Osteoporosis is characterized by low bone mass and damage to the bone tissue’s microarchitecture, leading to increased fracture risk. Several studies have provided evidence for associations between ...psychosocial stress and osteoporosis through various pathways, including the hypothalamic-pituitary-adrenocortical axis, the sympathetic nervous system, and other endocrine factors. As psychosocial stress provokes oxidative cellular stress with consequences for mitochondrial function and cell signaling (e.g., gene expression, inflammation), it is of interest whether extracellular vesicles (EVs) may be a relevant biomarker in this context or act by transporting substances. EVs are intercellular communicators, transfer substances encapsulated in them, modify the phenotype and function of target cells, mediate cell-cell communication, and, therefore, have critical applications in disease progression and clinical diagnosis and therapy. This review summarizes the characteristics of EVs, their role in stress and osteoporosis, and their benefit as biological markers. We demonstrate that EVs are potential mediators of psychosocial stress and osteoporosis and may be beneficial in innovative research settings.
Rak gruczołu krokowego (PCa) jest najczęstszym rodzajem nowotworu wśród mężczyzn w Europie i dotyczy to niemal całego świata. Zalecenia dotyczące badań przesiewowych oraz rozpoznania opierają się na ...pomiarach antygenu swoistego prostaty (PSA) i badaniu gruczołu krokowego palcem przez odbytnicę (DRE). Obie metody diagnostyczne najczęściej wskazują na konieczność wykonania biopsji prostaty. Ograniczona specyfika testu PSA powoduje jednak potrzebę opracowania nowych i lepszych narzędzi diagnostycznych. W ciągu ostatnich kilku lat, nowe podejście diagnostyczne, zapewniają biomarkery molekularne, które jako alternatywa PSA, zostały wprowadzone do użytku klinicznego. Nowoczesne biomarkery umożliwiają wykorzystywanie ich nie tylko jako nieinwazyjne narzędzia diagnostyczne, ale także zapewniają śledzenie zmian na każdym etapie choroby oraz ocenę agresywności guza i monitorowanie procesu terapeutycznego. Najbardziej obiecującą grupą są markery molekularne, wśród których dużą nadzieję wiąże się z wykorzystaniem pozakomórkowych cząstek mikroRNA (miRNA, miR). miRNA tworzą klasę małych o długości około 22 nukleotydów, niekodujących cząsteczek RNA, które biorą udział w potranskrypcyjnej regulacji ekspresji licznych genów. W artykule przedstawiono aktualną wiedzę dotyczącą roli miRNA w PCa, w tym dane dotyczące szlaku sygnałowego receptora androgenowego (AR signaling), cyklu komórkowego, procesu przejścia nabłonkowo-mezenchymalnego (EMT), rakowych komórek macierzystych (CSC), a nawet rolę miRNA jako narzędzia terapeutycznego PCa. Znalezienie lepszych biomarkerów PCa, na bazie miRNA, zastępujących obecny pomiar PSA, jest bardzo potrzebne w nowoczesnej praktyce onkologicznej.
Die komplementäre Bindung an eine miRNA‐Sequenz in lebenden Zellen führt zur Bildung chiraler selbstorganisierter plasmonischer Nanostäbchendimere mit spezifischem plasmonischem Zirkulardichroismus, ...oberflächenverstärkter Raman‐Streuung (SERS) und Fluoreszenz. Wie H. Kuang, L. M. Liz‐Marzán et al. in ihrer Zuschrift auf S. 10704 beschreiben, gelingen mit dieser Methode die In‐situ‐Bildgebung sowie der hoch empfindliche und selektive Nachweis von miRNA. Mit dem Ansatz lassen sich zudem Wechselwirkungen, Bewegungen und Kinetiken von Biomolekülen in lebenden Zellen verfolgen.
MicroRNAs (miRNAs) may contribute to the development of depression and its treatment. Here, we used the hypothesis-neutral approach of next-generation sequencing (NGS) to gain comprehensive ...understanding of the effects of a course of electroconvulsive stimulation (ECS), the animal model equivalent of electroconvulsive therapy (ECT), on rat hippocampal miRNAs. Significant differential expression (
p
< 0.001) of six hippocampal miRNAs was noted following NGS, after correcting for multiple comparisons. Three of these miRNAs were upregulated (miR-132, miR-212, miR-331) and three downregulated (miR-204, miR-483, miR-301a). qRT-PCR confirmed significant changes in four of the six miRNAs (miR-132, miR-212, miR-204, miR-483). miR-483 was also significantly reduced in frontal cortex, though no other significant alterations were noted in frontal cortex, cerebellum, or whole blood. Assessing the translatability of the results, miR-132 and miR-483 were significantly reduced in whole blood samples from medicated patients with depression (
n
= 50) compared to healthy controls (
n
= 45), though ECT had no impact on miRNA levels. Notably, pre-ECT miR-204 levels moderately positively correlated with depression severity at baseline and moderately negatively correlated with mood score reduction post-ECT. miRNAs were also examined in cerebrospinal fluid and serum from a separate cohort of patients (
n
= 8) treated with ECT; no significant changes were noted post-treatment. However, there was a large positive correlation between changes in miR-212 and mood score post-ECT in serum. Though replication studies using larger sample sizes are required, alterations in miRNA expression may be informative about the mechanism of action of ECS/ECT and in turn might give insight into the neurobiology of depression.
Abgeliefert: Ein System aus festen Lipidnanopartikeln (SLNs) wurde für den Transport von MicroRNA‐34a (miR‐34a; interessant für die Therapie von Krebsstammzellen (CSCs)) in Lungengewebe entwickelt. ...In SLNs mit miR‐34a (miSLNs‐34a) ist die MicroRNA vor dem Abbau im Serum geschützt, und ihre zelluläre In‐vitro‐Transfektionseffizienz ist erhöht. Die Behandlung mit miSLNs‐34a führt daher zu einer erhöhten Überlebenswahrscheinlichkeit von mit CSCs infizierten Mäusen (siehe Bild).
DNAzymes have been recognized as promising transducing agents for visualizing endogenous biomarkers, but their inefficient intracellular delivery and limited amplification capacity (including ...insufficient cofactor supply) preclude their extensive biological application. Herein, an autocatalytic DNAzyme (ACD) biocircuit is constructed for amplified microRNA imaging in vivo based on a hybridization chain reaction (HCR) and DNAzyme biocatalysis, sustained by a honeycomb MnO2 nanosponge (hMNS). The hMNS not only delivers DNA probes, but also supplies Mn2+ as a DNAzyme cofactor and magnetic resonance imaging (MRI) agent. Through the subsequent cross‐activation of HCR and DNAzyme amplicons, the ACD amplifies the limited signal resulting from miRNA recognition. The hMNS/ACD system was used to image microRNA in vivo, thus demonstrating its great promise in cancer diagnosis.
Ein autokatalytischer Kreislauf für die in‐vivo‐Fluoreszenz/Molekülresonanz‐Bildgebung wird auf Grundlage einer Hybridisierungskettenreaktion (HCR) und DNAzym‐Biokatalyse konstruiert und durch einen MnO2‐Nanoschwamm (hMNS) unterstützt. hMNS wurde dabei zur Bereitstellung der DNA und zur Versorgung des DNAzym mit Mn2+ als Kofaktor genutzt. Dieses System wurde zum Nachweis von mikroRNA in vivo verwendet und zeigt ein großes Potential in der Krebsdiagnose.
Abstract
Background
In this study, the objective was to evaluate the diagnostic performance of some miRNAs, which were shown to have a diagnostic value for prostate cancer (PCa), and the effect of ...chronic prostatitis in distinguishing benign prostatic hyperplasia (BPH) and PCa.
Materials and methods
Serum levels of 11 miRNAs were investigated in BPH, chronic prostatitis and PCa patients. Measurements were performed using qRT-PCR.
Results
In the analysis, serum levels of miR-375, -125b-5p, -30c-5p, -26b-5p, and let-7c-5p were downregulated in cancer compared with non-cancer group and AUCs of these miRNAs in distinguishing PCa group from non-cancer group were calculated as 0.781, 0.782, 0.762, 0.874, and 0.845, respectively. AUC of the combination of miR-375 and miR-26b-5p in distinguishing PCa group from non-cancer group was 0.891, AUC of these two miRNAs in distinguishing PCa group from BPH group was 0.944.
Conclusion
In our study, 11 miRNAs were studied and 5 of these miRNAs were considered as biomarker candidates as these miRNAs, individually or combined, could be used to distinguish PCa from benign conditions. Furthermore, a higher specificity and sensitivity were obtained in distinguishing BPH and PCa when data for diagnostic potential of miRNAs were analyzed without including chronic prostatic group.
Eine chemische Methode für die nachsynthetische Markierung von Prä‐MikroRNAs (Prä‐miRNAs) auf festem Träger mit einfach zugänglichen Reagentien wird beschrieben. Die Methode wurde genutzt, um eine ...Bibliothek von 31 Prä‐MikroRNAs mit gebräuchlichen Markierungen, einschließlich Cy3, Trioxalen, Biotin und BHQ‐1, herzustellen.
Exosomal microRNAs (miRNAs) are important biomarkers for clinical diagnosis and disease treatment monitoring. However, most approaches for exosomal miRNA detection are time‐consuming, laborious, and ...expensive. Herein, we report a virus‐mimicking fusogenic vesicle (Vir‐FV) that enables rapid, efficient, and high‐throughput detection of exosomal miRNAs within 2 h. Fusogenic proteins on Vir‐FVs can specifically target the sialic‐acid‐containing receptors on exosomes, inducing efficient fusion of Vir‐FVs and exosomes. Upon vesicle content mixing, the molecular beacons encapsulated in Vir‐FVs specifically hybridize with the target miRNAs in the exosomes, generating fluorescence. Combined with flow cytometry, the Vir‐FVs can not only detect exosomal miRNAs but also distinguish tumor exosomes from normal exosomes by sensing the tumor‐related miRNAs, paving the way towards the rapid and efficient detection of exosomal miRNAs for diagnosis and prognosis prediction of diseases.
Ein Virus‐imitierendes fusogenes Vesikel (Vir‐FV) wurde für die schnelle In‐situ‐Detektion exosomaler miRNA entwickelt. Vir‐FVs zielen auf die Sialsäure‐Rezeptoren an Exosomen ab, was die effiziente Fusion zwischen den Vir‐FVs und den Exosomen auslöst. In Vir‐FVs eingekapselte „Molecular Beacons” können spezifisch exosomale Ziel‐miRNA detektieren, was den Einsatz in der Krebsdiagnose und Therapieüberwachung ermöglicht.
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