulation in PBMCs, providing likelihood to assess and reduce inflammation in patients with atherosclerotic cardiovascular diseases.