Background:
Circular RNAs (circRNAs) have been implicated in the pathogenesis of atherosclerosis (AS) and the migration and proliferation of vascular smooth muscle cells (VSMCs) under oxidized ...low-density lipoprotein (ox-LDL). Here, we defined the exact action of human circ_0007478 in VSMC migration and proliferation induced by ox-LDL.
Methods:
Human VSMCs (HVSMCs) were exposed to ox-LDL. Circ_0007478, microRNA (miR)-638, and rho-associated protein kinase 2 (ROCK2) levels were gauged by quantitative real-time PCR (qRT-PCR) and western blot. Cell viability and proliferation were assessed by MTT and EdU assays, respectively. Transwell assays were used to detect cell migration and invasion. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to evaluate the direct relationship between miR-638 and circ_0007478 or ROCK2.
Results:
Our data indicated that circ_0007478 expression was augmented in AS serum samples and ox-LDL-treated HVSMCs. Depletion of circ_0007478 attenuated HVSMC proliferation, migration, and invasion induced by ox-LDL. Mechanistically, circ_0007478 targeted miR-638 by directly pairing to miR-638. Reduction of miR-638 reversed the effects of circ_0007478 depletion on ox-LDL-evoked proliferation, migration, and invasion in HVSMCs. ROCK2 was a direct miR-638 target and miR-638-mediated inhibition of ROCK2 relieved ox-LDL-evoked HVSMC proliferation, migration, and invasion. Furthermore, circ_0007478 was identified as a competing endogenous RNA (ceRNA) for miR-638 to modulate ROCK2 expression.
Conclusion:
Our present study establishes an undescribed ceRNA regulatory network, in which circ_0007478 targets miR-638 to upregulate ROCK2, thereby contributing to ox-LDL-induced proliferation and migration in HVSMCs.
The role of HOX transcript antisense RNA (HOTAIR) has been proven to be important in tumorigenesis. However, how this molecule promotes metastasis and invasion in PCa is still unclear.
The ...relationship between HOTAIR and hepatocellular adhesion molecule (hepaCAM) in PCa was identified by immunohistochemistry, immunofluorescence, plasmid transfection, quantitative real-time PCR and immunoblotting. The regulatory effects of HOTAIR on hepaCAM and MAPK signalling and their key roles in PCa metastasis were investigated in vitro.
The expression of HOTAIR was inversely correlated with hepaCAM in the blood and tissue of PCa patients. Here, hepaCAM was identified as a novel target gene of HOTAIR and was critical for the invasiveness of PCa. HOTAIR recruited PRC2 to the hepaCAM promoter, resulting in high levels of H3K27me3 and the absence of hepaCAM with an abnormally activated MAPK pathway. Both HOTAIR depletion and EZH2 inhibition could induce hepaCAM re-expression with inhibitory MAPK signalling and decrease the invasive and metastatic capabilities of PCa cells.
This study demonstrates that HOTAIR promotes invasion and metastasis of PCa by decreasing the inhibitory effect of hepaCAM on MAPK signalling. Therefore, the HOTAIR/hepaCAM/MAPK axis may provide a new avenue towards therapeutic strategies and prognostic indicators for advanced prostate cancer.
Adenovirus (ADV) is a prevalent infective virus in children, accounting for around 5-10% of all cases of acute respiratory illnesses and 4-15% of pneumonia cases in children younger than five years ...old. Without treatment, severe ADV pneumonia could result in fatality rates of over 50% in cases of emerging strains or disseminated disease. This study aims to uncover the relationship of clinical indicators with primary ADV infection severity, regarding duration of hospitalization and liver injury.
In this retrospective study, we collected and analyzed the medical records of 1151 in-patients who met the inclusion and exclusion criteria. According to duration of hospitalization, all patients were divided into three groups. Then the difference and correlation of clinical indicators with ADV infection were analyzed, and the relationship among liver injury, immune cells and cytokines was evaluated.
The study revealed that patients with a duration of hospitalization exceeding 14 days had the highest percentage of abnormalities across most indicators. This was in contrast to the patients with a hospitalization duration of either less than or equal to 7 days or between 7 and 14 days. Furthermore, correlation analysis indicated that a longer duration of body temperature of ≥ 39°C, bilateral lung lobes infiltration detected by X ray, abnormal levels of AST, PaO2, and SPO2, and a lower age were all predictive of longer hospital stays. Furthermore, an elevated AST level and reduced liver synthesis capacity were related with a longer hospital stay and higher ADV copy number. Additionally, AST/ALT was correlated positively with IFN-γ level and IFN-γ level was only correlated positively with CD4
T cells.
The study provided a set of predicting indicators for longer duration of hospitalization, which responded for primary severe ADV infection, and elucidated the possible reason for prolonged duration of hospitalization attributing to liver injury via higher ADV copy number, IFN-γ and CD4
T cells, which suggested the importance of IFN-γ level and liver function monitoring for the patients with primary severe ADV infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The disc coupling has been widely used in aviation, ship and other fields, which often introduces the intermediate shaft to achieve large misalignment and ensure sufficient flexibility. However, ...there is no published and accurate theoretical dynamic model of this kind of coupling, and study to analyze the rotor system connected by the disc coupling with the intermediate shaft, especially with misalignment. Therefore, dynamic modeling and analysis of the rotor-bearing-disc coupling system with misalignment are carried out in this paper, and the dynamic model of the disc coupling with the intermediate shaft is established, emphatically. For the shafting connected by this kind of coupling, shaft misalignment can be unified as the combination of the angular misalignment between the drive shaft and the intermediate shaft, which simplifies the analysis of misalignment of the system with this kind of coupling. The accuracy of the established dynamic model is verified by the comparison of the critical speed between the finite element software and the dynamic model. The dynamic characteristics analysis reveals that: misalignment leads to the irregularity of the axis trajectory, the phenomenon of 1/4, 1/3, 1/2 subharmonic resonance, and the occurrence of the high-order harmonic components in the frequency-domain response, which can be used as the identification signal of misalignment. And it is effective to monitor the axis trajectory of the intermediate shaft for the rotor system connected by this kind of coupling.
MicroRNAs (miRNAs) play critical roles in the development of vascular diseases. However, the effects of miR-130a-5p and its functional targets on atherosclerosis (AS) are still largely unknown. In ...this regard, our aim is to explore the potentially important role of miR-130a-5p and its target gene during the progression of endothelial cell injury. We first found oxidized low-density lipoprotein (ox-LDL) induced FAS and cell apoptosis in HUVECs. Subsequently, miR-130a-5p expression was verified to be downregulated after ox-LDL treatment and negatively correlated with FAS, and FAS was identified as substantially upregulated in the ox-LDL-treated HUVEC cells. After that, the knockdown of FAS and overexpression of miR-130a-5p together were observed to aggregate ox-LDL-induced reduction of cell viability and apoptosis, cell cycle progression, cell proliferation, cell migration and invasion. In conclusion, we detected that miR-130a-5p contributed to the progression of endothelial cell injury by regulating of FAS, which may provide a new and promising therapeutic target for AS.
Abstract Objectives The aim is to evaluate the effect of viral inactivation methods on the quality and quantity of compounds in dried blood spots (DBS). Methods Three effective and common ...inactivation methods were selected via the literature search, including: heating at 56 °C for 30 min, irradiation with UVC for 30 min, and surface wetting with 70 % ethanol. The concentration and clinical predicting significance of hormones, amino acids, and acylcarnitines from DBS were assessed, and the quality and quantity of extracted deoxyribonucleic acid (DNA) from DBS were evaluated. Results Compared to control, we found that there was no significant difference on hormones concentration in the DBS treated by heating at 56 °C for 30 min (thyroid stimulating hormone p=0.36, 17-hydroxyprogesterone p=0.52). And heating at 56 °C for 30 min had a minimal changed coefficient of variation on the concentration of amino acids and acylcarnitines. All three inactivation methods slightly changed the yield of DNA extraction, but did not affect the quality of the DNA. Importantly, the three inactivation methods wouldn’t change the clinical predicting significance of above-compounds mostly, especially heating at 56 °C for 30 min. Conclusions Considering the minimal effect on the quality and quantity of various compounds, the contaminated DBS could be pretreated by the three inactivation methods, as temporary emergency inactivation methods, especially heating at 56 °C for 30 min.
Inborn errors of metabolism (IEMs) are uncommon. Although some studies have explored the distribution and characteristics of IEMs in newborns, the impact of these disorders on hospitalized newborns ...remains unclear. In this study, we gathered data from 21,840 newborn patients admitted for various medical conditions at the Children’s Hospital of Chongqing Medical University from January 2017 and December 2022. Liquid chromatography-tandem mass spectrometry (LC-MS/MS), gas chromatography-mass spectrometry (GC-MS/MS), and genetic analysis were used to elucidate the disease spectrum, incidence rate, and genetic characteristics of IEMs in hospitalized newborns. The results revealed that the incidence of IEMs in hospitalized newborns was 1/377 (58/21,840), with a higher incidence in full-term infants (1/428) than in premature infants (1/3,120). Among the diagnosed genetic metabolic diseases, organic acid metabolism disorders (1/662), amino acid metabolism disorders (1/950), and fatty acid oxidation disorders (1/10,920) were the most prevalent. Methylmalonic acidemia (MMA), especially the isolated form, emerged as the most common IEM, while neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and ornithine transcarbamylase deficiency (OTCD) were prevalent in premature infants. Of the 58 confirmed cases of IEMs, 72 variants were identified, of which 31.94% (23/72) had not been reported previously. This study contributes to understanding the incidence and clinical features of IEMs in hospitalized newborns, offering more efficient strategies for screening and diagnosing these disorders.
Traditional methods for thalassemia screening are time-consuming and easily affected by cell hemolysis or hemoglobin degradation in stored blood samples. Tandem mass spectrometry (MS/MS) proved to be ...an effective technology for sickle cell disorders (SCD) screening. Here, we developed a novel MS/MS method for β-thalassemia screening from dried blood spots (DBS). Stable isotopic-labeled peptides were used as internal standards for quantification and calculation of the α:β-globin ratios. We used the α:β-globin ratio cutoffs to differentiate between normal individuals and patients with thalassemia. About 781 patients and 300 normal individuals were analyzed. The α:β-globin ratios showed significant difference between normal and β-thalassemia patients (P<0.01), particularly when the disease was homozygous or double heterozygous with another α- or β-thalassemia mutation. In the parallel study, all cases screened for suspected thalassemia from six hundred DBS samples by using this MS/MS method were successfully confirmed by genotyping. The intra-assay and inter-assay CVs of the ratios ranged from 2.4% to 3.9% and 4.7% to 7.1%, and there was no significant sample carryover or matrix effect for this MS/MS method. Combined with SCD screening, this MS/MS method could be used as a first-line screening assay for both structural and expression abnormalities of human hemoglobin.
Traditional methods for thalassemia screening were depending on the structural integrity of tetramers and could be affected by hemolysis and degradation of whole blood samples, especially when stored. We used proteospecific peptides produced by the tryptic digestion of each globin to evaluate the production ratio between α- and β-globin chains, which turned out to be quite stable even when stored for more than two months. Though most of the peptides were specific to α-globin or β-globin, we only chose four most informative peptides and its stable isotopic-labeled peptides as internal standards for analysis, which could obtain a high accuracy. Currently, we are the first to address the application of MS/MS for thalassemia screening, when combined with SCD screening, this MS/MS method could be used as a first-line screening assay for both structural and expression abnormalities of human hemoglobin.
Display omitted
•A novel MS/MS approach used for first-line screening of β-thalassemia.•MS/MS can be applied to screen both structural and expression abnormalities of human hemoglobin.•Dried blood spots based β- thalassemia screening turn out to be convenient and efficient.•Quantitative analysis of Hb and the α:β peptide ratios can improve the screening for both α- and β-thalassemia.
The Shapley value is a well-known solution concept for TU games. The Maschler–Owen value and the NTU Shapley value are two well-known extensions of the Shapley value to NTU games. A hyperplane game ...is an NTU game in which the feasible set for each coalition is a hyperplane. On the domain of monotonic hyperplane games, the Maschler–Owen value is axiomatized (Hart Essays in game theory. Springer,
1994
). Although the domain of hyperplane game is a very interesting class of games to study, unfortunately, on this domain, the NTU Shapley value is not well-defined, namely, it assigns an empty set to some hyperplane games. A prize game (Hart Essays in game theory. Springer,
1994
) is an NTU game that can be obtained by “truncating” a hyperplane game. As such, a prize game describes essentially the same situation as the corresponding hyperplane game. It turns out that, on the domain of monotonic prize games, the NTU Shapley value is well-defined. Thus, one can define a value which is well-defined on the domain of monotonic hyperplane games as follows: given a monotonic hyperplane game, first, transform it into a prize game, and then apply the NTU Shapley value to it. We refer to the resulting value as the “generalized Shapley value” and compare the axiomatic properties of it with those of the Maschler–Owen value on the union of the class of monotonic hyperplane games and that of monotonic prize games. We also provide axiomatizations of the Maschler–Owen value and the generalized Shapley value on that domain.
PDF
