Acute myocardial infarction (AMI) is an ischemic heart disease with high mortality. AMI-induced hypoxia will trigger serious myocardial injury, such as cardiomyocyte apoptosis. miRNAs have been ...reported to be involved in the development of AMI. Our previous study revealed that hypoxia regulates the miRNAome of rat cardiomyoblast cells (H9c2), including many known “hypoxamiRs.” This study aimed to investigate the potential function of miR-361-3p in the hypoxic response of cardiomyocytes. H9c2 cells were cultured in hypoxic condition and rat AMI model was established by ligating the coronary artery. Cell apoptosis and miR-361-3p expression were measured in hypoxia-exposed H9c2 cell and myocardium of AMI rat. Gain- and loss-of-function analyses in vitro were performed to assess the effect of miR-361-3p in hypoxia-induced cardiomyocyte injury. Hypoxia induced notable changes in cell morphology, triggered cell apoptosis, increased cell membrane damage, and meanwhile decreased miR-361-3p expression in a time-dependent manner. AMI induced cell apoptosis in rat myocardium accompanied by downregulation of miR-361-3p. miR-361-3p overexpression markedly reduced hypoxia-induced cardiomyocyte injury; however, its downregulation had an opposite effect. Functionally, miR-361-3p mitigated hypoxia injury by inhibiting apoptosis via targeting apoptosis initiators
caspase-2/-8/-9
. This study revealed that miR-361-3p has a cardioprotective effect on hypoxia-induced cardiomyocyte injury, suggesting it may be a novel therapeutic target for hypoxia-related cardiac diseases.
Guanidinoacetic acid (GAA), an amino acid derivative that is endogenous to animal tissues including muscle and nerve, has been reported to enhance muscular performance. MicroRNA (miRNA) is a ...post-transcriptional regulator that plays a key role in nutrient-mediated myogenesis. However, the effects of GAA on myogenic differentiation and skeletal muscle growth, and the potential regulatory mechanisms of miRNA in these processes have not been elucidated. In this study, we investigated the effects of GAA on proliferation, differentiation, and growth in C2C12 cells and mice. The results showed that GAA markedly inhibited the proliferation of myoblasts, along with the down-regulation of cyclin D1 (
) and cyclin dependent kinase 4 (
) mRNA expression, and the upregulation of cyclin dependent kinase inhibitor 1A (
) mRNA expression. We also demonstrated that GAA treatment stimulated myogenic differentiation 1 (
) and myogenin (
) mRNA expression, resulting in an increase in the myotube fusion rate. Meanwhile, GAA supplementation promoted myotube growth through increase in total myosin heavy chain (MyHC) protein level, myotubes thickness and gastrocnemius muscle cross-sectional area. Furthermore, small RNA sequencing revealed that a total of eight miRNAs, including miR-133a-3p and miR-1a-3p cluster, showed differential expression after GAA supplementation. To further study the function of miR-133a-3p and miR-1a-3p in GAA-induced skeletal muscle growth, we transfected miR-133a-3p and miR-1a-3p mimics into myotube, which also induced muscle growth. Through bioinformatics and a dual-luciferase reporter system, the target genes of miR-133a-3p and miR-1a-3p were determined. These two miRNAs were shown to modulate the Akt/mTOR/S6K signaling pathway by restraining target gene expression. Taken together, these findings suggest that GAA supplementation can promote myoblast differentiation and skeletal muscle growth through miR-133a-3p- and miR-1a-3p-induced activation of the AKT/mTOR/S6K signaling pathway.
This study investigates the effect of aluminum (Al) on the microstructure, micro-hardness, and wettability of environmentally friendly Sn-20Bi-xAl (x = 0, 0.1, 0.3, 0.5 (wt.%)) solder alloys. ...Scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS) analysis, and X-ray diffraction (XRD), were used to identify the microstructure morphology and composition. The spreading area and contact angle of the Sn-20Bi-xAl alloys on Cu substrates were used to measure the wettability of solder alloys. The results indicate that Al increased the hardness to a maximum value of ~27.1 HV for x = 0.5. When the content of Al was more than 0.3 wt.%, the hardness change value gradually flattened. From the spreading test results, Al reduced the wettability of solder alloys. When the content of Al was 0.1 wt.%, the change was slight. When more than 0.3 wt.%, the wettability of Sn-20Bi-xAl solder alloys sharply dropped. The corrosion resistance of Sn-20Bi-0.1Al alloy was the best, and the corrosion rate was at the lowest value at 0.092 mm/a due to the dense corrosion products.
Background: Angiogenesis is essential for various physiological and pathological processes, such as embryonic development and cancer cell proliferation, migration, and invasion. Long noncoding RNAs ...(lncRNAs) play pivotal roles in normal homeostasis and disease processes by regulating gene expression through various mechanisms, including competing endogenous RNAs (ceRNAs) of target microRNAs (miRNAs). The lncRNA MYU is known to promote prostate cancer proliferation via the miR-184/c-Myc regulatory axis and to be upregulated in vascular endothelial cells under hypoxic conditions, which often occurs in solid tumors. In the present study, we investigated whether MYU might affect cancer growth by regulating angiogenesis in vascular endothelial cells under hypoxia. Methods: The expression of MYU-regulated miR-23a-3p and interleukin-8 (IL-8) in HUVEC cell lines was examined using qRT-PCR. The CCK-8 assay, EdU assay, wound-healing assay, and tube-formation assay were used to assess the effects of MYU on cell proliferation, migration, and tube formation of HUVEC cells in vitro. The dual-luciferase reporter assay was performed to examine the effects of miR-23a-3p on MYU and IL-8 expression. Results: We found that the overexpression of MYU and knockdown of miR-23a-3p in human umbilical vein endothelial cells (HUVECs) under hypoxia promoted cell proliferation, migration, and tube formation. Mechanistically, MYU was shown to bind competitively to miR-23a-3p, thereby preventing miR-23a-3p binding to the 3′ untranslated region of IL-8 mRNA. In turn, increased production of pro-angiogenic IL-8 promoted HUVEC proliferation, migration, and tube formation under hypoxia. Conclusion: This study identified a new role for lncRNA MYU as a ceRNA for miR-23a-3p and uncovered a novel MYU–miR-23a-3p–IL-8 regulatory axis for angiogenesis. MYU and/or miR-23a-3p may thus represent new targets for the treatment of hypoxia-related diseases by promoting angiogenesis.
Local hypoxia has recently been reported to occur in the white adipose tissue (WAT) microenvironment during obesity. Adipocytes have a unique life cycle that reflects the different stages of ...adipogenesis in the WAT niche. Long non-coding RNAs (lncRNAs) play an important role in the cellular response to hypoxia. However, the differentially hypoxic responses of preadipocytes during adipogenesis and the potential role of lncRNAs in this process remain to be elucidated. Here, we evaluated the differentially hypoxic responses of primary hamster preadipocytes during adipogenesis and analyzed mRNA and lncRNA expression in same Ribo-Zero RNA-seq libraries. Hypoxia induced HIF-1α protein during adipogenesis and caused divergent changes of cell phenotypes. A total of 10,318 mRNAs were identified to be expressed in twenty libraries (five timepoints), and 3,198 differentially expressed mRNAs (DE mRNAs) were detected at five timepoints (hypoxia vs. normoxia). Functional enrichment analysis revealed the shared and specific hypoxia response pathways in the different stages of adipogenesis. Hypoxia differentially modulated the expression profile of adipose-associated genes, including adipokines, lipogenesis, lipolysis, hyperplasia, hypertrophy, inflammatory, and extracellular matrix. We also identified 4,296 lncRNAs that were expressed substantially and detected 1,431 DE lncRNAs at five timepoints. Two, 3, 5, 13, and 50 DE mRNAs at D0, D1, D3, D7, and D11, respectively, were highly correlated and locus-nearby DE lncRNAs and mainly involved in the cell cycle, vesicle-mediated transport, and mitochondrion organization. We identified 28 one-to-one lncRNA-mRNA pairs that might be closely related to adipocyte functions, such as
ENSCGRT00015041780
-
Hilpda
,
TU2105
-
Cdsn
, and
TU17588
-
Ltbp3
. These lncRNAs may represent the crucial regulation axis in the cellular response to hypoxia during adipogenesis. This study dissected the effects of hypoxia in the cell during adipogenesis, uncovered novel regulators potentially associated with WAT function, and may provide a new viewpoint for interpretation and treatment of obesity.
Skeletal muscle formation is an extremely important step in animal growth and development. Recent studies have found that TMEM8c (also known as Myomaker, MYMK), a muscle-specific transmembrane ...protein, can promote myoblast fusion and plays a key role in the normal development of skeletal muscle. However, the effect of Myomaker on porcine (
) myoblast fusion and the underlying regulatory mechanisms remain largely unknown. Therefore, in this study, we focused on the role and corresponding regulatory mechanism of the
gene during skeletal muscle development, cell differentiation, and muscle injury repair in pigs. We obtained the entire 3' UTR sequence of porcine
using the 3' RACE approach and found that miR-205 inhibited porcine myoblast fusion by targeting the 3' UTR of
. In addition, based on a constructed porcine acute muscle injury model, we discovered that both the mRNA and protein expression of
were activated in the injured muscle, while miR-205 expression was significantly inhibited during skeletal muscle regeneration. The negative regulatory relationship between miR-205 and Myomaker was further confirmed in vivo. Taken together, the present study reveals that Myomaker plays a role during porcine myoblast fusion and skeletal muscle regeneration and demonstrates that miR-205 inhibits myoblast fusion through targeted regulation of the expression of Myomaker.
CeO2 with X-architecture was synthesized using the hydrothermal route assisted by polyvinyl pyrrolidone, and employed to investigate the degradation of methylene blue under UV-light irradiation. The ...as-obtained CeO2 sample exhibited higher photocatalytic activity than traditional CeO2 sample prepared by precipitation route due to its irregular X-architecture shape with clear boundary and micro/mesopore surface structure. The novel X-architecture shape of CeO2 facilitates the efficient photo-generated charge transfer and separation under UV-light irradiation, leading to the superior stability for the photo-degradation of methylene blue.
•CeO2 with X-architecture was synthesized by hydrothermal route.•CeO2 with X-architecture presented high photodegradation for methylene blue.•CeO2 with X-architecture showed superior stability under UV–visible region.•X-architecture facilitates photo-generated charge transfer and separation.
CeO2 with X-architecture was synthesized using the hydrothermal route assisted by polyvinyl pyrrolidone, and employed to investigate the degradation of methylene blue under UV-light irradiation. The ...as-obtained CeO2 sample exhibited higher photocatalytic activity than traditional CeO2 sample prepared by precipitation route due to its irregular X-architecture shape with clear boundary and micro/mesopore surface structure. The novel X-architecture shape of CeO2 facilitates the efficient photo-generated charge transfer and separation under UV-light irradiation, leading to the superior stability for the photo-degradation of methylene blue.
Inexpensive tool condition (TC) monitoring plays a significant role for less human duty machining process in large-scale manufactory. A time-sequential spindle current-based tool breakage diagnosis ...technique with least squares support vector machine (LS-SVM) classifier is investigated to provide an inexpensive on-line TC monitoring system for milling process. The recognition technique consists of a spindle motor current feedback sensor, a signal processor, and an intelligent classifier. The processor generates machining condition features with Sym6 wavelet transformation to decompose the feedback signals in time domains to generate sequence samples. The features involving both normal and broken tool conditions during machining are fed into the classifier to conduct kernel-based LS-SVM training. With the transformation and training, an object oriented representation function as the LS-SVM classifier is set up and then utilized to diagnose tool fractures in the real time under varying cutting conditions. Experiments were conducted on a milling platform with the built monitoring system consisting of a current acquisition system and its processing software. Experimental results show high accuracy rate and high calculation performance in on-line monitoring of cutting tool conditions for milling process.
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