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1.
Critical aspects of the physiological interactions between lead and magnesium.
Wyparło-Wszelaki, M, Machoń-Grecka, A, Wąsik, M, Dobrakowski, M
Journal of biochemical and molecular toxicology. 2022;(2):e22964
Abstract
Despite technological progress, exposure to lead is an ongoing problem. There are many mechanisms governing the toxic effects of lead on the human body. One such mechanism involves the interaction of this xenobiotic with bivalent metal ions, including magnesium. Literature data suggest that the competition between these elements for binding sites at the molecular and cellular levels, as well as at the systemic level, may represent an important aspect of lead toxicity in the human body. This is especially clear in the context of oxidative stress, immune response, and gene expression modifications. This review aims to summarize current knowledge regarding these issues.
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2.
Phytochemicals as Potential Epidrugs in Type 2 Diabetes Mellitus.
Ramírez-Alarcón, K, Victoriano, M, Mardones, L, Villagran, M, Al-Harrasi, A, Al-Rawahi, A, Cruz-Martins, N, Sharifi-Rad, J, Martorell, M
Frontiers in endocrinology. 2021;:656978
Abstract
Type 2 diabetes Mellitus (T2DM) prevalence has significantly increased worldwide in recent years due to population age, obesity, and modern sedentary lifestyles. The projections estimate that 439 million people will be diabetic in 2030. T2DM is characterized by an impaired β-pancreatic cell function and insulin secretion, hyperglycemia and insulin resistance, and recently the epigenetic regulation of β-pancreatic cells differentiation has been underlined as being involved. It is currently known that several bioactive molecules, widely abundant in plants used as food or infusions, have a key role in histone modification and DNA methylation, and constituted potential epidrugs candidates against T2DM. In this sense, in this review the epigenetic mechanisms involved in T2DM and protein targets are reviewed, with special focus in studies addressing the potential use of phytochemicals as epidrugs that prevent and/or control T2DM in vivo and in vitro. As main findings, and although some controversial results have been found, bioactive molecules with epigenetic regulatory function, appear to be a potential replacement/complementary therapy of pharmacological hypoglycemic drugs, with minimal side effects. Indeed, natural epidrugs have shown to prevent or delay the T2DM development and the morbidity associated to dysfunction of blood vessels, eyes and kidneys due to sustained hyperglycemia in T2DM patients.
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3.
Fast and furious: insights of back splicing regulation during nascent RNA synthesis.
Xue, W, Ma, XK, Yang, L
Science China. Life sciences. 2021;(7):1050-1061
Abstract
Alternative splicing of eukaryotic precursor (messenger) RNAs in the nucleus not only increases transcriptomic complexity, but also expands proteomic and functional diversity. In addition to basic types of alternative splicing, recent transcriptome-wide analyses have also suggested other new types of non-canonical splicing, such as back splicing and recursive splicing, and their widespread expression across species Increasing lines of evidence have suggested mechanisms for back splicing, including insights from analyses of nascent RNA sequencing. In this review, we discuss our current understanding of back splicing regulation, and highlight its distinct characteristics in processing during nascent RNA synthesis by taking advantage of metabolic tagging nascent RNA sequencing. Features of recursive splicing are also discussed in the perspective of nascent RNA sequencing.
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4.
Influence of the Bioactive Diet Components on the Gene Expression Regulation.
Mierziak, J, Kostyn, K, Boba, A, Czemplik, M, Kulma, A, Wojtasik, W
Nutrients. 2021;(11)
Abstract
Diet bioactive components, in the concept of nutrigenetics and nutrigenomics, consist of food constituents, which can transfer information from the external environment and influence gene expression in the cell and thus the function of the whole organism. It is crucial to regard food not only as the source of energy and basic nutriments, crucial for living and organism development, but also as the factor influencing health/disease, biochemical mechanisms, and activation of biochemical pathways. Bioactive components of the diet regulate gene expression through changes in the chromatin structure (including DNA methylation and histone modification), non-coding RNA, activation of transcription factors by signalling cascades, or direct ligand binding to the nuclear receptors. Analysis of interactions between diet components and human genome structure and gene activity is a modern approach that will help to better understand these relations and will allow designing dietary guidances, which can help maintain good health.
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5.
GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin.
Ouyang, J, Isnard, S, Lin, J, Fombuena, B, Peng, X, Chen, Y, Routy, JP
Frontiers in endocrinology. 2020;:581839
Abstract
Weight gain and obesity are global health concerns contributing to morbidity with increased risks of cardiovascular disease, diabetes, liver steatohepatitis and cancer. Pharmacological therapies or bariatric surgery are often required for those who fail to adhere to diet and lifestyle modifications. Metformin, a widely used antidiabetic agent, seems to have a health benefit beyond its anti-hyperglycemic properties, with few side effects. Emerging evidence shows weight loss to be associated with metformin in both diabetic and non-diabetic individuals. Recently, the growth differentiation factor 15 (GDF-15), a member of the transforming growth factor beta superfamily, has been identified as a key mediator of metformin-induced weight loss. Metformin increases the secretion of GDF-15, which binds exclusively to glial cell-derived neurotrophic factor family receptor alpha-like (GFRAL). This gut-brain cytokine works as a prominent player in reducing food intake and body weight in health and disease, like anorexia nervosa and cancer. Herein, we critically review advances in the understanding of the weight-reducing effects of metformin via the GDF-15 pathway.
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6.
Targeting miRNAs by polyphenols: Novel therapeutic strategy for aging.
Majidinia, M, Karimian, A, Alemi, F, Yousefi, B, Safa, A
Biochemical pharmacology. 2020;:113688
Abstract
Regarding the importance of genetic and epigenetic factors in regulation of aging process, different expression pattern of non-coding RNAs in aging could be investigated. Accordingly, micro RNAs (miRNAs) with a wide range of physiological functions as well as a significant footprint in many diseases have been demonstrated to be down or upregulated during the aging process. Therefore, age-associated microRNAs and their targets have potentially detected the accelerated aging and predicted the risks for age-related diseases. Polyphenols as important antioxidants in human dietary observed in fruits and some beverages have beneficial effects on longevity and aging. Considering miRNAs as an interesting mediator in modulating polyphenols' biological effects, targeting miRNAs which is using polyphenols could be a novel strategy for aging.
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7.
Nutrient Control of mRNA Translation.
Shu, XE, Swanda, RV, Qian, SB
Annual review of nutrition. 2020;:51-75
Abstract
The emergence of genome-wide analyses to interrogate cellular DNA, RNA, and protein content has revolutionized the study of control networks that mediate cellular homeostasis. mRNA translation represents the last step of genetic flow and primarily defines the proteome. Translational regulation is thus critical for gene expression, in particular under nutrient excess or deficiency. Until recently, it was unclear how the global effects of translational control are orchestrated by nutrient signaling pathways. An emerging concept of translational reprogramming addresses how to maintain the expression of specific proteins during nutrient stress by translation of selective mRNAs. In this review, we describe recent advances in our understanding of translational control principles; nutrient-sensing mechanisms; and their dysregulation in human diseases such as diabetes, cancer, and aging. The mechanistic understanding of translational regulation in response to different nutrient conditions may help identify potential dietary and therapeutic targets to improve human health.
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8.
The transportome of the malaria parasite.
Martin, RE
Biological reviews of the Cambridge Philosophical Society. 2020;(2):305-332
Abstract
Membrane transport proteins, also known as transporters, control the movement of ions, nutrients, metabolites, and waste products across the membranes of a cell and are central to its biology. Proteins of this type also serve as drug targets and are key players in the phenomenon of drug resistance. The malaria parasite has a relatively reduced transportome, with only approximately 2.5% of its genes encoding transporters. Even so, assigning functions and physiological roles to these proteins, and ascertaining their contributions to drug action and drug resistance, has been very challenging. This review presents a detailed critique and synthesis of the disruption phenotypes, protein subcellular localisations, protein functions (observed or predicted), and links to antimalarial drug resistance for each of the parasite's transporter genes. The breadth and depth of the gene disruption data are particularly impressive, with at least one phenotype determined in the parasite's asexual blood stage for each transporter gene, and multiple phenotypes available for 76% of the genes. Analysis of the curated data set revealed there to be relatively little redundancy in the Plasmodium transportome; almost two-thirds of the parasite's transporter genes are essential or required for normal growth in the asexual blood stage of the parasite, and this proportion increased to 78% when the disruption phenotypes available for the other parasite life stages were included in the analysis. These observations, together with the finding that 22% of the transportome is implicated in the parasite's resistance to existing antimalarials and/or drugs within the development pipeline, indicate that transporters are likely to serve, or are already serving, as drug targets. Integration of the different biological and bioinformatic data sets also enabled the selection of candidates for transport processes known to be essential for parasite survival, but for which the underlying proteins have thus far remained undiscovered. These include potential transporters of pantothenate, isoleucine, or isopentenyl diphosphate, as well as putative anion-selective channels that may serve as the pore component of the parasite's 'new permeation pathways'. Other novel insights into the parasite's biology included the identification of transporters for the potential development of antimalarial treatments, transmission-blocking drugs, prophylactics, and genetically attenuated vaccines. The syntheses presented herein set a foundation for elucidating the functions and physiological roles of key members of the Plasmodium transportome and, ultimately, to explore and realise their potential as therapeutic targets.
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9.
Immunoregulatory Functions of Nuclear Receptors: Mechanisms and Therapeutic Implications.
Zhao, L, Gimple, RC, Yang, Z, Wei, Y, Gustafsson, JÅ, Zhou, S
Trends in endocrinology and metabolism: TEM. 2020;(2):93-106
Abstract
Members of the nuclear receptor superfamily serve as master regulators in signaling by either positively or negatively regulating gene expression. Accumulating evidence has suggested that nuclear receptors are actively involved in immune responses, with specific roles in different immune cell compartments that contribute to both normal function and to disease development. The druggable properties of nuclear receptors have made them ideal modulatory therapeutic targets. Here, we revisit nuclear receptor biology, summarize recent advances in our understanding of the immunological functions of nuclear receptors, describe cell-type-specific roles and specific nuclear receptors in disease pathogenesis, and explore their potential as novel therapeutic targets. These nuclear receptor-dependent alterations in the immune system are amenable to pharmacological manipulation and suggest novel therapeutic strategies.
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10.
Diurnal Rhythmicity Programs of Microbiota and Transcriptional Oscillation of Circadian Regulator, NFIL3.
Kubo, M
Frontiers in immunology. 2020;:552188
Abstract
Circadian rhythms are a very exquisite mechanism to influence on transcriptional levels and physiological activities of various molecules that affect cell metabolic pathways. Long-term alteration of circadian rhythms increases the risk of cardiovascular diseases, hypertension, hypertriglyceridemia, and metabolic syndrome. A drastic change in dietary patterns can affect synchronizing the circadian clock within the metabolic system. Therefore, the interaction between the host and the bacterial community colonizing the mammalian gastrointestinal tract has a great impact on the circadian clock in diurnal programs. Here, we propose that the microbiota regulates body composition through the transcriptional oscillation of circadian regulators. The transcriptional regulator, NFIL3 (also called E4BP4) is a good example. Compositional change of the commensal bacteria influences the rhythmic expression of NFIL3 in the epithelium, which subsequently controls obesity and insulin resistance. Therefore, control of circadian regulators would be a promising therapeutic target for metabolic diseases.