THE ROLE OF SMALL RNAS IN CONTROLLING EXPRESSION OF GENES INVOLVED IN THE IMPLEMENTATION OF VIBRIO CHOLERAE PATHOGENICITY

AbstractIn plants, small RNAs have been recognized as key genetic and epigenetic regulators of development. Small RNAs are usually 20 to 30 nucleotides in length and they control, in a sequence specific manner, the transcriptional or post-transcriptional expression of genes. In this review, we present a comprehensive overview of the most recent findings about the function of small RNAs in ovule development, including megasporogenesis and megagametogenesis, both in sexual and apomictic plants. We discuss recent studies on the role of miRNAs, siRNAs and trans-acting RNAs (ta-siRNAs) in early female germline differentiation. The mechanistic complexity and unique regulatory features are reviewed, and possible directions for future research are provided.

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New trends in the pharmacological intervention of PPARs in obesity: Role of natural and synthetic compounds_

Current Medicinal Chemistry ◽

10.2174/1570162x18666201123114934 ◽

2020 ◽

Vol 28 ◽

Author(s):

Seyed Mohammad Nabavi ◽

Kasi Pandima Devi ◽

Sethuraman Sathya ◽

Ana Sanches-Silva ◽

Listos Joanna ◽

...

Keyword(s):

Tissue Expression ◽

Health Concern ◽

Pharmacological Intervention ◽

Peroxisome Proliferator ◽

Expression Of Genes ◽

Ppar Agonists ◽

Prevalence Of Obesity ◽

Peroxisome Proliferator Activated Receptors ◽

Natural And Synthetic

: Obesity is a major health concern for a growing fraction of the population, with the prevalence of obesity and its related metabolic disorders not being fully understood. Over the last decade, many attempts have been undertaken to understand the mechanisms at the basis of this condition, in which the accumulation of fat occurring in adipose tissue, leads to the pathogenesis of obesity related disorders. Among the most recent studies, those on Peroxisome Proliferator Activated Receptors (PPARs) revealed that these nuclear receptor proteins acting as transcription factors, among others, regulate the expression of genes involved in energy, lipid, and glucose metabolisms, and chronic inflammation. The three different isotypes of PPARs, with different tissue expression and ligand binding specificity, exert similar or overlapping functions directly or indirectly linked to obesity. In this study, we reviewed the available scientific reports concerning the PPARs structure and functions, especially in obesity, considering both natural and synthetic ligands and their role in the therapy of obesity and obesity-associated disorders. In the whole, the collected data show that there are both natural and synthetic compounds that show beneficial promising activity as PPAR agonists in chronic diseases related to obesity.

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The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma

Genes ◽

10.3390/genes12060902 ◽

2021 ◽

Vol 12 (6) ◽

pp. 902

Author(s):

Eva Costanzi ◽

Carolina Simioni ◽

Gabriele Varano ◽

Cinzia Brenna ◽

Ilaria Conti ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Extracellular Vesicles ◽

Tumor Metastasis ◽

Biological Processes ◽

Rna Molecules ◽

Expression Of Genes ◽

Non Coding Rna ◽

Donor Cells ◽

Relevant Role

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

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Myeloid HIF1α Is Involved in the Extent of Orthodontically Induced Tooth Movement

Biomedicines ◽

10.3390/biomedicines9070796 ◽

2021 ◽

Vol 9 (7) ◽

pp. 796

Author(s):

Christian Kirschneck ◽

Nadine Straßmair ◽

Fabian Cieplik ◽

Eva Paddenberg ◽

Jonathan Jantsch ◽

...

Keyword(s):

Bone Density ◽

Periodontal Ligament ◽

Tooth Movement ◽

Hypoxia Inducible Factor ◽

Myeloid Cells ◽

Orthodontic Tooth Movement ◽

Periodontal Ligament Fibroblasts ◽

Expression Of Genes ◽

Periodontal Bone Loss

During orthodontic tooth movement, transcription factor hypoxia-inducible factor 1α (HIF1α) is stabilised in the periodontal ligament. While HIF1α in periodontal ligament fibroblasts can be stabilised by mechanical compression, in macrophages pressure application alone is not sufficient to stabilise HIF1α. The present study was conducted to investigate the role of myeloid HIF1α during orthodontic tooth movement. Orthodontic tooth movement was performed in wildtype and Hif1αΔmyel mice lacking HIF1α expression in myeloid cells. Subsequently, µCT images were obtained to determine periodontal bone loss, extent of orthodontic tooth movement and bone density. RNA was isolated from the periodontal ligament of the control side and the orthodontically treated side, and the expression of genes involved in bone remodelling was investigated. The extent of tooth movement was increased in Hif1αΔmyel mice. This may be due to the lower bone density of the Hif1αΔmyel mice. Deletion of myeloid Hif1α was associated with increased expression of Ctsk and Acp5, while both Rankl and its decoy receptor Opg were increased. HIF1α from myeloid cells thus appears to play a regulatory role in orthodontic tooth movement.

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HbxB Is a Key Regulator for Stress Response and β-Glucan Biogenesis in Aspergillus nidulans

Microorganisms ◽

10.3390/microorganisms9010144 ◽

2021 ◽

Vol 9 (1) ◽

pp. 144

Author(s):

Sung-Hun Son ◽

Mi-Kyung Lee ◽

Ye-Eun Son ◽

Hee-Soo Park

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Aspergillus Nidulans ◽

Deletion Mutant ◽

Phenotypic Analysis ◽

Spore Viability ◽

Fungal Development ◽

Expression Of Genes ◽

Trehalose Biosynthesis

Homeobox transcription factors are conserved in eukaryotes and act as multi-functional transcription factors in filamentous fungi. Previously, it was demonstrated that HbxB governs fungal development and spore viability in Aspergillus nidulans. Here, the role of HbxB in A. nidulans was further characterized. RNA-sequencing revealed that HbxB affects the transcriptomic levels of genes associated with trehalose biosynthesis and response to thermal, oxidative, and radiation stresses in asexual spores called conidia. A phenotypic analysis found that hbxB deletion mutant conidia were more sensitive to ultraviolet stress. The loss of hbxB increased the mRNA expression of genes associated with β-glucan degradation and decreased the amount of β-glucan in conidia. In addition, hbxB deletion affected the expression of the sterigmatocystin gene cluster and the amount of sterigmatocystin. Overall, these results indicated that HbxB is a key transcription factor regulating trehalose biosynthesis, stress tolerance, β-glucan degradation, and sterigmatocystin production in A.nidulans conidia.

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Foam Cells as Therapeutic Targets in Atherosclerosis with a Focus on the Regulatory Roles of Non-Coding RNAs

International Journal of Molecular Sciences ◽

10.3390/ijms22052529 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2529

Author(s):

Amin Javadifar ◽

Sahar Rastgoo ◽

Maciej Banach ◽

Tannaz Jamialahmadi ◽

Thomas P. Johnston ◽

...

Keyword(s):

Lipid Metabolism ◽

Foam Cell ◽

Cell Formation ◽

Foam Cells ◽

Foam Cell Formation ◽

Special Focus ◽

Lipid Uptake ◽

Therapeutic Goals ◽

Expression Of Genes

Atherosclerosis is a major cause of human cardiovascular disease, which is the leading cause of mortality around the world. Various physiological and pathological processes are involved, including chronic inflammation, dysregulation of lipid metabolism, development of an environment characterized by oxidative stress and improper immune responses. Accordingly, the expansion of novel targets for the treatment of atherosclerosis is necessary. In this study, we focus on the role of foam cells in the development of atherosclerosis. The specific therapeutic goals associated with each stage in the formation of foam cells and the development of atherosclerosis will be considered. Processing and metabolism of cholesterol in the macrophage is one of the main steps in foam cell formation. Cholesterol processing involves lipid uptake, cholesterol esterification and cholesterol efflux, which ultimately leads to cholesterol equilibrium in the macrophage. Recently, many preclinical studies have appeared concerning the role of non-encoding RNAs in the formation of atherosclerotic lesions. Non-encoding RNAs, especially microRNAs, are considered regulators of lipid metabolism by affecting the expression of genes involved in the uptake (e.g., CD36 and LOX1) esterification (ACAT1) and efflux (ABCA1, ABCG1) of cholesterol. They are also able to regulate inflammatory pathways, produce cytokines and mediate foam cell apoptosis. We have reviewed important preclinical evidence of their therapeutic targeting in atherosclerosis, with a special focus on foam cell formation.

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MicroRNAs: Biological Regulators in Pathogen–Host Interactions

Cells ◽

10.3390/cells9010113 ◽

2020 ◽

Vol 9 (1) ◽

pp. 113 ◽

Cited By ~ 3

Author(s):

Stephanie Maia Acuña ◽

Lucile Maria Floeter-Winter ◽

Sandra Marcia Muxel

Keyword(s):

Immune Response ◽

Infectious Diseases ◽

Small Rnas ◽

Immune Cell ◽

Fine Tuning ◽

Biological Processes ◽

Host Interactions ◽

The Past ◽

Biological Aspects

An inflammatory response is essential for combating invading pathogens. Several effector components, as well as immune cell populations, are involved in mounting an immune response, thereby destroying pathogenic organisms such as bacteria, fungi, viruses, and parasites. In the past decade, microRNAs (miRNAs), a group of noncoding small RNAs, have emerged as functionally significant regulatory molecules with the significant capability of fine-tuning biological processes. The important role of miRNAs in inflammation and immune responses is highlighted by studies in which the regulation of miRNAs in the host was shown to be related to infectious diseases and associated with the eradication or susceptibility of the infection. Here, we review the biological aspects of microRNAs, focusing on their roles as regulators of gene expression during pathogen–host interactions and their implications in the immune response against Leishmania, Trypanosoma, Toxoplasma, and Plasmodium infectious diseases.

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Non-alcoholic fatty liver disease in mice with hepatocyte-specific deletion of mitochondrial fission factor

Diabetologia ◽

10.1007/s00125-021-05488-2 ◽

2021 ◽

Author(s):

Yukina Takeichi ◽

Takashi Miyazawa ◽

Shohei Sakamoto ◽

Yuki Hanada ◽

Lixiang Wang ◽

...

Keyword(s):

Er Stress ◽

Mitochondrial Dynamics ◽

Mitochondrial Fission ◽

Primary Hepatocytes ◽

Alcoholic Fatty Liver ◽

Expression Of Genes ◽

Specific Deletion

Abstract Aims/hypothesis Mitochondria are highly dynamic organelles continuously undergoing fission and fusion, referred to as mitochondrial dynamics, to adapt to nutritional demands. Evidence suggests that impaired mitochondrial dynamics leads to metabolic abnormalities such as non-alcoholic steatohepatitis (NASH) phenotypes. However, how mitochondrial dynamics are involved in the development of NASH is poorly understood. This study aimed to elucidate the role of mitochondrial fission factor (MFF) in the development of NASH. Methods We created mice with hepatocyte-specific deletion of MFF (MffLiKO). MffLiKO mice fed normal chow diet (NCD) or high-fat diet (HFD) were evaluated for metabolic variables and their livers were examined by histological analysis. To elucidate the mechanism of development of NASH, we examined the expression of genes related to endoplasmic reticulum (ER) stress and lipid metabolism, and the secretion of triacylglycerol (TG) using the liver and primary hepatocytes isolated from MffLiKO and control mice. Results MffLiKO mice showed aberrant mitochondrial morphologies with no obvious NASH phenotypes during NCD, while they developed full-blown NASH phenotypes in response to HFD. Expression of genes related to ER stress was markedly upregulated in the liver from MffLiKO mice. In addition, expression of genes related to hepatic TG secretion was downregulated, with reduced hepatic TG secretion in MffLiKO mice in vivo and in primary cultures of MFF-deficient hepatocytes in vitro. Furthermore, thapsigargin-induced ER stress suppressed TG secretion in primary hepatocytes isolated from control mice. Conclusions/interpretation We demonstrated that ablation of MFF in liver provoked ER stress and reduced hepatic TG secretion in vivo and in vitro. Moreover, MffLiKO mice were more susceptible to HFD-induced NASH phenotype than control mice, partly because of ER stress-induced apoptosis of hepatocytes and suppression of TG secretion from hepatocytes. This study provides evidence for the role of mitochondrial fission in the development of NASH. Graphical abstract

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Dietary starch promotes hepatic lipogenesis in barramundi (Lates calcarifer)

British Journal Of Nutrition ◽

10.1017/s0007114520001051 ◽

2020 ◽

Vol 124 (4) ◽

pp. 363-373

Author(s):

N. M. Wade ◽

L. H. Trenkner ◽

I. Viegas ◽

L. C. Tavares ◽

M. Palma ◽

...

Keyword(s):

Mammalian Target Of Rapamycin ◽

Sea Bass ◽

Metabolic Effects ◽

Lates Calcarifer ◽

Glucose Levels ◽

H Nmr ◽

Expression Of Genes ◽

Fractional Synthetic Rate ◽

Dietary Starch

AbstractBarramundi (Lates calcarifer) are a highly valued aquaculture species, and, as obligate carnivores, they have a demonstrated preference for dietary protein over lipid or starch to fuel energetic growth demands. In order to investigate how carnivorous fish regulate nutritional cues, we examined the metabolic effects of feeding two isoenergetic diets that contained different proportions of digestible protein or starch energy. Fish fed a high proportion of dietary starch energy had a higher proportion of liver SFA, but showed no change in plasma glucose levels, and few changes in the expression of genes regulating key hepatic metabolic pathways. Decreased activation of the mammalian target of rapamycin growth signalling cascade was consistent with decreased growth performance values. The fractional synthetic rate (lipogenesis), measured by TAG 2H-enrichment using 2H NMR, was significantly higher in barramundi fed with the starch diet compared with the protein diet (0·6 (se 0·1) v. 0·4 (se 0·1) % per d, respectively). Hepatic TAG-bound glycerol synthetic rates were much higher than other closely related fish such as sea bass, but were not significantly different (starch, 2·8 (se 0·3) v. protein, 3·4 (se 0·3) % per d), highlighting the role of glycerol as a metabolic intermediary and high TAG-FA cycling in barramundi. Overall, dietary starch significantly increased hepatic TAG through increased lipogenesis. Compared with other fish, barramundi possess a unique mechanism to metabolise dietary carbohydrates and this knowledge may define ways to improve performance of advanced formulated feeds.

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Distinct gene expression patterns in chronic lymphocytic leukemia defined by usage of specific VH genes

Blood ◽

10.1182/blood-2005-04-1483 ◽

2006 ◽

Vol 107 (5) ◽

pp. 2090-2093 ◽

Cited By ~ 39

Author(s):

Dirk Kienle ◽

Axel Benner ◽

Alexander Kröber ◽

Dirk Winkler ◽

Daniel Mertens ◽

...

Keyword(s):

Gene Expression ◽

Chronic Lymphocytic Leukemia ◽

Expression Patterns ◽

Gene Expression Pattern ◽

Cell Receptor ◽

Lymphocytic Leukemia ◽

Expression Of Genes ◽

Vh Genes ◽

Signaling Activation

The mutation status and usage of specific VH genes such as V3-21 and V1-69 are potentially independent pathogenic and prognostic factors in chronic lymphocytic leukemia (CLL). To investigate the role of antigenic stimulation, we analyzed the expression of genes involved in B-cell receptor (BCR) signaling/activation, cell cycle, and apoptosis control in CLL using these specific VH genes compared to VH mutated (VH-MUT) and VH unmutated (VH-UM) CLL not using these VH genes. V3-21 cases showed characteristic expression differences compared to VH-MUT (up: ZAP70 [or ZAP-70]; down: CCND2, P27) and VH-UM (down: PI3K, CCND2, P27, CDK4, BAX) involving several BCR-related genes. Similarly, there was a marked difference between VH unmutated cases using the V1-69 gene and VH-UM (up: FOS; down: BLNK, SYK, CDK4, TP53). Therefore, usage of specific VH genes appears to have a strong influence on the gene expression pattern pointing to antigen recognition and ongoing BCR stimulation as a pathogenic factor in these CLL subgroups.

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