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The Effects of Trauma on Brain and Body
Published in Mark B. Constantian, Childhood Abuse, Body Shame, and Addictive Plastic Surgery, 2018
Epigenetic changes have ramifications. Histone modifications, RNA “silencing” (or non-expression of short RNA segments), and DNA “methylation”—adding a methyl groups (CH3-) to susceptible cytosine nucleotides at their phosphate/guanine nucleotide connection (“CpG” site)—have been varyingly associated with colorectal and prostate cancer development. Both methylation and demethylation are associated with coronary artery disease, schizophrenia, depression,163,164 and with congenital anomalies attributable to nutritional deficiencies.165 Cytokines, growth factors, stress hormone and neurotrophic factor levels all modulate according to stresses placed on the organism through epigenetic modifiers.
Genetics of Endocrine Tumours
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Waseem Ahmed, Prata Upasna, Dae Kim
MicroRNAs are small non-coding RNA genes (containing about 22 nucleotides) that function in RNA silencing and post-translational regulation of gene expression. MicroRNAs deregulation in MTC is thought to be an early event in parafollicular C-cell carcinogenesis.55
Recent Advances In HIV/AIDS
Published in Anne George, K. S. Joshy, Mathew Sebastian, Oluwatobi Samuel Oluwafemi, Sabu Thomas, Holistic Approaches to Infectious Diseases, 2017
Small interfering RNA (siRNA) is small RNA of 18-25 nucleotides (nt) in length that play important role in regulating gene expression. It is incorporated into an RNA-induced silencing complex (RISC) and serves as guides for silencing their corresponding target mRNAs based on complementary base-pairing. The promise of gene silencing has led many researchers to consider siRNA as an anti-viral load tool. However, in long-term settings, many viruses appear to escape from this therapeutical strategy. HIV sets a very good example in evading RNA silencing, by either mutating the siRNA-targeted sequence or by encoding for a partial suppressor of RNAi (RNA interference) (Man et al., 2005).
Small interfering RNA-based nanotherapeutics for treating skin-related diseases
Published in Expert Opinion on Drug Delivery, 2023
Yen-Tzu Chang, Tse-Hung Huang, Ahmed Alalaiwe, Erica Hwang, Jia-You Fang
RNA silencing is a promising and novel therapy for targeting skin diseases such as psoriasis, cutaneous malignancy, and cutaneous wounds. Efficient and safe delivery of siRNAs is of paramount importance for exploitation in clinical applications, as naked siRNAs are susceptible to biodegradation. Poor delivery into the skin barrier and cell membrane is also a challenge of RNAi-based therapy. The application of RNAi to the skin is still limited due to insufficient siRNA absorption and off-target effects. The elaboration of siRNA delivery carriers that enhance skin delivery and cell internalization is urgent. Considering the efficiency of skin permeation and controlled release, the intervention of nanocarriers for siRNA delivery can be a potential solution for skin disease treatment. In this review, the development and application of different nanosystems have been highlighted to show successful siRNA delivery for mitigating skin-related disorders. The delivery of nanoparticulate siRNA to the skin increased nucleic acid accumulation in the nidus site, enhanced uptake by cells, and thus effectively resolved the cutaneous pathogenesis of different skin diseases. The success of the clinical adaptation of RNAi-based nanotherapeutics for skin disorder management can be expected in the future based on past and current evidence about the design of topical siRNA nanodelivery systems.
Inclisiran: a small interfering RNA strategy targeting PCSK9 to treat hypercholesterolemia
Published in Expert Opinion on Drug Safety, 2022
Yajnavalka Banerjee, Anca Pantea Stoian, Arrigo Francesco Giuseppe Cicero, Federica Fogacci, Dragana Nikolic, Alexandros Sachinidis, Ali A. Rizvi, Andrej Janez, Manfredi Rizzo
siRNAs are small dsRNAs (19–25 bp) that do not code to translate any molecule; they are significant mediators of the RNAi process, representing a novel therapeutic platform to exploit the natural mechanism of RNAi to inhibit protein synthesis. They are exogenously transfected into the cell and further incorporated into the RNAi machinery. Long dsRNAs, transfected in low concentrations to avoid immune response through the activation of the interferon pathway, are cleaved by Dicer, which is a dsRNA-specific ribonuclease, into 21–25 nucleotide-long ds siRNAs with two nucleotides in their 3ʹ overhang and 5ʹ phosphate groups. siRNAs are further recognized by the Argonaute 2 (AGO2) (a protein with a key role in RNA silencing) and RNA-induced silencing complex (RISC) (a multiribonucleoprotein complex) and unwind into their single-strand components [21–23]. The sense strand is degraded, and its complement-antisense strand binds via nucleotide complementarity targeting mRNA sequence. This is cleaved by AGO2 and degraded by exonucleases [24,25]. The result of such an association is solely dependent on the complementarity between siRNA and the target gene [26]. Although siRNAs have a specific target gene, they can also knock down unintended genes in two ways: (1) either deficient complementarity to non-targeted mRNAs or (2) by entering the endogenous miRNA machinery [26].
Dioxin and endometriosis: a new possible relation based on epigenetic theory
Published in Gynecological Endocrinology, 2020
Pierluigi Giampaolino, Luigi Della Corte, Virginia Foreste, Fabio Barra, Simone Ferrero, Giuseppe Bifulco
A microRNA (miRNA) is a small non-coding RNA molecule (containing about 22 nucleotides) that functions in RNA silencing and post-transcriptional regulation of gene expression. Over 50 miRNAs have been shown in many studies to be differentially expressed in endometriotic cells, even if researches vary in which miRNAs they focused and which direction their expression patterns change [65]. Recent papers have demonstrated the possibility of using specific miRNAs as serum biomarkers for diagnosis of endometriosis considering the presence of different levels of some miRNA markers in the circulation of endometriosis patients [66]: in a retrospective study, the expression of 4 miRNAs (miR-199a, miR-122, miR-145, and miR-542-3p) predicted endometriosis with 93.2% sensitivity and 96% specificity [67]. Identifying useful miRNA biomarkers could support in the appropriate diagnosis and treatment of endometriosis.