Acute myocardial infarction (AMI) represents the acute manifestation of coronary artery disease. In recent years, microRNAs (miRNAs) have been extensively studied in AMI. This study focused on the role of miR-431-5p in AMI and its effect on cardiomyocyte apoptosis after AMI. The expression of miR-431-5p was analyzed by quantitative real-time PCR (qRT-PCR). By interfering with miR-431-5p in hypoxia-reoxygenation (H/R)-induced HL-1 cardiomyocytes, the effect of miR-431-5p on cardiomyocyte apoptosis after AMI was examined. The interaction between miR-431-5p and selenoprotein T (SELT) mRNA was verified by dual-luciferase reporter assay. Cell apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and flow cytometry. Cell viability was examined by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay. The results of qRT-PCR showed that the expression of miR-431-5p in AMI myocardial tissues and H/R-induced HL-1 cardiomyocytes was significantly increased. After interfering with miR-431-5p, the expression of SELT in HL-1 cells was up-regulated, cell apoptosis was decreased, cell viability was increased, and lactate dehydrogenase (LDH) activity was decreased. The dual-luciferase reporter assay confirmed the targeting relationship between miR-431-5p and SELT1 3' untranslated region (UTR). In H/R-induced HL-1 cells, the simultaneous silencing of SELT and miR-431-5p resulted in a decrease of Bcl-2 expression, an increase of Bax expression, and an increase of cleaved-caspase 3 expression compared with silencing miR-431-5p alone. Also, cell viability was decreased, while LDH activity was increased by the simultaneous silencing of SELT and miR-431-5p. Interfering miR-431-5p protected cardiomyocytes from AMI injury via restoring the expression of SELT, providing new ideas for the treatment of AMI.
- MeSH
- apoptóza * genetika MeSH
- infarkt myokardu * genetika metabolismus MeSH
- kardiomyocyty metabolismus MeSH
- lidé MeSH
- mikro RNA genetika metabolismus MeSH
- myši MeSH
- reperfuzní poškození myokardu * metabolismus MeSH
- selenoproteiny genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- mikro RNA MeSH
- MIRN431 microRNA, human MeSH Prohlížeč
- MIRN431 microRNA, mouse MeSH Prohlížeč
- selenoprotein T, mouse MeSH Prohlížeč
- selenoproteiny MeSH
A joint determination of the reactor antineutrino spectra resulting from the fission of ^{235}U and ^{239}Pu has been carried out by the Daya Bay and PROSPECT Collaborations. This Letter reports the level of consistency of ^{235}U spectrum measurements from the two experiments and presents new results from a joint analysis of both data sets. The measurements are found to be consistent. The combined analysis reduces the degeneracy between the dominant ^{235}U and ^{239}Pu isotopes and improves the uncertainty of the ^{235}U spectral shape to about 3%. The ^{235}U and ^{239}Pu antineutrino energy spectra are unfolded from the jointly deconvolved reactor spectra using the Wiener-SVD unfolding method, providing a data-based reference for other reactor antineutrino experiments and other applications. This is the first measurement of the ^{235}U and ^{239}Pu spectra based on the combination of experiments at low- and highly enriched uranium reactors.
- Publikační typ
- časopisecké články MeSH
Various surgical treatments for osteoarthritis (OA) secondary to hip dysplasia have been reported in the literature. According to the position of the arthroplasty cup, generally they could be divided into two groups: the primary rotational center (PRC) group and the high hip center (HHC) group. Some surgeons prefer the HHC technique. Without doubt it is less demanding, but several concerns exist against the long-term stability. When restoring the PRC, since the dysplastic acetabulum is usually shallower and underdeveloped, bone grafts or other biosynthetic materials are usually needed for the ideal fixation. The source of grafts is quite wide. For example, they could be autologous (femoral head, iliac crest) or homologous (allografts), bulky or morselized. Medial wall protrusion technique, as well as other materials like oblong cup, porous titanium and tantalum augments, 3D printed implants could also be an option. Except these, reports are also divided into cemented and cementless techniques. Therefore, no technique is perfect and clinical results so far are quite variable. We think it's necessary to compare the pros and cons between each other. Key words:hip dysplasia, total hip replacement, cup position, secondary osteoarthritis.
Bidirectional interactions between astrocytes and neurons have physiological roles in the central nervous system and an altered state or dysfunction of such interactions may be associated with neurodegenerative diseases, such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Astrocytes exert structural, metabolic and functional effects on neurons, which can be either neurotoxic or neuroprotective. Their neurotoxic effect is mediated via the senescence-associated secretory phenotype (SASP) involving pro-inflammatory cytokines (e.g., IL-6), while their neuroprotective effect is attributed to neurotrophic growth factors (e.g., NGF). We here demonstrate that the p53 isoforms Δ133p53 and p53β are expressed in astrocytes and regulate their toxic and protective effects on neurons. Primary human astrocytes undergoing cellular senescence upon serial passaging in vitro showed diminished expression of Δ133p53 and increased p53β, which were attributed to the autophagic degradation and the SRSF3-mediated alternative RNA splicing, respectively. Early-passage astrocytes with Δ133p53 knockdown or p53β overexpression were induced to show SASP and to exert neurotoxicity in co-culture with neurons. Restored expression of Δ133p53 in near-senescent, otherwise neurotoxic astrocytes conferred them with neuroprotective activity through repression of SASP and induction of neurotrophic growth factors. Brain tissues from AD and ALS patients possessed increased numbers of senescent astrocytes and, like senescent astrocytes in vitro, showed decreased Δ133p53 and increased p53β expression, supporting that our in vitro findings recapitulate in vivo pathology of these neurodegenerative diseases. Our finding that Δ133p53 enhances the neuroprotective function of aged and senescent astrocytes suggests that the p53 isoforms and their regulatory mechanisms are potential targets for therapeutic intervention in neurodegenerative diseases.
- MeSH
- alternativní sestřih MeSH
- Alzheimerova nemoc metabolismus patologie MeSH
- amyotrofická laterální skleróza metabolismus patologie MeSH
- astrocyty cytologie účinky léků metabolismus MeSH
- autofagie účinky léků MeSH
- genetické vektory genetika metabolismus MeSH
- interleukin-6 genetika metabolismus MeSH
- kokultivační techniky MeSH
- kultivované buňky MeSH
- leupeptiny farmakologie MeSH
- lidé MeSH
- malá interferující RNA metabolismus MeSH
- mozek metabolismus patologie MeSH
- nádorový supresorový protein p53 antagonisté a inhibitory genetika metabolismus MeSH
- neurony cytologie metabolismus MeSH
- neuroprotekce fyziologie MeSH
- protein - isoformy antagonisté a inhibitory genetika metabolismus MeSH
- RNA interference MeSH
- sekvestosom 1 antagonisté a inhibitory genetika metabolismus MeSH
- serin-arginin sestřihové faktory antagonisté a inhibitory genetika metabolismus MeSH
- stárnutí buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- benzyloxycarbonylleucyl-leucyl-leucine aldehyde MeSH Prohlížeč
- interleukin-6 MeSH
- leupeptiny MeSH
- malá interferující RNA MeSH
- nádorový supresorový protein p53 MeSH
- protein - isoformy MeSH
- sekvestosom 1 MeSH
- serin-arginin sestřihové faktory MeSH
- SQSTM1 protein, human MeSH Prohlížeč
- SRSF3 protein, human MeSH Prohlížeč
