scholarly journals Cellular and extracellular miRNAs are blood-compartment-specific diagnostic targets in sepsis

2017 ◽  
Vol 21 (10) ◽  
pp. 2403-2411 ◽  
Author(s):  
Marlene Reithmair ◽  
Dominik Buschmann ◽  
Melanie Märte ◽  
Benedikt Kirchner ◽  
Daniel Hagl ◽  
...  
2005 ◽  
Vol 99 (2) ◽  
pp. 499-504 ◽  
Author(s):  
Ralph Beneke ◽  
Matthias Hütler ◽  
Marcus Jung ◽  
Renate M. Leithäuser

Whether age-related differences in blood lactate concentrations (BLC) reflect specific BLC kinetics was analyzed in 15 prepubescent boys (age 12.0 ± 0.6 yr, height 1.54 ± 0.06 m, body mass 40.0 ± 5.2 kg), 12 adolescents (16.3 ± 0.7 yr, 1.83 ± 0.07 m, 68.2 ± 7.5 kg), and 12 adults (27.2 ± 4.5 yr, 1.83 ± 0.06 m, 81.6 ± 6.9 kg) by use of a biexponential four-parameter kinetics model under Wingate Anaerobic Test conditions. The model predicts the lactate generated in the extravasal compartment (A), invasion ( k1), and evasion ( k2) of lactate into and out of the blood compartment, the BLC maximum (BLCmax), and corresponding time (TBLCmax). BLCmax and TBLCmax were lower ( P < 0.05) in boys (BLCmax 10.2 ± 1.3 mmol/l, TBLCmax 4.1 ± 0.4 min) than in adolescents (12.7 ± 1.0 mmol/l, 5.5 ± 0.7 min) and adults (13.7 ± 1.4 mmol/l, 5.7 ± 1.1 min). No differences were found in A related to the muscle mass (AMM) and k1 between boys (AMM: 22.8 ± 2.7 mmol/l, k1: 0.865 ± 0.115 min−1), adolescents (22.7 ± 1.3 mmol/l, 0.692 ± 0.221 min−1), and adults (24.7 ± 2.8 mmol/l, 0.687 ± 0.287 min−1). The k2 was higher ( P < 0.01) in boys (2.87 10−2 ± 0.75 10−2 min−1) than in adolescents (2.03 × 10−2 ± 0.89 × 10−2 min−1) and adults (1.99 × 10−2 ± 0.93 × 10−2 min−1). Age-related differences in the BLC kinetics are unlikely to reflect differences in muscular lactate or lactate invasion but partly faster elimination out of the blood compartment.


2021 ◽  
Vol 22 (22) ◽  
pp. 12303
Author(s):  
Hiroaki Konishi ◽  
Hiroki Sato ◽  
Kenji Takahashi ◽  
Mikihiro Fujiya

MicroRNAs (miRNAs) are single-stranded short-chain RNAs that are endogenously expressed in vertebrates; they are considered the fine-tuners of cellular protein expression that act by modifying mRNA translation. miRNAs control tissue development and differentiation, cell growth, and apoptosis in cancer and non-cancer cells. Aberrant regulation of miRNAs is involved in the pathogenesis of various diseases including cancer. Numerous investigations have shown that the changes in cellular miRNA expression in cancerous tissues and extracellular miRNAs enclosed in exosomes are correlated with cancer prognosis. Therefore, miRNAs can be used as cancer biomarkers and therapeutic targets for cancer in clinical applications. In the previous decade, miRNAs have been shown to regulate cellular functions by directly binding to proteins and mRNAs, thereby controlling cancer progression. This regulatory system implies that cancer-associated miRNAs can be applied as molecular-targeted therapy. This review discusses the roles of miRNA–protein systems in cancer progression and its future applications in cancer treatment.


2006 ◽  
Vol 290 (6) ◽  
pp. F1295-F1302 ◽  
Author(s):  
Stan F. J. van de Graaf ◽  
Joost G. J. Hoenderop ◽  
René J. M. Bindels

The epithelial Ca2+ channels TRPV5 and TRPV6 are the most Ca2+-selective members of the TRP channel superfamily. These channels are the prime target for hormonal control of the active Ca2+ flux from the urine space or intestinal lumen to the blood compartment. Insight into their regulation is, therefore, pivotal in our understanding of the (patho)physiology of Ca2+ homeostasis. The recent elucidation of TRPV5/6-associated proteins has provided new insight into the molecular mechanisms underlying the regulation of these channels. In this review, we describe the various means of TRPV5/6 regulation, the role of channel-associated proteins herein, and the relationship between both processes.


2019 ◽  
Vol 30 (4) ◽  
pp. 656-673 ◽  
Author(s):  
Marcelo A. Mori ◽  
Raissa G. Ludwig ◽  
Ruben Garcia-Martin ◽  
Bruna B. Brandão ◽  
C. Ronald Kahn
Keyword(s):  

Open Biology ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 180212 ◽  
Author(s):  
Bing Chen ◽  
Zijing Xia ◽  
Ya-Nan Deng ◽  
Yanfang Yang ◽  
Peng Zhang ◽  
...  

MicroRNAs (miRNAs) are one abundant class of small, endogenous non-coding RNAs, which regulate various biological processes by inhibiting expression of target genes. miRNAs have important functional roles in carcinogenesis and development of colorectal cancer (CRC), and emerging evidence has indicated the feasibility of miRNAs as robust cancer biomarkers. This review summarizes the progress in miRNA-related research, including study of its oncogene or tumour-suppressor roles and the advantages of miRNA biomarkers for CRC diagnosis, treatment and recurrence prediction. Along with analytical technique improvements in miRNA research, use of the emerging extracellular miRNAs is feasible for CRC diagnosis and prognosis.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Meng Li ◽  
Junping Zhang

MicroRNAs (miRNAs) are composed of a group of endogenous and noncoding small RNAs which control expression of complementary target mRNAs. The extended functions of miRNAs enhance the complexity of gene-regulatory processes in cardiovascular and cerebrovascular diseases. Indeed, recent studies have shown that miRNAs are closely related to myocardial infarction, heart failure, atrial fibrillation, cardiomyopathy, hypertension, angiogenesis, coronary artery disease, dyslipidaemia, stroke, and so forth. These findings suggest a new therapeutic pointcut for cardiovascular and cerebrovascular diseases and show the extensive therapeutic potential of miRNA regulation. Moreover, it has been shown that circulating extracellular miRNAs are stable in bodily fluids, which indicates circulating miRNAs as potential and emerging biomarkers for noninvasive diagnosis. This review highlights the most recent findings indicative of circulating miRNAs as potential clinical biomarkers for diagnosis of cardiovascular and cerebrovascular diseases.


Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3455
Author(s):  
Blanca Ortiz-Quintero

MicroRNAs (miRNAs) are released by different types of cells through highly regulated mechanisms under normal and pathological conditions. These extracellular miRNAs can be delivered into recipient cells for functional purposes, acting as cell-to-cell signaling mediators. It has been discovered that cancer cells release miRNAs into their surroundings, targeting normal cells or other cancer cells, presumably to promote tumor development and progression. These extracellular miRNAs are associated with oncogenic mechanisms and, because they can be quantified in blood and other bodily fluids, may be suitable noninvasive biomarkers for cancer detection. This review summarizes recent evidence of the role of extracellular miRNAs as intercellular mediators, with an emphasis on their role in the mechanisms of tumor development and progression and their potential value as biomarkers in solid tumors. It also highlights the biological characteristics of extracellular miRNAs that enable them to function as regulators of gene expression, such as biogenesis, gene silencing mechanisms, subcellular compartmentalization, and the functions and mechanisms of release.


2013 ◽  
Vol 114 (5) ◽  
pp. 602-610 ◽  
Author(s):  
Nico A. M. Schellart ◽  
Tjeerd P. van Rees Vellinga ◽  
Rob A. van Hulst

For over a century, studies on body fat (BF) in decompression sickness and venous gas embolism of divers have been inconsistent. A major problem is that age, BF, and maximal oxygen consumption (V̇o2max) show high multicollinearity. Using the Bühlmann model with eight parallel compartments, preceded by a blood compartment in series, nitrogen tensions and loads were calculated with a 40 min/3.1 bar (absolute) profile. Compared with Haldanian models, the new model showed a substantial delay in N2 uptake and (especially) release. One hour after surfacing, an increase of 14–28% in BF resulted in a whole body increase of the N2 load of 51%, but in only 15% in the blood compartment. This would result in an increase in the bubble grade of only 0.01 Kisman-Masurel (KM) units at the scale near KM = I−. This outcome was tested indirectly by a dry dive simulation (air breathing) with 53 male divers with a small range in age and V̇o2max to suppress multicollinearity. BF was determined with the four-skinfold method. Precordial Doppler bubble grades determined at 40, 80, 120, and 160 min after surfacing were used to calculate the Kisman Integrated Severity Score and were also transformed to the logarithm of the number of bubbles/cm2 (logB). The highest of the four scores yielded logB = −1.78, equivalent to KM = I−. All statistical outcomes of partial correlations with BF were nonsignificant. These results support the model outcomes. Although this and our previous study suggest that BF does not influence venous gas embolism (Schellart NAM, van Rees Vellinga TP, van Dijk FH, Sterk W. Aviat Space Environ Med 83: 951–957, 2012), more studies with different profiles under various conditions are needed to establish whether BF remains (together with age and V̇o2max) a basic physical characteristic or will become less important for the medical examination and for risk assessment.


2019 ◽  
Vol 47 (Suppl. 3) ◽  
pp. 51-53 ◽  
Author(s):  
Marcus Ewert Broman ◽  
Mikael Bodelsson

Background: Lipopolysaccharide (endotoxin) from the outer Gram-negative bacterial wall can induce a harmful immunologic response, involving hemodynamic deprivation, and is one important motor driving the septic cascade. The positively charged poly-imine ethylene layer on the oXiris membrane is capable of adsorbing negatively charged endotoxin molecules and removing them from the blood compartment. Endotoxin is detrimental and should be removed from blood. Summary: The adsorbable endotoxin fraction in blood arises from a tight balance between seeding from an infectious focus and removal by an overwhelmed immune system. The net sum of remaining endotoxin in blood is available for an adsorption process in the oXiris filter. Endotoxin data from 2 patients with severe Gram-negative septic shock and endotoxemia in this case series, speaks for a considerable share of the adsorption of the oXiris filter in the endotoxin net removal over time. Key Messages: Analysis of combined in vitro and in vivo data speaks for an effect of the oXiris filter in lowering endotoxin.


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