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1.
Exploring the pathogenesis of type 2 diabetes mellitus intestinal damp-heat syndrome and the therapeutic effect of Gegen Qinlian Decoction from the perspective of exosomal miRNA.
He, L, Bao, T, Yang, Y, Wang, H, Gu, C, Chen, J, Zhai, T, He, X, Wu, M, Zhao, L, et al
Journal of ethnopharmacology. 2022;:114786
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Diabetes is a common, complex, chronic metabolic disease. A randomized, double-blind, placebo-parallel controlled clinical study has shown that Gegen Qinlian Decoction (GQD) can reduce glycosylated hemoglobin in type 2 diabetes mellitus (T2DM) intestinal damp-heat syndrome patients in a dose-dependent manner. AIM: To explore the pathogenesis of T2DM intestinal damp-heat syndrome and the therapeutic effect of GQD from the perspective of exosomal microRNA (miRNA). METHODS Eligible patients were selected and treated with GQD for 3 months to evaluate their clinical efficacy. Effective cases were matched with healthy volunteers, and saliva samples were collected. Exosomal miRNA was extracted from saliva and analyzed by chip sequencing. Subsequently, the function of the differential gene and the signal transduction pathway were analyzed using bioinformatics technology. Finally, three target miRNAs were randomly selected from the T2DM group/healthy group, and two target miRNAs in the T2DM before treatment/after treatment group were randomly selected for qPCR verification. Finally, we conducted a correlation analysis of the miRNAs and clinical indicators. The registration number for this research is ChiCTR-IOR-15006626. RESULTS (1) The expression of exosomal miRNA chips showed that there were 14 differentially expressed miRNAs in the T2DM group/healthy group, and 26 differentially expressed miRNAs in the T2DM before treatment/after treatment group. (2) Enrichment results showed that in the T2DM group/healthy group, it was primarily related to cell development, body metabolism, TGF-β, and ErbB signaling pathways. In the T2DM before treatment/after treatment group, it was mainly related to cellular metabolic regulation processes, and insulin, Wnt, and AMPK signaling pathways. (3) The qPCR verification showed that the expressions of hsa-miR-9-5p, hsa-miR-150-5p, and hsa-miR-216b-5p in the T2DM group was higher (P<0.05). Following GQD treatment, hsa-miR-342-3p and hsa-miR-221-3p were significantly downregulated (P<0.05). (4) hsa-miR-9-5p was positively correlated with BMI (P<0.05), and hsa-miR-150-5p was positively correlated with total cholesterol and triglycerides (P<0.05). The GQD efficacy-related gene hsa-miR-342-3p was positively correlated with the patient's initial blood glucose level (P<0.05), and hsa-miR-221-3p was positively correlated with total cholesterol and triglycerides (P<0.05). CONCLUSION The exosomal miRNA expression profile and signaling pathways related to T2DM intestinal damp-heat syndrome and the efficacy of GQD were established, which provides an alternative strategy for precision traditional Chinese medicine treatment.
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2.
Recent Developments in Delivery of MicroRNAs Utilizing Nanosystems for Metabolic Syndrome Therapy.
Li, T, Zhu, L, Zhu, L, Wang, P, Xu, W, Huang, J
International journal of molecular sciences. 2021;(15)
Abstract
Metabolic syndrome (MetS) is a set of complex, chronic inflammatory conditions that are characterized by central obesity and associated with an increased risk of cardiovascular diseases. In recent years, microRNAs (miRNAs) have become an important type of endocrine factors, which play crucial roles in maintaining energy balance and metabolic homeostasis. However, its unfavorable properties such as easy degradation in blood and off-target effect are still a barrier for clinical application. Nanosystem based delivery possess strong protection, high bioavailability and control release rate, which is beneficial for success of gene therapy. This review first describes the current progress and advances on miRNAs associated with MetS, then provides a summary of the therapeutic potential and targets of miRNAs in metabolic organs. Next, it discusses recent advances in the functionalized development of classic delivery systems (exosomes, liposomes and polymers), including their structures, properties, functions and applications. Furthermore, this work briefly discusses the intelligent strategies used in emerging novel delivery systems (selenium nanoparticles, DNA origami, microneedles and magnetosomes). Finally, challenges and future directions in this field are discussed provide a comprehensive overview of the future development of targeted miRNAs delivery for MetS treatment. With these contributions, it is expected to address and accelerate the development of effective NA delivery systems for the treatment of MetS.
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3.
Inter-Individual Variability in Insulin Response after Grape Pomace Supplementation in Subjects at High Cardiometabolic Risk: Role of Microbiota and miRNA.
Ramos-Romero, S, Léniz, A, Martínez-Maqueda, D, Amézqueta, S, Fernández-Quintela, A, Hereu, M, Torres, JL, Portillo, MP, Pérez-Jiménez, J
Molecular nutrition & food research. 2021;(2):e2000113
Abstract
SCOPE Dietary polyphenols have shown promising effects in mechanistic and preclinical studies on the regulation of cardiometabolic alterations. Nevertheless, clinical trials have provided contradictory results, with high inter-individual variability. This study explores the role of gut microbiota and microRNAs (miRNAs) as factors contributing to the inter-individual variability in polyphenol response. METHODS AND RESULTS 49 subjects with at least two factors of metabolic syndrome are divided between responders (n = 23) or non-responders (n = 26), depending on the variation rate in fasting insulin after grape pomace supplementation (6 weeks). The populations of selected fecal bacteria are estimated from fecal deoxyribonucleic acid (DNA) by quantitative real-time polymerase chain reaction (qPCR), while the microbial-derived short-chain fatty acids (SCFAs) are measured in fecal samples by gas chromatography. MicroRNAs are analyzed on a representative sample, followed by targeted miRNA analysis. Responder subjects show significantly lower (p < 0.05) Prevotella and Firmicutes levels, and increased (p < 0.05) miR-222 levels. CONCLUSION After evaluating the selected substrates for Prevotella and target genes of miR-222, these variations suggest that responders are those subjects exhibiting impaired glycaemic control. This study shows that fecal microbiota and miRNA expression may be related to inter-individual variability in clinical trials with polyphenols.
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4.
A Critical Review of the Therapeutic Potential of Vitamin D-Mediated Suppression of miRNA222-Associated Metabolic Defects in Polycystic Ovarian Syndrome.
Almalki, WH, Alzahrani, A, El-Daly, M, Ahmed, AF
Critical reviews in eukaryotic gene expression. 2021;(2):75-82
Abstract
Polycystic ovarian syndrome (PCOS) is a heterogeneous, persistent endocrine disease that is generally identified in 6-10% of women of reproductive age. Intriguingly, about 55-65% of patients with PCOS display insulin resistance (IR), which can be related to their body weight, ethnicity, or age. Discovering the root cause of PCOS is of particular concern due to IR and abnormal androgen secretion, and continuous attempts have been made to define the complex pathogenic network underlying the syndrome. In addition, PCOS reflects connections between various proteins, genes, and epigenetics affected by environmental influences. Genetic factors such as mutation, epigenetics, and/or expression in noncoding RNAs, particularly miRNA222, play an important role in PCOS pathophysiology and cannot be neglected. Metformin has been used traditionally as a pillar of PCOS treatment, but even effective insulin sensitization therapy can contribute to side effects that reduce patient adherence and limit treatment effectiveness. Therefore, many of the PCOS characteristics can be taken into account for the impact on hyperinsulinemic ovaries which is important in order to develop treatment strategies. Thus our primary objective is to research the therapeutic efficacy of vitamin D in the suppression of miR222 and, secondary to miR222, mediated molecular pathways involving insulin resistance and metabolic defects, which influence ovarian activity, anovula-tion, and finally infertility.
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5.
Levels of Circulating miR-122 are Associated with Weight Loss and Metabolic Syndrome.
Hess, AL, Larsen, LH, Udesen, PB, Sanz, Y, Larsen, TM, Dalgaard, LT
Obesity (Silver Spring, Md.). 2020;(3):493-501
Abstract
OBJECTIVE This study investigated whether the levels of specific serum microRNAs (miRNAs) were altered following diet-induced weight loss and whether the serum miRNAs differed in the presence of the metabolic syndrome. METHODS The study was a weight loss intervention trial with a prescribed energy deficit of approximately 500 kcal/d. Levels of 22 miRNAs were determined in serum samples from 85 participants with overweight or obesity. miRNAs were analyzed using TaqMan Array miRNA Cards and normalized to the geometric mean of spiked-in ath-miR-159a and U6 small nuclear RNA using the ΔCT method. RESULTS The average weight loss was 5.7 kg (P < 0.001). miR-122-5p (-0.18 ± 0.06 log fold relative to initial, P < 0.01) and miR-193a-5p (-0.12 ± 0.04, P < 0.01) levels decreased in response to weight loss. miR-126a-3p (0.11 ± 0.04, P = 0.01) and miR-222-3p (1.51 ± 0.12, P < 0.001) levels increased. Furthermore, a higher level of miR-122-5p was observed at baseline in participants with the metabolic syndrome compared with participants without (0.28 ± 0.08, P < 0.01). CONCLUSIONS Changes in circulating miR-122-5p, miR-126a-3p, miR-193a-5p, and miR-222-3p in response to diet-induced weight loss are demonstrated. Furthermore, assessment of miR-122-5p could be an indicator of an adverse metabolic health status independent of obesity.
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6.
Molecular aspects of pancreatic β-cell dysfunction: Oxidative stress, microRNA, and long noncoding RNA.
Saeedi Borujeni, MJ, Esfandiary, E, Baradaran, A, Valiani, A, Ghanadian, M, Codoñer-Franch, P, Basirat, R, Alonso-Iglesias, E, Mirzaei, H, Yazdani, A
Journal of cellular physiology. 2019;(6):8411-8425
Abstract
Metabolic syndrome is known as a frequent precursor of type 2 diabetes mellitus (T2D). This disease could affect 8% of the people worldwide. Given that pancreatic β-cell dysfunction and loss have central roles in the initiation and progression of the disease, the understanding of cellular and molecular pathways associated with pancreatic β-cell dysfunction can provide more information about the underlying pathways involved in T2D. Multiple lines evidence indicated that oxidative stress, microRNA, and long noncoding RNA play significant roles in various steps of diseases. Oxidative stress is one of the important factors involved in T2D pathogenesis. This could affect the function and survival of the β cell via activation or inhibition of several processes and targets, such as receptor-signal transduction, enzyme activity, gene expression, ion channel transport, and apoptosis. Besides oxidative stress, microRNAs and noncoding RNAs have emerged as epigenetic regulators that could affect pancreatic β-cell dysfunction. These molecules exert their effects via targeting a variety of cellular and molecular pathways involved in T2D pathogenesis. Here, we summarized the molecular aspects of pancreatic β-cell dysfunction. Moreover, we highlighted the roles of oxidative stress, microRNAs, and noncoding RNAs in pancreatic β-cell dysfunction.
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7.
Brazil nut intake increases circulating miR-454-3p and miR-584-5p in obese women.
Reis, BZ, Duarte, GBS, Vargas-Mendez, E, Ferreira, LRP, Barbosa, F, Cercato, C, Rogero, MM, Cozzolino, SMF
Nutrition research (New York, N.Y.). 2019;:40-52
Abstract
The Brazil nut is an excellent source of selenium (Se), an essential micronutrient for human health. In this study, we hypothesized that Brazil nut intake modulates circulating microRNAs (miRNAs) in obese women and aimed to evaluate the effects of this nut intake on circulating miRNAs in women with obesity or metabolic syndrome (MetS). A randomized controlled clinical trial was conducted on 54 subjects recruited from the Clinical Hospital in São Paulo, Brazil. Patients were randomly assigned to 2 groups: a Brazil nut group (BN group, n = 29) and a control group (CO group, n = 25); both were monitored for 2 months. BN group members were instructed to consume 1 Brazil nut (approximately 1261 μg/Se) per day; CO group members were instructed not to consume any. Biochemical parameters related to Se status and 25 circulating miRNAs in plasma were evaluated in all patients both at baseline and after 2 months. Expression levels of 2 miRNAs (miR-454-3p and miR-584-5p) were significantly increased after Brazil nut intake. To investigate the effect of MetS on circulating miRNAs at baseline, we performed comparisons between women with MetS (n = 23) and women without MetS (others, n = 31). Circulating miR-375 levels were significantly lower (P = .012) in women with MetS. In conclusion, our findings suggested that a daily intake of 1 Brazil nut increased circulating miR-454-3p and miR-584-5p expression levels in obese women, and our network analysis indicated a link between Se intake, vitamin D metabolism, and calcium homeostasis.
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8.
The Epigenetic Machinery in Vascular Dysfunction and Hypertension.
Levy, E, Spahis, S, Bigras, JL, Delvin, E, Borys, JM
Current hypertension reports. 2017;(6):52
Abstract
Hypertension (HT) is among the major components of the metabolic syndrome, i.e., obesity, dyslipidemia, and hyperglycemia/insulin resistance. It represents a significant health problem with foremost risks for chronic cardiovascular disease and a significant cause of morbidity and mortality worldwide. Therefore, it is not surprising that this disorder constitutes a serious public health concern. Although multiple studies have stressed the multifactorial nature of HT, the pathogenesis remains largely unknown. However, if we want to reduce the global prevalence of HT, restrain the number of deaths (currently 9.4 million/year in the world), and alleviate the socio-economic burden, a deeper insight into the mechanisms is urgently needed in order to define new meaningful therapeutic targets. Recently, the role of epigenetics in the development of various complex diseases has attracted much attention. In the present review, we provide a critical update on the available literature and ongoing research regarding the epigenetic modifications of genes involved in several pathways of elevated blood pressure, especially those linked to the vascular epithelium. This review also focuses on the role of microRNA (miRNA) in the regulation of gene expression associated with HT and of fetal programming mediating susceptibility to HT in adulthood.
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9.
MicroRNAs related to androgen metabolism and polycystic ovary syndrome.
Sørensen, AE, Udesen, PB, Wissing, ML, Englund, ALM, Dalgaard, LT
Chemico-biological interactions. 2016;(Pt A):8-16
Abstract
Polycystic ovary syndrome (PCOS) is a frequent endocrine disorder in women. PCOS is associated with altered features of androgen metabolism, increased insulin resistance and impaired fertility. Furthermore, PCOS, being a syndrome diagnosis, is heterogeneous and characterized by polycystic ovaries, chronic anovulation and evidence of hyperandrogenism, as well as being associated with chronic low-grade inflammation and an increased life time risk of type 2 diabetes. A number of androgen species contribute to the symptoms of increased androgen exposure seen in many, though not all, cases of PCOS Testosterone, androstenedione, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), where the quantitatively highest amount of androgen is found as DHEAS. The sulfation of DHEA to DHEAS depends on a number of enzymes, and altered sulfate metabolism may be associated with and contribute to the pathogenesis of PCOS. MicroRNAs (miRNAs) are small, non-coding RNAs that are able to regulate gene expression at the post-transcriptional level. Altered miRNA levels have been associated with diabetes, insulin resistance, inflammation and various cancers. Studies have shown that circulating miRNAs are present in whole blood, serum, plasma and the follicular fluid of PCOS patients and that these might serve as potential biomarkers and a new approach for the diagnosis of PCOS. In this review, recent work on miRNAs with respect to PCOS will be summarized. Our understanding of miRNAs, particularly in relation to PCOS, is currently at a very early stage, and additional studies will yield important insight into the molecular mechanisms behind this complex and heterogenic syndrome.
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10.
Expression of inflammation-related miRNAs in white blood cells from subjects with metabolic syndrome after 8 wk of following a Mediterranean diet-based weight loss program.
Marques-Rocha, JL, Milagro, FI, Mansego, ML, Zulet, MA, Bressan, J, Martínez, JA
Nutrition (Burbank, Los Angeles County, Calif.). 2016;(1):48-55
Abstract
OBJECTIVES The aim of this study was to evaluate the influence of a dietary strategy for weight loss (the RESMENA [reduction of metabolic syndrome in Navarra, Spain] diet) on the expression of inflammation-related microRNAS (miRNAs) and genes in white blood cells (WBC) from individuals with metabolic syndrome (MetS). METHODS The clinical, anthropometric, and biochemical characteristics of 40 individuals with MetS (20 men and 20 women; age: 48.84 ± 10.02 y; body mass index: 35.41 ± 4.42 kg/m(2)) were evaluated before and after an 8-wk hypocaloric diet based on the Mediterranean dietary pattern. Nutrient intake was assessed with a food frequency questionnaire and 48-h weighed food records. Total RNA was isolated from WBC and the expression of some inflammation-related miRNAs and mRNAs (IL-6, TNF-α, ICAM-1, IL-18, SERPINE1, VCAM-1, GAPDH) was assessed by quantitative polymerase chain reaction. RESULTS The RESMENA nutritional intervention improved most anthropometric and biochemical features. The expression of miR-155-3p was decreased in WBC, whereas Let-7b was strongly upregulated as a consequence of the dietary treatment. However, they were not correlated with the expression of the proinflammatory genes in the same cells. The changes in the expression of let-7b, miR-125b, miR-130a, miR-132-3p, and miR-422b were significantly associated with changes in diet quality when assessed by the Healthy Eating Index. Moreover, low consumption of lipids and saturated fat (g/d) were associated with higher expression of let-7b after the nutritional intervention. CONCLUSIONS The Mediterranean-based nutritional intervention was able to induce changes in the expression of let-7b and miR-155-3p in WBC from patients with MetS after 8 wk. Moreover, the quality of the diet has an important effect on the miRNAs expression changes. These results should be highlighted because these miRNAs have been associated with inflammatory gene regulation and important human diseases.