scholarly journals Localization and translocation of mature miRNAs

2021 ◽  
Vol 16 (7) ◽  
pp. 498-507
Author(s):  
A.E. Abaturov ◽  
V.L. Babуch

The scientific review shows the ways of nuclear import and export of miRNAs in the cell. The authors present a clear and accessible scheme of microRNA translocation in the cell. The article shows that the main site of localization in the cytoplasm of cells of the RISC complex and its components, including miRNAs, are processing P-cells. The authors cite the fact that Argonaute proteins — signature components of the effector complex of RISC RNA interference — are localized in mammalian P-bodies. It is shown that proteins of the karyopherin family mediate the translocation of miRISC into the cell nucleus. These proteins recognize nuclear localization sequences (NLS) in the amino acid sequences of proteins and actively transport these proteins through the pores of the cell’s nuclear membrane. It is emphasized that in addition to non-selective mechanisms of nuclear import of miRNAs, there are transport mechanisms that carry certain miRNAs across the cell membrane. Some miRNAs are presented, which are mainly loca­lized in the nucleus of a certain type of cell. Scientists believe that much of the nucleus miRNA is concentrated in polysomes. Export of nuclear pool microRNA into the cytoplasm of the cell occurs with the help of export 1. Thus, in the cytoplasm of the cell, mature forms of microRNA accumulate, some of which are translocated to the cell nucleus or the extracellular space. Assembly of the miRISC complex is carried out in the cytoplasm of the cell, and only after the formation of the complex, it is imported into the cell nucleus. The spectrum of exosome-associated miRNAs can be a highly important diagnostic criterion for some nosologies, and exosomes containing certain miRNAs can be used for targeted therapy of specific diseases. To write the article, information was searched using databases Scopus, Web of Science, MedLine, PubMed, Google Scholar, EMBASE, Global Health, The Cochrane Library, CyberLeninka.

2021 ◽  
Vol 16 (3) ◽  
pp. 257-263
Author(s):  
A.E. Abaturov ◽  
V.L. Babуch

The scientific review presents the biogenesis of miRNAs. To write the article, information was searched using databases Scopus, Web of Science, MedLine, PubMed, Google Scholar, EMBASE, Global Health, The Cochrane Library, CyberLeninka. The article shows the stages of formation of mature miRNAs. It is noted that duplex RNAs resulting from DICER-mediated cleavage interact with Argonaute (AGO) proteins to form an effector RNA-induced silencing complex (RISC). It is shown that the deficiency of AGO proteins leads to a significant decrease in the amount of miRs, and overexpression of AGO proteins is accompanied by an increase in the level of miRs. The main stages of assembling a fully functional RISC are presented. The first stage is the loading of duplex miRs on AGO proteins. The second stage is the promotion of duplex miRs. Human diseases associated with processing disorders in the cytoplasm of the cell are presented. Numerous alternative mechanisms involved in the formation of functionally active miRs are is characterized. There are three classes of mirtrons: typical mirtrons, 5’-tailed mirtrons and 3’-tailed mirtrons. Endogenous csRNAs resemble Drosha-independent synthetic csRNAs used to experimentally induce gene knockout. Chimeric hairpins of non-canonical miR genes are transcribed in tandem or as a part of another type of small RNA gene. Thus, the formation of mature miRs occurs due to the formation of the RISC complex. The core of the RISC complex consists of microRNA, AGO and protein with a trinucleotide repeat 6. Loading dsRNA on AGO proteins and subsequent promotion of duplex RNA are the main stages of assembly of a fully functional RISC. Disorders of processing in the cytoplasm of the cell are associated with the development of some human diseases. There are alternative mechanisms involved in the formation of functionally active miRs: mirtrons, endogenous short RNAs containing hairpins, chimeric hairpins.


2021 ◽  
Vol 16 (4) ◽  
pp. 317-324
Author(s):  
A.E. Abaturov ◽  
V.L. Babуch

This scientific review presents the processes of regulation of miRNA content. To write the article, information was searched using Scopus, Web of Science, MedLine, PubMed, Google Scholar, EMBASE, Global Health, The Cochrane Library, CyberLeninka databases. The article presents the characteristics of the processes of microRNA editing and microRNA tailing, which regulate the content of microRNA through the transcription control. It is emphasized that editing is the most important mechanism of posttranscriptional regulation of microRNA that occurs with the help of RNA-specific adenosine deaminase. The article shows that editing leads to a change in the secondary structure of the microRNA mo­lecule and the deviation of the process of microRNA maturation. It is shown that microRNA tailing is a posttranscriptional elongation of the tail of the molecule by adding nucleotides to the 3’-end of RNA. It has been found that uridinylation is a very common posttranscriptional process that regulates gene expression. The effect of uridinylation on microRNA biogenesis has been demonstrated on the example of the miR let-7 family, which inhibits proliferation and promotes cell differentiation. It has been established that another type of microRNA tailing, namely adeny­lation, most often contri­butes to the stabilization of the molecule, but in some cases can lead to microRNA degradation. Thus, the regulation of miRNA content is carried out by editing miRNA, microRNA tailing. Due to editing, the secondary structure of the microRNA molecule changes and the microRNA maturation process deviates. MicroRNA tailing is a post-transcriptional elongation of the tail of the molecule by ad­ding nucleotides to the 3’-end of RNA by polyuridinylation or poly­a­denylation. Uridinylation affects the processing and degradation of miRNA precursors with different molecular effects, which in some cases contribute to the development of diseases.


VASA ◽  
2016 ◽  
Vol 45 (2) ◽  
pp. 141-147 ◽  
Author(s):  
Jakob Martin Burgstaller ◽  
Johann Steurer ◽  
Ulrike Held ◽  
Beatrice Amann-Vesti

Abstract. Background: Here, we update an earlier systematic review on the preventive efficacy of active compression stockings in patients with diagnosed proximal deep venous thrombosis (DVT) by including the results of recently published trials. The aims are to synthesize the results of the original studies, and to identify details to explain heterogeneous results. Methods: We searched the Cochrane Library, PubMed, Scopus, and Medline for original studies that compared the preventive efficacy of active compression stockings with placebo or no compression stockings in patients with diagnosed proximal DVT. Only randomized controlled trials (RCTs) were included. Results: Five eligible RCTs with a total of 1393 patients (sample sizes ranged from 47 to 803 patients) were included. In three RCTs, patients started to wear compression stockings, placebo stockings or no stockings within the first three weeks after the diagnosis of DVT. The results of two RCTs indicate a statistically significant reduction in post-thrombotic syndrome (PTS) of 50% or more after two or more years. The result of one RCT shows no preventive effect of compression stockings at all. Due to the heterogeneity of the study results, we refrained from pooling the results of the RCTs. In a further RCT, randomization to groups with and without compression stockings took place six months after the diagnosis of DVT, and in another RCT, only patients with the absence of PTS one year after the diagnosis of DVT were analyzed. One RCT revealed a significant reduction in symptoms, whereas another RCT failed to show any benefit of using compression stockings. Conclusions: At this time, it does not seem to be justifiable to entirely abandon the recommendations regarding compression stockings to prevent PTS in patients with DVT. There is evidence favoring compression stockings, but there is also evidence showing no benefit of compression stockings.


2019 ◽  
Vol 2 (2) ◽  
pp. 135-154
Author(s):  
Katja Koelkebeck ◽  
Maja Pantovic Stefanovic ◽  
Dorota Frydecka ◽  
Claudia Palumbo ◽  
Olivier Andlauer ◽  
...  

AbstractObjectivesTo understand and identify factors that promote and prevent research participation among early career psychiatrists (ECPs), in order to understand what would encourage more ECPs to pursue a research career.MethodsWe conducted an electronic search of databases (PubMed and the Cochrane library) using the keywords ‘doctors’, ‘trainees’, ‘residents’, ‘physicians’ and ‘psychiatric trainees’ as well as ‘research’ (MeSH) and ‘publishing’ (MeSH). This search was complemented by a secondary hand search.ResultsWe identified 524 articles, of which 16 fulfilled inclusion criteria for this review. The main barriers included lack of dedicated time for research, lack of mentoring and lack of funding. The main facilitators were opportunities to receive mentorship and access to research funding.ConclusionsAction is needed to counteract the lack of ECPs interested in a career in research. Specific programs encouraging ECPs to pursue research careers and having access to mentors could help increase the current numbers of researching clinicians in the field.


2017 ◽  
Vol 42 (2) ◽  
pp. 149-161
Author(s):  
Henry Cuevas Casa ◽  
Gabriela Aguinaga Romero ◽  
Fabricio González-Andrade

Objetivos: se propone identificar y revisar aquellas estrategias potenciales que incluyan un enfoque multifacético a la hora de hacer frente a la obesidad en niños escolarizados. De acuerdo a la evidencia más reciente, las intervenciones más efectivas para combatir la obesidad infantil son aquellas que involucranactividad física, educación nutricional y entornos de apoyo. Así, en esta revisión nos centramos en buscar dichas intervenciones, que además incluyan seguimientos a medio y largo plazo, monitoreo y evaluación, que son críticos para mantener una acción efectiva.Material y métodos: se incluyó una revisión de artículos científicos publicados en bases de datos especializadas como Pubmed (Medline), the Cochrane Library, The Cochrane Controlled Trials Register (CCTR), ScienceDirect, Scielo, La Biblioteca Cochrane Plus y la página web de la Organización Mundial de la Salud (http://www.who.int).Resultados: de 199 artículos potenciales, sólo 8 fueron incluidos en esta revisión. Los resultados mostraron que aquellas intervenciones multi-componente y de largo plazo tienen beneficios sobre IMC, actividad física y elecciones alimentarias. Sin embargo, pocos estudios mostraron cambios significativos sobrelos hábitos alimentarios generales y sobre la prevalencia de la obesidad. También, se observó que las intervenciones multicomponente que se llevaron a cabo tanto en países en desarrollo de Latinoamérica, como en países desarrollados tuvieron resultados similares.Conclusión: esta revisión demuestra que pueden ocurrir cambios sobre las medidas antropométricas, la actividad física y las elecciones alimentarias cuando se llevan a cabo intervenciones multicomponente en ambientes a nivel de la educación académica primaria, sin importar la localización geográfica, peromanteniendo similar metodología y materiales


2019 ◽  
Vol 65 (5) ◽  
pp. 664-671
Author(s):  
Ilya Pyatnitskiy ◽  
O. Puchkova ◽  
Viktor Gombolevskiy ◽  
Lyudmila Nizovtsova ◽  
Natalya Vetsheva ◽  
...  

The article presents a literature review of the PubMed database and the Cochrane library, aimed at analyzing the current situation and problems in the field of breast cancer screening in the world and Russia to form an idea of the key elements in organizing an effective screening program in the Russian healthcare system, as well as the possibilities of using new technologies when organizing such programs.


2020 ◽  
Vol 17 (5) ◽  
pp. 472-486
Author(s):  
Lucy Beishon ◽  
Kannakorn Intharakham ◽  
David Swienton ◽  
Ronney B. Panerai ◽  
Thompson G. Robinson ◽  
...  

Background: Cognitive Training (CT) has demonstrated some benefits to cognitive and psychosocial function in Mild Cognitive Impairment (MCI) and early dementia, but the certainty related to those findings remains unclear. Therefore, understanding the mechanisms by which CT improves cognitive functioning may help to understand the relationships between CT and cognitive function. The purpose of this review was to identify the evidence for neuroimaging outcomes in studies of CT in MCI and early Alzheimer’s Disease (AD). Methods: Medline, Embase, Web of Science, PsycINFO, CINAHL, and The Cochrane Library were searched with a predefined search strategy, which yielded 1778 articles. Studies were suitable for inclusion where a CT program was used in patients with MCI or AD, with a structural or functional Magnetic Resonance Imaging (MRI) outcome. Studies were assessed for quality using the Downs and Black criteria. Results: Medline, Embase, Web of Science, PsycINFO, CINAHL, and The Cochrane Library were searched with a predefined search strategy, which yielded 1778 articles. Studies were suitable for inclusion where a CT program was used in patients with MCI or AD, with a structural or functional Magnetic Resonance Imaging (MRI) outcome. Studies were assessed for quality using the Downs and Black criteria. Conclusions: CT resulted in variable functional and structural changes in dementia, and conclusions are limited by heterogeneity and study quality. Larger, more robust studies are required to correlate these findings with clinical benefits from CT.


Author(s):  
Hamish Farquhar ◽  
Ana B Vargas-Santos ◽  
Huai Leng Pisaniello ◽  
Mark Fisher ◽  
Catherine Hill ◽  
...  

Abstract Objectives To evaluate the efficacy, defined as achieving target serum urate <6.0 mg/dl, and safety of urate-lowering therapies (ULT) for people with gout and CKD stages 3–5. Methods PubMed, The Cochrane Library, and EMBASE, were searched from 1 January 1959 to 31 January 2018 for studies that enrolled people with gout, who had an estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) of < 60 mL/min, and exposure to allopurinol, febuxostat, probenecid, benzbromarone, lesinurad or pegloticase. All study designs other than case reports were included, except for people on dialysis, for which we did include case reports. Results There were 36 reports with an analysis of efficacy and/or safety based upon renal function – allopurinol (n = 12), febuxostat (n = 10), probenecid (n = 3), benzbromarone (n = 5), lesinurad (n = 5), and pegloticase (n = 1). There were 108 reports that involved people with gout and renal impairment but did not contain any analysis on efficacy and/or safety based upon renal function – allopurinol (n = 84), febuxostat (n = 14), benzbromarone (n = 1), lesinurad (n = 3), and pegloticase (n = 6). Most studies excluded people with more severe degrees of renal impairment (eGFR or CrCl of < 30mL/min). For allopurinol in particular, there was significant variability in the dose of drug used, and efficacy in terms of urate lowering, across all levels of renal impairment. Conclusion There is a lack of evidence regarding efficacy and/or safety of currently used ULT according to different levels of renal function. Future studies should include patients with CKD and should report study outcomes stratified by renal function.


Pharmacology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Shan Deng ◽  
Yonghao Yu

Patients who undergo surgery of femur fracture suffer the excruciating pain. Dexmedetomidine (DEX) is a unique α2-adrenergic receptor agonist with sedative and analgesic properties, whose efficacy and safety are still unclear for surgery of femur fracture. Randomized controlled trials comparing the effects of addition of DEX to general or local anesthesia in surgery of femur fracture were searched from MEDLINE, EMBASE, and the Cochrane Library database. Patients who received DEX infusion had a significant longer time to rescue analgesia compared with those without DEX coadministration. DEX treatment seemed to reduce the visual analog score; however, the significance did not reach any statistical difference. DEX as an analgesic adjuvant did not reduce the onset of sensory block time, shorten the time to achieve maximum sensory block level, and provide a longer duration of sensory block. The difference in mean sedation scores between 2 groups was not statistically significant. As for adverse effects, DEX therapy significantly increased the rate of hypotension. In conclusion, dexmedetomidine as a local anesthetic adjuvant in femur fracture surgery had a longer duration of rescue analgesia. However, the incidence of hypotension was markedly increased in these patients. It was worth noting that the evidence was of low to moderate quality.


2021 ◽  
pp. 174749302110042
Author(s):  
Grace Mary Turner ◽  
Christel McMullan ◽  
Olalekan Lee Aiyegbusi ◽  
Danai Bem ◽  
Tom Marshall ◽  
...  

Aims To investigate the association between TBI and stroke risk. Summary of review We undertook a systematic review of MEDLINE, EMBASE, CINAHL, and The Cochrane Library from inception to 4th December 2020. We used random-effects meta-analysis to pool hazard ratios (HR) for studies which reported stroke risk post-TBI compared to controls. Searches identified 10,501 records; 58 full texts were assessed for eligibility and 18 met the inclusion criteria. The review included a large sample size of 2,606,379 participants from four countries. Six studies included a non-TBI control group, all found TBI patients had significantly increased risk of stroke compared to controls (pooled HR 1.86; 95% CI 1.46-2.37). Findings suggest stroke risk may be highest in the first four months post-TBI, but remains significant up to five years post-TBI. TBI appears to be associated with increased stroke risk regardless of severity or subtype of TBI. There was some evidence to suggest an association between reduced stroke risk post-TBI and Vitamin K antagonists and statins, but increased stroke risk with certain classes of antidepressants. Conclusion TBI is an independent risk factor for stroke, regardless of TBI severity or type. Post-TBI review and management of risk factors for stroke may be warranted.


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