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1.
Front Endocrinol (Lausanne) ; 15: 1346284, 2024.
Article in English | MEDLINE | ID: mdl-38628585

ABSTRACT

Objective: This study aims to analyze the association between the occurrence of thyroid nodules and various factors and to establish a risk factor model for thyroid nodules. Methods: The study population was divided into two groups: a group with thyroid nodules and a group without thyroid nodules. Regression with the least absolute shrinkage and selection operator (Lasso) was applied to the complete dataset for variable selection. Binary logistic regression was used to analyze the relationship between various influencing factors and the prevalence of thyroid nodules. Results: Based on the screening results of Lasso regression and the subsequent establishment of the Binary Logistic Regression Model on the training dataset, it was found that advanced age (OR=1.046, 95% CI: 1.033-1.060), females (OR = 1.709, 95% CI: 1.342-2.181), overweight individuals (OR = 1.546, 95% CI: 1.165-2.058), individuals with impaired fasting glucose (OR = 1.590, 95% CI: 1.193-2.122), and those with dyslipidemia (OR = 1.588, 95% CI: 1.197-2.112) were potential risk factors for thyroid nodule disease (p<0.05). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve for the Binary Logistic Regression Model is 0.68 (95% CI: 0.64-0.72). Conclusions: advanced age, females, overweight individuals, those with impaired fasting glucose, and individuals with dyslipidemia are potential risk factors for thyroid nodule disease.


Subject(s)
Dyslipidemias , Thyroid Nodule , Female , Humans , Thyroid Nodule/epidemiology , Thyroid Nodule/diagnosis , Logistic Models , Overweight/complications , Risk Factors , Glucose
2.
Front Pharmacol ; 15: 1337749, 2024.
Article in English | MEDLINE | ID: mdl-38666026

ABSTRACT

(R, S)- and (S)-ketamine have made significant progress in the treatment of treatment-resistant depression (TRD) and have become a research focus in recent years. However, they both have risks of psychomimetic effects, dissociative effects, and abuse liability, which limit their clinical use. Recent preclinical and clinical studies have shown that (R)-ketamine has a more efficient and lasting antidepressant effect with fewer side effects compared to (R, S)- and (S)-ketamine. However, a recent small-sample randomized controlled trial found that although (R)-ketamine has a lower incidence of adverse reactions in adult TRD treatment, its antidepressant efficacy is not superior to the placebo group, indicating its antidepressant advantage still needs further verification and clarification. Moreover, an increasing body of research suggests that (R)-ketamine might also have significant applications in the prevention and treatment of medical fields or diseases such as cognitive disorders, perioperative anesthesia, ischemic stroke, Parkinson's disease, multiple sclerosis, osteoporosis, substance use disorders, inflammatory diseases, COVID-19, and organophosphate poisoning. This article briefly reviews the mechanism of action and research on antidepressants related to (R)-ketamine, fully revealing its application potential and development prospects, and providing some references and assistance for subsequent expanded research.

3.
Opt Express ; 31(22): 36314-36326, 2023 Oct 23.
Article in English | MEDLINE | ID: mdl-38017786

ABSTRACT

The intensity coupling characteristics of Ne dual-isotope inflation and dual-longitudinal-mode operation ring lasers were investigated based on the Lamb theory. Considering the contribution of the Ne isotope system to the polarization of the gain medium and gain saturation effects, the frequency coupling effects were analyzed. Combined with the plasma dispersion function, the optical cavity length is 0.47 m, Ne20: Ne22= 0.53:0.47; the frequency spacing of the adjacent longitudinal mode is 640 MHz, and the intensity tuning curve of the ring laser is simulated. The alterations in the gain self-saturation and mutual saturation coefficients between the four frequencies generated via dual-longitudinal mode splitting are comprehensively discussed. Finally, a detection experiment for the intensity-tuning curve is designed to verify the theoretical analysis.

4.
Hortic Res ; 10(6): uhad086, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37786525

ABSTRACT

Walnut anthracnose induced by Colletotrichum gloeosporioides is a disastrous disease that severely restricts the development of the walnut industry in China. Long non-coding RNAs (lncRNAs) are involved in adaptive responses to disease, but their roles in the regulation of walnut anthracnose resistance response are not well defined. In this study, transcriptome analysis demonstrated that a C. gloeosporioides-induced lncRNA, lncRNA109897, located upstream from the target gene JrCCR4, upregulated the expression of JrCCR4. JrCCR4 interacted with JrTLP1b and promoted its transcriptional activity. In turn, JrTLP1b induced the transcription of lncRNA109897 to promote its expression. Meanwhile, transient expression in walnut leaves and stable transformation of Arabidopsis thaliana further proved that lncRNA, JrCCR4, and JrTLP1b improve the resistance of C. gloeosporioides. Collectively, these findings provide insights into the mechanism by which the lncRNA109897-JrCCR4-JrTLP1b transcriptional cascade regulates the resistance of walnut to anthracnose.

5.
Sensors (Basel) ; 23(6)2023 Mar 17.
Article in English | MEDLINE | ID: mdl-36991932

ABSTRACT

Frequency-difference-stabilized dual-frequency solid-state lasers with tunable and large frequency difference have become an ideal light source for the high-accuracy absolute-distance interferometric system due to their stable multistage synthetic wavelengths. In this work, the advances in research on oscillation principles and key technologies of the different kinds of dual-frequency solid-state lasers are reviewed, including birefringent dual-frequency solid-state lasers, biaxial and two-cavity dual-frequency solid-state lasers. The system composition, operating principle, and some main experimental results are briefly introduced. Several typical frequency-difference stabilizing systems for dual-frequency solid-state lasers are introduced and analyzed. The main development trends of research on dual-frequency solid-state lasers are predicted.

6.
Front Microbiol ; 14: 1137590, 2023.
Article in English | MEDLINE | ID: mdl-36998393

ABSTRACT

The intercropping of grass in orchards has beneficial effects on soil properties and soil microbial communities and is an important soil management measure for improving orchard productivity and land-use efficiency. However, few studies have explored the effects of grass intercropping on rhizosphere microorganisms in walnut orchards. In this study, we explored the microbial communities of clear tillage (CT), walnut/ryegrass (Lolium perenne L.) (Lp), and walnut/hairy vetch (Vicia villosa Roth.) (Vv) intercropping system using MiSeq sequencing and metagenomic sequencing. The results revealed that the composition and structure of the soil bacterial community changed significantly with walnut/Vv intercropping compared to CT and walnut/Lp intercropping. Moreover, the walnut/hairy vetch intercropping system had the most complex connections between bacterial taxa. In addition, we found that the soil microorganisms of walnut/Vv intercropping had a higher potential for nitrogen cycling and carbohydrate metabolism, which may be related to the functions of Burkholderia, Rhodopseudomonas, Pseudomonas, Agrobacterium, Paraburkholderia, and Flavobacterium. Overall, this study provided a theoretical basis for understanding the microbial communities associated with grass intercropping in walnut orchards, providing better guidance for the management of walnut orchards.

8.
Sensors (Basel) ; 22(16)2022 Aug 22.
Article in English | MEDLINE | ID: mdl-36016061

ABSTRACT

In order to stabilize the self-biasing state of a laser gyroscope, a dual-longitudinal-mode asymmetric frequency stabilization technique was studied. The special frequency stabilization is based on the accurate control of the intensity tuning curve in the prism ring laser. In this study, the effects of the ratio of the Ne isotopes, the inflation pressure, and the frequencies coupling on the intensity tuning curve in a laser gyro were examined. The profiles of the intensity tuning curve were simulated under the mixing ratios of Ne20 and Ne22 of 1:1 and 7:3, and the inflation pressures were 350 Pa, 400 Pa, and 450 Pa. The mixing ratio of Ne20 and Ne27 was dealt with similarly. The method for precisely adjusting the profiles of the intensity tuning curve was analyzed. The profiles were verified by experiments under different isotope ratios and pressures. Finally, based on a prism ring laser with an optical length of 0.47 m, the proposed frequency stabilization method was preliminarily verified.

9.
Molecules ; 27(14)2022 Jul 09.
Article in English | MEDLINE | ID: mdl-35889286

ABSTRACT

Poly(p-phenylene terephthalamide) (PPTA) is one kind of lyotropic liquid crystal polymer. Kevlar fibers performed from PPTA are widely used in many fields due to their superior mechanical properties resulting from their highly oriented macromolecular structure. However, the "infusible and insoluble" characteristic of PPTA gives rise to its poor processability, which limits its scope of application. The strong interactions and orientation characteristic of aromatic amide segments make PPTA attractive in the field of self-assembly. Chemical derivation has proved an effective way to modify the molecular structure of PPTA to improve its solubility and amphiphilicity, which resulted in different liquid crystal behaviors or supramolecular aggregates, but the modification of PPTA is usually complex and difficult. Alternatively, higher-order all-PPTA structures have also been realized through the controllable hierarchical self-assembly of PPTA from the polymerization process to the formation of macroscopic products. This review briefly summarizes the self-assembly methods of PPTA-based materials in recent years, and focuses on the polymerization-induced PPTA nanofibers which can be further fabricated into different macroscopic architectures when other self-assembly methods are combined. This monomer-started hierarchical self-assembly strategy evokes the feasible processing of PPTA, and enriches the diversity of product, which is expected to be expanded to other liquid crystal polymers.

10.
Plant J ; 111(4): 1152-1166, 2022 08.
Article in English | MEDLINE | ID: mdl-35765867

ABSTRACT

Walnut (Juglans regia L.) anthracnose, induced by Colletotrichum gloeosporioides, is a catastrophic disease impacting the walnut industry in China. Although WRKY transcription factors play a key role in plant immunity, the function of the WRKY gene family in walnut resistance to C. gloeosporioides is not clear. Here, through transcriptome sequencing and quantitative real-time polymerase chain reaction (qRT-PCR), we identified a differentially expressed gene, JrWRKY21, that was significantly upregulated upon C. gloeosporioides infection in walnut. JrWRKY21 positively regulated walnut resistance to C. gloeosporioides, as demonstrated by virus-induced gene silencing and transient gene overexpression. Additionally, JrWRKY21 directly interacted with the transcriptional activator of the pathogenesis-related (PR) gene JrPTI5L in vitro and in vivo, and could bind to the W-box in the JrPTI5L promoter for transcriptional activation. Moreover, JrPTI5L could induce the expression of the PR gene JrPR5L through binding to the GCCGAC motif in the promoter. Our data support that JrWRKY21 can indirectly activate the expression of the JrPR5L gene via the WRKY21-PTI5L protein complex to promote resistance against C. gloeosporioides in walnut. The results will enhance our understanding of the mechanism behind walnut disease resistance and facilitate the genetic improvement of walnut by molecular breeding for anthracnose-resistant varieties.


Subject(s)
Colletotrichum , Juglans , Colletotrichum/genetics , Disease Resistance/genetics , Juglans/genetics , Plant Diseases , Transcription Factors/genetics , Transcription Factors/metabolism
11.
Front Genet ; 13: 1086356, 2022.
Article in English | MEDLINE | ID: mdl-36685877

ABSTRACT

Background: Alfalfa (Medicago sativa L.), serves as a legume with high drought tolerance, is a major forage crop with a high biomass of production. However, the molecular mechanism of Alfalfa in response to drought stress are still unclear. Results: We constructed the first full-length transcriptome for Alfalfa root. 21.53Gb clean data were obtained by further data filtering, in which incorporate 566,076 reads of Insert (ROI), and 409,291 full length reads non-Chimeric (FLNC) sequences. Combined with second-generation sequencing (SGS), there were 2615, 6011, and 4617 differentially expressed genes (DEGs) in three comparisons. KEGG pathway analysis showed enrichment of ribosome, glutathione metabolism, and biosynthesis of amino acids are among the DEGs. The majority of transcription factors (TFs) from DEGs were AP2/ERF-ERF (37), C2H2 (32), and bHLH (22) bZIP (22), followed by C3H (19), MYB (18), WRKY (18), GRAS (16), and NAC (15). 32 C2H2 genes were differentially expressed in three groups. In addition, TFs annotated as C3H (19), MYB (18), GRAS (16), and NAC (15) also changed significantly in expression in the three comparisons. We found 24 genes participate in the abscisic acid (ABA) and auxin hormone signaling pathway in response to drought stress, and monitored the expression patterns of these related genes. Conclusion: The present study enhanced our understanding of the genetic diversity and complexity, and provides greater insight into the fundamental transcriptome reprogramming of Alfalfa under drought.

13.
Cell Discov ; 7(1): 103, 2021 Oct 31.
Article in English | MEDLINE | ID: mdl-34719679

ABSTRACT

Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, Pmeta = 8.36 × 10-8, OR = 1.29; rs7259428, 19q12, ZNF536, Pmeta = 7.58 × 10-8, OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, Pmeta = 1.95 × 10-8; rs2414487, 15q21.3, LOC145783, Pmeta = 4.53 × 10-9; rs2106525, 7q31.1, MDFIC, Pmeta = 6.24 × 10-9). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice.

14.
BMC Plant Biol ; 21(1): 249, 2021 May 31.
Article in English | MEDLINE | ID: mdl-34059002

ABSTRACT

BACKGROUND: Walnut anthracnose induced by Colletotrichum gloeosporioides is a disastrous disease affecting walnut production. The resistance of walnut fruit to C. gloeosporioides is a highly complicated and genetically programmed process. However, the underlying mechanisms have not yet been elucidated. RESULTS: To understand the molecular mechanism underlying the defense of walnut to C. gloeosporioides, we used RNA sequencing and label-free quantitation technologies to generate transcriptomic and proteomic profiles of tissues at various lifestyle transitions of C. gloeosporioides, including 0 hpi, pathological tissues at 24 hpi, 48 hpi, and 72 hpi, and distal uninoculated tissues at 120 hpi, in anthracnose-resistant F26 fruit bracts and anthracnose-susceptible F423 fruit bracts, which were defined through scanning electron microscopy. A total of 21,798 differentially expressed genes (DEGs) and 1929 differentially expressed proteins (DEPs) were identified in F26 vs. F423 at five time points, and the numbers of DEGs and DEPs were significantly higher in the early infection stage. Using pairwise comparisons and weighted gene co-expression network analysis of the transcriptome, we identified two modules significantly related to disease resistance and nine hub genes in the transcription expression gene networks. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the DEGs and DEPs revealed that many genes were mainly related to immune response, plant hormone signal transduction, and secondary metabolites, and many DEPs were involved in carbon metabolism and photosynthesis. Correlation analysis between the transcriptome data and proteome data also showed that the consistency of the differential expression of the mRNA and corresponding proteins was relatively higher in the early stage of infection. CONCLUSIONS: Collectively, these results help elucidate the molecular response of walnut fruit to C. gloeosporioides and provide a basis for the genetic improvement of walnut disease resistance.


Subject(s)
Colletotrichum , Juglans/microbiology , Plant Diseases/genetics , Plant Diseases/microbiology , Fruit/genetics , Fruit/microbiology , Juglans/genetics , Proteome , Transcriptome
15.
J Food Biochem ; 45(4): e13692, 2021 04.
Article in English | MEDLINE | ID: mdl-33686694

ABSTRACT

The stomach frequently suffers from acute gastric diseases after excessive ingestion of high-concentration alcoholic beverages, but little is known about the pathological mechanism by which ethanol affects the gastric mucosa. The aim of this study was to explore the mechanism of gastric epithelial cell death induced by relatively high concentrations of ethanol in vitro. Ethanol was demonstrated to induce rapid cell death in a concentration-dependent manner (Spearman r = .943, p = .017) and to activate the phosphorylation of key mediators in necroptosis pathway without influencing the key mediators in apoptosis pathway. The receptor-interacting serine-threonine kinase 1 (RIP1) kinase inhibitor necrostatin-1s (nec-1s) was found to reverse necroptotic cell death (from 65.5% necrosis to 35.8% necrosis, p = .006) and to inhibit the formation of necrosome complexes. These results indicate necroptosis rather than apoptosis pathway is an essential mechanism and is a novel therapeutic target in acute alcoholic gastric diseases. PRACTICAL APPLICATIONS: Alcohol consumption is related with a variety of diseases in many organs, but its pathological mechanism might be quite different due to the exposure extent between the stomach and other organs. Although there have been plenty of studies on alcoholic liver diseases and those in other organs, the pathological mechanism of alcoholic gastric diseases has been poorly investigated. Considering the unique distribution of ethanol on gastric mucosa, it is worthwhile to explore the specific cell death pattern of gastric epithelial cells under high-concentration ethanol treatment. Further investigation of the mechanisms of alcoholic gastric diseases would provide potential therapeutic strategies for the treatment of acute alcoholic gastric diseases as well as other acute alcoholic diseases.


Subject(s)
Ethanol , Necroptosis , Apoptosis , Epithelial Cells , Ethanol/toxicity , Stomach
16.
J Orthop Surg Res ; 16(1): 108, 2021 Feb 04.
Article in English | MEDLINE | ID: mdl-33541384

ABSTRACT

BACKGROUND: This study aimed to prepare the polymethylmethacrylate (PMMA) bone cement release system with different concentrations of enoxaparin sodium (ES) and to investigate the release characteristics of ES after loading into the PMMA bone cement. METHODS: In the experimental group, 40 g Palacos®R PMMA bone cement was loaded with various amount of ES 4000, 8000, 12,000, 16,000, 20,000, and 24,000 AXaIU, respectively. The control group was not loaded with ES. Scanning electron microscopy (SEM) was used to observe the surface microstructure of the bone cement in the two groups. In the experiment group, the mold was extracted continuously with pH7.4 Tris-HCL buffer for 10 days. The extract solution was collected every day and the anti-FXa potency was measured. The experiment design and statistical analysis were conducted using a quantitative response parallel line method. RESULTS: Under the SEM, it was observed that ES was filled in the pores of PMMA bone cement polymer structure and released from the pores after extraction. There was a burst effect of the release. The release amount of ES on the first day was 0.415, 0.858, 1.110, 1.564, 1.952, and 2.513, respectively, from the six groups with various ES loading amount of 4000, 8000, 12,000, 16,000, 20,000, and 24,000 AXaIU, all reaching the peak of release on the first day. The release decreased rapidly on the next day and entered the plateau phase on the fourth day. CONCLUSION: The prepared ES-PMMA bone cement has high application potential in orthopedic surgery. ES-PMMA bone cement shows good drug release characteristics. The released enoxaparin sodium has a local anti-coagulant effect within 24 h after application, but it will not be released for a long time, which is complementary to postoperative anti-coagulation therapy.


Subject(s)
Bone Cements , Drug Liberation , Enoxaparin , Polymethyl Methacrylate , Anticoagulants/administration & dosage , Bone Cements/chemistry , Enoxaparin/administration & dosage , Enoxaparin/pharmacology , Polymethyl Methacrylate/chemistry , Porosity , Tromethamine
17.
Appl Opt ; 60(36): 11066-11074, 2021 Dec 20.
Article in English | MEDLINE | ID: mdl-35201095

ABSTRACT

When measuring the form deviation of the gear tooth flank with laser interferometry, due to the limitation of the depth of field of the lens, focused and defocused regions exist in the interferogram simultaneously. The introduced errors that were generated by these defocused regions decrease the measurement accuracy. Therefore, the evaluation of definition for interferograms is necessary for image processing. However, the gradient of gray, which performs by fringes, makes it difficult for traditional algorithms to evaluate its definition. This paper proposes a method based on nonsubsampled contourlet transformation (NSCT) combined with fringe direction as weighting coefficients to solve the problem. First, the information about the directions of these fringes in interferograms was evaluated. Then, the NSCT method was applied to interferograms so that several sub-images in different scales and directions can be achieved. Based on these sub-images and directions information, an improved function for definition evaluation was conducted. Lastly, a series of simulations and experiments was carried out to verify its feasibility and accuracy.


Subject(s)
Algorithms , Image Processing, Computer-Assisted , Image Processing, Computer-Assisted/methods , Interferometry
18.
PLoS One ; 15(6): e0234085, 2020.
Article in English | MEDLINE | ID: mdl-32497140

ABSTRACT

Late embryogenesis abundant (LEA) proteins are widely involved in many adverse conditions among plants. In this study, we isolated a LEA4 gene from alfalfa (Medicago sativa L.) termed MsLEA4-4 via a homology cloning strategy. MsLEA4-4 encodes 166 amino acids, and the structural analysis showed that the gene contained five repeating TAQAAKEKTQQ amino acid motifs. There were a large number of α-helix in MsLEA4-4, and belongs to hydrophilic amino acid. Subcellular localization analysis showed that MsLEA4-4 was localized in the nucleus. The MsLEA4-4 promoter consisted of G-box and A-box elements, abscisic acid-responsive elements (ABREs), photo regulation and photoperiodic-controlling cis-acting elements, and endosperm expression motifs. The MsLEA4-4 overexpressing in Arabidopsis conferred late-germination phenotypes. Resistance of the overexpressed plants to abiotic stress significantly outperformed the wild-type (WT) plants. Under salt stress and abscisic acid treatment, with more lateral roots and higher chlorophyll content, the overexpressed plants has a higher survival rate measured against WT. Compared to those in the WT plants, the levels of soluble sugar and the activity of various antioxidant enzymes were elevated in the overexpressed plants, whereas the levels of proline and malondialdehyde were significantly reduced. The expression levels of several genes such as ABF3, ABI5, NCED5, and NCED9 increased markedly in the overexpressed plants compared to the WT under osmotic stress.


Subject(s)
Arabidopsis/genetics , Arabidopsis/physiology , Droughts , Medicago sativa/genetics , Oxidative Stress/genetics , Plant Proteins/genetics , Salt Stress/genetics , Amino Acid Sequence , Arabidopsis/growth & development , Arabidopsis/metabolism , Base Sequence , Cloning, Molecular , Gene Expression , Germination , Osmotic Pressure , Plant Proteins/chemistry , Promoter Regions, Genetic/genetics
19.
Soft Matter ; 16(15): 3705-3716, 2020 Apr 15.
Article in English | MEDLINE | ID: mdl-32232287

ABSTRACT

This study examines nonlinear rheological responses to uniaxial extension of two entangled polystyrene (PS) solutions and two PS melts. Several unusual characteristics are revealed. The pair of the PS solutions have the same number of entanglements per chain (because of the same concentration) but well separated effective glass transition temperatures Tg. When examined at a common effective rate of extension (e.g., the same Rouse-Weissenberg number WiR) and at a comparable distance from their respective Tg, the solution A with lower Tg, examined at a lower temperature, shows stronger stress responses when WiR > 1. At the same test temperature and a common WiR, the solution A is still found to display a stronger stress response than the solution B that is made of the same fraction of parent PS in a second solvent also made of oligomeric PS of higher molecular weight. Finally, there are two features intrinsic to each of the four PS samples. First, at the same WiR they show reduced stress level at a lower temperature. Second, at sufficiently high applied Hencky rates, they show limiting rate behavior, i.e., undergoing the same melt rupture independent of the applied rate. These remarkable rheological responses indicate major theoretical difficulties facing the subject of nonlinear extensional rheology of entangled polymers.

20.
Gene ; 726: 144193, 2020 Feb 05.
Article in English | MEDLINE | ID: mdl-31669647

ABSTRACT

OBJECTIVE: miR-199a-5p was increased during osteoblast differentiation, which may target and regulate TET2, a gene attracted a lot of attention in the osteoblast differentiation in the past few years. However, the role of miR-199a-5p in osteoblast differentiation by targeting TET2 is not established. METHODS: The correlation between miR-199a-5p and TET2 was verified through dual luciferase reporter assay, and their expressions in human bone marrow stromal cells (hBMSCs) during the osteoblast differentiation were detected. hBMSCs were transfected with TET2 siRNA, miR-199a-5p mimic or/and TET2 CRISPR activation plasmid., and then prepared for the induction of osteoblast differentiation, followed by alkaline phosphatase (ALP) and alizarin red staining, qRT-PCR and Western blotting. In vivo, ovariectomized (OVX) mice were injected with agomir-miR-199a-5p, antagomiR-199a-5p or/and TET2 siRNA to calculate the BMD and BV/TV ratio of mice, as well as to measure the expressions of osteogenesis-related genes in bone tissues. RESULTS: A gradual increase of miR-199a-5p was observed in hBMSCs during the induction of osteoblast differentiation, while TET2 expression was decreased. Besides, miR-199a-5p was reduced in the bone tissue of OVX mice, while TET2 was up-regulated. In addition, overexpression of miR-199a-5p and inhibition of TET2 augmented ALP activity in hBMSCs, with the enhanced calcification and the up-regulated expressions of Runx2, OSX and OCN, which also increased the quality of bone in OVX mice accompanying the enhancement BV/TV ratio, BMD and osteogenesis-related genes. CONCLUSION: MiR-199a-5p may promote the osteoblast differentiation and prevent OVX-induced osteoporosis by targeting TET2.


Subject(s)
Cell Differentiation/genetics , DNA-Binding Proteins/genetics , MicroRNAs/genetics , Osteoblasts/metabolism , Proto-Oncogene Proteins/genetics , Alkaline Phosphatase/genetics , Animals , Bone Marrow Cells/metabolism , Bone and Bones/metabolism , Calcification, Physiologic/genetics , Cells, Cultured , Dioxygenases , Female , Humans , Mesenchymal Stem Cells/metabolism , Mice , Mice, Inbred C57BL , Osteogenesis/genetics , Up-Regulation/genetics
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