scholarly journals Roles of LncRNAs in Regulating Mitochondrial Dysfunction in Septic Cardiomyopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuang Liu ◽  
Wei Chong

Sepsis is an abnormal systemic inflammatory response of the host immune system to infection and can lead to fatal multiorgan dysfunction syndrome. Epidemiological studies have shown that approximately 10-70% of sepsis cases can lead to septic cardiomyopathy. Since the pathogenesis of septic cardiomyopathy is not clear, it is difficult for medical doctors to treat the disease. Therefore, finding effective interventions to prevent and reduce myocardial damage in septic cardiomyopathy is clinically significant. Epigenetics is the study of stable genetic phenotype inheritance that does not involve changing gene sequences. Epigenetic inheritance is affected by both gene and environmental regulation. Epigenetic studies focus on the modification and influence of chromatin structure, mainly including chromatin remodelling, DNA methylation, histone modification and noncoding RNA (ncRNA)-related mechanisms. Recently, long ncRNA (lncRNA)-related mechanisms have been the focus of epigenetic studies. LncRNAs are expected to become important targets to prevent, diagnose and treat human diseases. As the energy metabolism centre of cells, mitochondria are important targets in septic cardiomyopathy. Intervention measures to prevent and treat mitochondrial damage are of great significance for improving the prognosis of septic cardiomyopathy. LncRNAs play important roles in life activities. Recently, studies have focused on the involvement of lncRNAs in regulating mitochondrial dysfunction. However, few studies have revealed the involvement of lncRNAs in regulating mitochondrial dysfunction in septic cardiomyopathy. In this article, we briefly review recent research in this area.

2001 ◽  
Vol 15 (11) ◽  
pp. 1993-2009 ◽  
Author(s):  
Melanie R. Ginger ◽  
Maria F. Gonzalez-Rimbau ◽  
Jason P. Gay ◽  
Jeffrey M. Rosen

Abstract Epidemiological studies have consistently shown that an early full-term pregnancy is protective against breast cancer. We hypothesize that the hormonal milieu that is present during pregnancy results in persistent changes in the pattern of gene expression in the mammary gland, leading to permanent changes in cell fate that determine the subsequent proliferative response of the gland. To investigate this hypothesis, we have used suppression subtractive hybridization to identify genes that are persistently up-regulated in the glands of E- and progesterone (P)-treated Wistar-Furth rats 28 d after steroid hormone treatment compared with age-matched virgins. Using this approach, a number of genes displaying persistent altered expression in response to previous treatment with E and P were identified. Two markers have been characterized in greater detail: RbAp46 and a novel gene that specifies a noncoding RNA (designated G.B7). Both were persistently up-regulated in the lobules of the regressed gland and required previous treatment with both E and P for maximal persistent expression. RbAp46 has been implicated in a number of complexes involving chromatin remodeling, suggesting a mechanism whereby epigenetic factors responsible for persistent changes in gene expression may be related to the determination of cell fate. These results provide the first support at the molecular level for the hypothesis that hormone-induced persistent changes in gene expression are present in the involuted mammary gland.


2021 ◽  
Vol 16 (7-8) ◽  
pp. 106-109
Author(s):  
L.O. Malsteva ◽  
W.W. Nikonov ◽  
N.A. Kazimirova ◽  
A.A. Lopata

The review aims to present the chronological sequence of developing universal definitions of myocardial infarction, new ideas for improving the screening of post-infectious and sepsis-associated myocardial infarction (MI) (casuistic masks of myocardial infarction). The stages of the development of the common and global definition of myocardial infarction are outlined: 1 — by WHO working groups based on ECG for epidemiological studies; 2 — by the European Society of Cardiology and the American College of Cardio-logy using clinical and biochemical approaches; 3 — the Global Task Force consensus document of universal definition with subsequent classification of MI into five subtypes (spontaneous, dissonance in oxygen delivery and consumption; lethal outcome before the rise of specific markers of myocardial damage; PCI-associated; CABG- associated); 4 — review by the Joint Task Force of the above document based on the inclusion of more sensitive markers — troponins; 5 — the allocation of 17 non-ischemic myocardial damage, accompanied by an increase in the level of troponin; 6 — characteristic of the atrial natriuretic peptide from the standpoint of its synthesis, storage, release, diagnostic value as a biomarker of acute myocardial dama­ge; 7 — a clinical definition of myocardial infarction, presented in materials of the III Consensus on myocardial infarction 2017. The diagnosis of myocardial infarction using the criteria set in this document requires the integration of clinical data, ECG patterns, laboratory data, imaging findings, and, in some cases, pathological results, which are considered in the context of the time frame of the suspec­ted event. K. Thygesen et al. consider the additional use of: 1) cardiovascular magnetic resonance to determine the etiology of myocardial damage; 2) computer coronary angiography with suspected myocardial infarction. Myocardial infarction is a combination of specific cardio markers with at least one of the symptoms listed above. The formation of myocardial infarction can occur during/after acute respiratory infection. Causal relationships between these two states are established. Post-infectious myocardial infarction is strongly recommended to be individualized as a separate diagnostic entity. In sepsis, global myocardial ischemia with ischemic myocardial damage arises as a result of humoral and cellular factors, accompanied by an increase in troponins, a decrease in the ejection fraction of the left ventricle by 45 % and an increase in the final diastolic size of the left ventricle, the development of sepsis-associated multiple organ fai­lure, which is an unfavourable prognosis factor.


2020 ◽  
Vol 42 (12) ◽  
pp. 1097-1103
Author(s):  
Judy Frain ◽  
Horng-Shiuann Wu ◽  
Ling Chen

Studies analyzing depressive symptoms across chronic disease populations are limited. Our descriptive comparison investigation included two studies on life-limiting conditions: Human Immunodeficiency Virus (HIV) and breast cancer. In both, depressive symptoms were assessed using the Center for Epidemiological Studies Depression Scale (CES-D). We found a mean depression score of 18.1 (± 11.8) overall ( N = 243). Over half (54%) reported clinically significant depressive symptoms (CES-D ≥ 16); 26% reported severe depressive symptoms (CES-D > 24). Disease and years of education were predictors of depressive symptoms. Persons living with breast cancer showed significantly worse depressive symptoms than persons living with HIV (p < 0.0001). After adjusting for disease, fewer years of education predicted worse depressive symptoms (p < 0.0001). This study demonstrated common determinants of depressive symptoms in both disease populations, suggesting that underlying conditions known to be predictors of depression could be assessed to identify those at higher risk for depression.


2010 ◽  
Vol 41 (3) ◽  
pp. 619-627 ◽  
Author(s):  
T. Charman ◽  
A. Pickles ◽  
E. Simonoff ◽  
S. Chandler ◽  
T. Loucas ◽  
...  

BackgroundAutism spectrum disorder (ASD) was once considered to be highly associated with intellectual disability and to show a characteristic IQ profile, with strengths in performance over verbal abilities and a distinctive pattern of ‘peaks’ and ‘troughs’ at the subtest level. However, there are few data from epidemiological studies.MethodComprehensive clinical assessments were conducted with 156 children aged 10–14 years [mean (s.d.)=11.7 (0.9)], seen as part of an epidemiological study (81 childhood autism, 75 other ASD). A sample weighting procedure enabled us to estimate characteristics of the total ASD population.ResultsOf the 75 children with ASD, 55% had an intellectual disability (IQ<70) but only 16% had moderate to severe intellectual disability (IQ<50); 28% had average intelligence (115>IQ>85) but only 3% were of above average intelligence (IQ>115). There was some evidence for a clinically significant Performance/Verbal IQ (PIQ/VIQ) discrepancy but discrepant verbalversusperformance skills were not associated with a particular pattern of symptoms, as has been reported previously. There was mixed evidence of a characteristic subtest profile: whereas some previously reported patterns were supported (e.g. poor Comprehension), others were not (e.g. no ‘peak’ in Block Design). Adaptive skills were significantly lower than IQ and were associated with severity of early social impairment and also IQ.ConclusionsIn this epidemiological sample, ASD was less strongly associated with intellectual disability than traditionally held and there was only limited evidence of a distinctive IQ profile. Adaptive outcome was significantly impaired even for those children of average intelligence.


2021 ◽  
Author(s):  
Aditi Shukla ◽  
Roberto Perales ◽  
Scott Kennedy

AbstractNoncoding RNAs have emerged as mediators of transgenerational epigenetic inheritance (TEI) in a number of organisms. A robust example of RNA-directed TEI is the inheritance of gene silencing states following RNA interference (RNAi) in the metazoan C. elegans. During RNAi inheritance, gene silencing is transmitted by a self-perpetuating cascade of siRNA-directed poly(UG) tailing of mRNA fragments (pUGylation), followed by siRNA synthesis from poly(UG)-tailed mRNA templates (termed pUG RNA/siRNA cycling). Despite the self-perpetuating nature of pUG RNA/siRNA cycling, RNAi inheritance is finite, suggesting that systems likely exist to prevent permanent RNAi-triggered gene silencing. Here we show that, in the absence of Piwi-interacting RNAs (piRNAs), an animal-specific class of small noncoding RNA, RNAi-based gene silencing can become essentially permanent, lasting at near 100% penetrance for more than five years and hundreds of generations. This permanent gene silencing is mediated by perpetual activation of the pUG RNA/siRNA TEI pathway. Further, we find that piRNAs coordinate endogenous RNAi pathways to prevent germline-expressed genes, which are not normally subjected to TEI, from entering a state of permanent and irreversible epigenetic silencing also mediated by perpetual activation of pUG RNA/siRNA cycling. Together, our results show that one function of C. elegans piRNAs is to insulate germline-expressed genes from aberrant and runaway inactivation by the pUG RNA/siRNA epigenetic inheritance system.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Pan Wu ◽  
Xiao Yu ◽  
Yue Peng ◽  
Qian-Lu Wang ◽  
Long-Tian Deng ◽  
...  

Abstract Background Studies have shown that ginsenoside R3 (Rg3) plays a protective role in sepsis-induced organ injuries and mitochondrial dysfunction. Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) is regarded as a regulator in sepsis. However, the association between TUG1 and Rg3 remains elusive. Methods A sepsis mouse model was established by caecal ligation and puncture (CLP), and liver injury was induced by haematoxylin-eosin (H&E) staining. Lipopolysaccharide (LPS) was used to induce hepatocyte damage. The expression levels of TUG1, microRNA (miR)-200a-3p, and silencing information regulator 1 (SIRT1) were examined by quantitative real-time polymerase chain reaction (qRT–PCR) assays. Cell viability was monitored using the Cell Counting Kit-8 (CCK-8) assay. MitoSOX Red staining and CBIC2 (JC-1) dye were employed to detect mitochondrial reactive oxygen species (ROS) and mitochondrial transmembrane potential (MTP) levels, respectively. The interaction between miR-200a-3p and TUG1 or SIRT1 was confirmed via dual-luciferase reporter or RNA immunoprecipitation (RIP) assay. Results Rg3 upregulated TUG1 expression in liver tissues of CLP mice and LPS-induced hepatocytes. Rg3 could activate autophagy to improve mitochondrial dysfunction in LPS-treated hepatocytes, which was partially reversed by TUG1 depletion or miR-200a-3p overexpression. Importantly, TUG1 targeted miR-200a-3p to activate the SIRT1/AMP-activated protein kinase (AMPK) pathway in LPS-treated hepatocytes. Moreover, gain of TUG1 ameliorated mitochondrial dysfunction in LPS-treated hepatocytes by sequestering miR-200a-3p. Conclusion Our study revealed that Rg3 increased TUG1 expression and reduced miR-200a-3p expression to stimulate the SIRT1/AMPK pathway, thereby enhancing autophagy to improve sepsis-induced liver injury and mitochondrial dysfunction.


2021 ◽  
Vol 34 ◽  
Author(s):  
Mayara Thais Correr Ribeiro ◽  
Luzia Iara Pfeifer

Abstract Introduction: The cerebral palsy and brachial plexus injury may cause asymmetry in the use of the upper limbs (UL). This condition requires early treatment to reduce the impact of the child's life; therefore, several proposed interventions aim to increase their functional independence. The Constraint-Induced Movement Therapy (CIMT) and Hand-Arm Bimanual Intensive Therapy (HABIT) have been widely considered effective interventions to improve hand function. Objective: Investigate the effects of an intervention protocol based on the CIMT and HABIT theoretical foundations in the stimulation of manual function in infants with the UL asymmetry. Methods: Five infants (6-24 months) participated in the study. To evaluate the motor function of infants we used Pediatric Motor Activity Log (PMAL-R) and Manual Function Evaluation (AMIGO), and to assess the caregiver's perception of the participation of the infant in daily tasks, we used the Pediatric Disability Assessment Inventory (PEDI). All evaluations occurred before, immediately after the intervention, and after four months for follow-up recording, and were analyzed descriptively by Jacobson- Truax method. Results: The results between evaluation and reevaluation demonstrated evolution in all aspects studied. In the PEDI self-care session, an average of 38.6 (±8.4) - 44.2 (±7.4); PEDI Mobility: 28.8 (±20.3) - 36.28 (±21.7); PEDI Social Function: 40.1 (±10.2) - 42.3 (±8.9). The PMAL-R quantity and quality results evidence a highly positive clinical significance in all infants. Conclusion: The application of the modified restriction intervention protocol resulted in reliable and clinically significant changes in all cases.


2019 ◽  
Vol 27 (1) ◽  
Author(s):  
Luis Furuya-Kanamori ◽  
Jennifer Stone ◽  
Laith Yakob ◽  
Martyn Kirk ◽  
Peter Collignon ◽  
...  

Abstract Background Recent studies have shown that over 50% of people travelling to Southeast Asia return colonized with multidrug-resistant Enterobacterales (MRE) including carbapenemase-producing Enterobacterales. Importation of MRE by travellers and subsequent spread to family members, communities and healthcare facilities poses real risks that have not yet been adequately assessed. This systematic review and meta-analysis aims to quantify the risk factors and interventions for reducing the risk of MRE acquisition among international travellers. Methods A systematic search was conducted in PubMed, Web of Science and Scopus for analytical epidemiological studies containing data post-2000 that assessed the risk factors to acquire and/or interventions to reduce the risk of MRE acquisition in travellers. Two researchers independently screened all the studies and extracted the information, and disagreements were resolved through consensus. The proportions of MRE acquisition by the region of destination and the odds ratio (OR) for the different risk factors and/or interventions were pooled using the inverse variance heterogeneity model. Results A total of 20 studies (5253 travellers from high-income countries) were included in the meta-analysis. South Asia [58.7%; 95% confidence interval (CI), 44.5–72.5%] and Northern Africa (43.9%; 95% CI 37.6–50.3%) were the travel destinations with the highest proportion of MRE acquisition. Inflammatory bowel disease (OR 2.1; 95% CI 1.2–3.8), use of antibiotics (OR 2.4; 95% CI 1.9–3.0), traveller’s diarrhoea (OR 1.7; 95% CI 1.3–2.3) and contact with the healthcare system overseas (OR 1.5; 95% CI 1.1–2.2) were associated with MRE colonization. Vegetarians (OR 1.4; 95% CI 1.0–2.0) and backpackers (OR 1.5; 95% CI 1.2–1.8) were also at increased odds of MRE colonization. Few studies (n = 6) investigated preventive measures and found that consuming only bottled water/beverages, meticulous hand hygiene and probiotics had no protective effect on MRE colonization. Conclusions International travel is an important driver for MRE spread worldwide. Future research needs to identify effective interventions to reduce the risk of MRE acquisition as well as design strategies to reduce local transmission on return.


2016 ◽  
Vol 22 (1) ◽  
pp. 6
Author(s):  
Nwaonu C. Nwakanma ◽  
John N. Ofoedu

<p><strong>Objectives:</strong> The aim of this study was to investigate the relationship between erectile dysfunction (ED), marital adjustment and depression. <br /><strong>Methods:</strong> The survey was conducted among primary care patients at Federal Medical Centre, Umuahia. Subjects were 678 married, male primary care patients; aged 20–70 years (mean age = 45 years). ED was assessed by International Index of Erectile Function 5 (IIEF-5) score, the presence of clinically significant depressive symptoms was assessed with the 5-item <br />version of the Center for Epidemiological Studies Depression Scale (CES-D), and marital adjustment was assessed with the Revised Dyadic Adjustment Scale (RDAS).<br /><strong>Results:</strong> The prevalence of probable depression by CES-D and ED by IIEF-5 score was 20.9% and 26.0%, respectively. Marital distress was rampant (62.0%) among subjects with ED (<em>p</em> &lt; 0.05, <em>χ</em>2 = 196.58). Erectile dysfunction was associated with marital adjustment (<em>p</em> &lt; 0.05). Partial correlation revealed that depression affects both ED and marital adjustment, and is closely related to both variables.<br /><strong>Conclusion:</strong> Partner involvement and screening for depression should be emphasised in the care of patients with ED.</p>


2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Arthur Durand ◽  
Thibault Duburcq ◽  
Thibault Dekeyser ◽  
Remi Neviere ◽  
Michael Howsam ◽  
...  

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It remains a leading cause of death worldwide, despite the development of various therapeutic strategies. Cardiac dysfunction, also referred to as septic cardiomyopathy, is a frequent and well-described complication of sepsis and associated with worse clinical outcomes. Recent research has increased our understanding of the role of mitochondrial dysfunction in the pathophysiology of septic cardiomyopathy. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions.


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