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1.
FASEB J ; 38(5): e23526, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38430456

ABSTRACT

Germ cell development depends on the capacity of somatic Sertoli cells to undergo differentiation into a mature state and establish a germ cell-specific blood-testis barrier (BTB). The BTB structure confers an immunological barrier for meiotic and postmeiotic germ cells, and its dynamic permeability facilitates a transient movement of preleptotene spermatocytes through BTB to enter meiosis. However, the regulatory factors involved in Sertoli cell maturation and how BTB dynamics coordinate germ cell development remain unclear. Here, we found a histone deacetylase HDAC3 abundantly expresses in Sertoli cells and localizes in both cytoplasm and nucleus. Sertoli cell-specific Hdac3 knockout in mice causes infertility with compromised integrity of blood-testis barrier, leading to germ cells unable to traverse through BTB and an accumulation of preleptotene spermatocytes in juvenile testis. Mechanistically, nuclear HDAC3 regulates the expression program of Sertoli cell maturation genes, and cytoplasmic HDAC3 forms a complex with the gap junction protein Connexin 43 to modulate the BTB integrity and dynamics through regulating the distribution of tight junction proteins. Our findings identify HDAC3 as a critical regulator in promoting Sertoli cell maturation and maintaining the homeostasis of the blood-testis barrier.


Subject(s)
Blood-Testis Barrier , Histone Deacetylases , Sertoli Cells , Animals , Male , Mice , Blood-Testis Barrier/metabolism , Cell Differentiation , Sertoli Cells/metabolism , Spermatocytes/metabolism , Spermatogenesis/genetics , Testis/metabolism , Tight Junctions/metabolism , Histone Deacetylases/genetics , Histone Deacetylases/metabolism
2.
Small ; 20(14): e2308600, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37974554

ABSTRACT

The rise of MXene-based materials with fascinating physical and chemical properties has attracted wide attention in the field of biomedicine, because it can be exploited to regulate a variety of biological processes. The biomedical applications of MXene are still in its infancy, nevertheless, the comprehensive evaluation of MXene's biosafety is desperately needed. In this review, the composition and the synthetic methods of MXene materials are first introduced from the view of biosafety. The evaluation of the interaction between MXene and cells, as well as the safety of different forms of MXene applied in vivo are then discussed. This review provides a basic understanding of MXene biosafety and may bring new inspirations to the future applications of MXene-based materials in biomedicine.


Subject(s)
Containment of Biohazards , Nitrites , Transition Elements
3.
J Appl Microbiol ; 133(5): 2979-2992, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35943823

ABSTRACT

AIMS: This study aimed to isolate and identify entomopathogenic fungi (EPF) from fungus-infected Ostrinia furnacalis larvae, screen their bio-efficacy against O. furnacalis, and select the most suitable virulent native EPF for biocontrol agent development. METHODS AND RESULTS: The occurrence of EPF isolated from various maize production regions in Xinjiang was investigated. Of 13,864 O. furnacalis cadavers surveyed, 536 were selected, and of 136 fungal specimens collected, 14 species were identified. Four fungal isolates were highly pathogenic to O. furnacalis: Aspergillus sp., Lecanicillium attenuatum, Beauveria bassiana and Penicillium polonicum. The Aspergillus sp. was the most abundant (42.25% distribution frequency). Bioassay results revealed that it was as pathogenic as B. bassiana (positive control), with 96.58% lethality against O. furnacalis (LC50 : 1.40 × 104 conidia ml-1 , LT50 : 3.41 days). Through morphological examination and rDNA-benA and rDNA-CaM homogeneity analyses, the isolate was identified as Aspergillus nomius. CONCLUSIONS: Four EPF species were highly pathogenic, with A. nomius being the most prevalent in Xinjiang. A. nomius is a potential biocontrol agent. SIGNIFICANCE AND IMPACT OF STUDY: For sustainable prevention and control of O. furnacalis infestation, identifying biocontrol agents with high virulence against O. furnacalis is crucial. The findings of this study support the development of EPF-based biocontrol approaches.


Subject(s)
Beauveria , Moths , Animals , Zea mays/genetics , Larva/microbiology , Beauveria/genetics , DNA, Ribosomal
4.
Stem Cells ; 37(2): 247-256, 2019 02.
Article in English | MEDLINE | ID: mdl-30353595

ABSTRACT

The characteristics of mesenchymal stromal cells (MSCs) which derived from multiple myeloma (MM) patients are typically impaired in osteogenic differentiation. However, the underlying molecular mechanisms need to be further investigated. lncRNAs are emerging as critical regulation molecules in oncogenic pathways. In this study, we identified that bioactive lncRNA HOXC-AS3, which is transcribed in opposite to HOXC10, was presented in MSCs derived from bone marrow (BM) of MM patients (MM-MSCs). HOXC-AS3 was able to interact with HOXC10 at the overlapping parts and this interaction increased HOXC10 stability, then promoted its expression, conferring osteogenesis repression to MM-MSCs. In mouse models, intravenously administered siHOXC-AS3 was proven to be effective in prevention of bone loss, sustained by both anticatabolic activities and bone-forming. These data showed that lncHOXC-AS3 was required for osteogenesis in BM-MSCs by enhancing HOXC10 expression. Our finding thus unveils a novel insight for the potential clinical significance of lncRNA HOXC-AS3 as a therapeutic target for bone disease in MM. Stem Cells 2019;37:247-256.


Subject(s)
Homeodomain Proteins/metabolism , Mesenchymal Stem Cells/metabolism , Multiple Myeloma/metabolism , Oligonucleotides, Antisense/metabolism , Osteoblasts/metabolism , RNA, Long Noncoding/metabolism , Animals , Case-Control Studies , Cell Differentiation/physiology , Cell Line, Tumor , Cells, Cultured , Female , Heterografts , Homeodomain Proteins/genetics , Humans , Mesenchymal Stem Cells/cytology , Mice , Multiple Myeloma/genetics , Multiple Myeloma/pathology , Oligonucleotides, Antisense/genetics , Osteogenesis , RNA, Long Noncoding/genetics , Transfection , Up-Regulation
5.
Talanta ; 281: 126821, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39255622

ABSTRACT

Bioluminescence is a natural process where biological organisms produce light through chemical reactions. These reactions predominantly occur between small-molecule substrates and luciferase within bioluminescent organisms. Bioluminescence imaging (BLI) has shown significant potential in biomedical research owing to its non-invasive, real-time observation and quantification. In this review, we introduced the chemical mechanism of bioluminescent systems and categorized several strategies that successfully addressed the native limitations, including improvements on the chemical structures of luciferase-luciferin bioluminescence system and bioluminescence resonance energy transfer (BRET) methods. In addition, we also reviewed and summarized recent advances in bioimaging applications. We hope that this review can provide effective guidance for the development and application of bioluminescent systems in the field of bioimaging.

6.
JACC Adv ; 3(1): 100737, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38939805

ABSTRACT

Background: A simple ambulatory measure of cardiac function could be helpful for monitoring heart failure patients. Objectives: The purpose of this paper was to determine whether a novel pulse waveform analysis using data obtained by our developed multisensor-ambulatory blood pressure monitoring (ABPM) device, the 'Sf/Am' ratio, is associated with echocardiographic left ventricular ejection fraction (LVEF). Methods: Multisensor-ABPM was conducted twice at baseline in 20 heart failure (HF) patients with HF-reduced LVEF or HF-preserved LVEF (median age 66 years, male 65%) and over a 6- to 12-month follow-up after patient-tailored treatment. We assessed the changes in the pulse waveform index Sf/Am and LVEF that occurred between the baseline and follow-up. The Sf/Am consists of the area of the ejection part in the square forward wave (Sf) and the amplitude of the measured wave (Am). We divided the patients into the recovered (n = 11) and not-recovered (n = 9) groups defined by a ≥10% increase in LVEF. Results: Although the ambulatory BP levels and variabilities did not change in either group, the Sf/Am increased significantly in the recovered group (baseline 21.4 ± 4.5; follow-up, 25.6 ± 3.7, P = 0.004). The not-recovered group showed no difference between the baseline and follow-up. The follow-up/baseline Sf/Am ratio was significantly associated with the LVEF ratio (r = 0.469, P = 0.037). The Sf/Am was significantly correlated with the LVEF in overall measurements (n = 40, r = 0.491, P = 0.001). Conclusions: These results demonstrated that a novel noninvasive pulse waveform index, the Sf/Am measured by multisensor-ABPM is associated with LVEF. The Sf/Am may be useful for estimating cardiac function.

7.
Front Oncol ; 14: 1337219, 2024.
Article in English | MEDLINE | ID: mdl-38380369

ABSTRACT

Background: Laparoscopic total mesorectal excision (LaTME) is standard surgical methods for rectal cancer, and LaTME operation is a challenging procedure. This study is intended to use machine learning to develop and validate prediction models for surgical difficulty of LaTME in patients with rectal cancer and compare these models' performance. Methods: We retrospectively collected the preoperative clinical and MRI pelvimetry parameter of rectal cancer patients who underwent laparoscopic total mesorectal resection from 2017 to 2022. The difficulty of LaTME was defined according to the scoring criteria reported by Escal. Patients were randomly divided into training group (80%) and test group (20%). We selected independent influencing features using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression method. Adopt synthetic minority oversampling technique (SMOTE) to alleviate the class imbalance problem. Six machine learning model were developed: light gradient boosting machine (LGBM); categorical boosting (CatBoost); extreme gradient boost (XGBoost), logistic regression (LR); random forests (RF); multilayer perceptron (MLP). The area under receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity and F1 score were used to evaluate the performance of the model. The Shapley Additive Explanations (SHAP) analysis provided interpretation for the best machine learning model. Further decision curve analysis (DCA) was used to evaluate the clinical manifestations of the model. Results: A total of 626 patients were included. LASSO regression analysis shows that tumor height, prognostic nutrition index (PNI), pelvic inlet, pelvic outlet, sacrococcygeal distance, mesorectal fat area and angle 5 (the angle between the apex of the sacral angle and the lower edge of the pubic bone) are the predictor variables of the machine learning model. In addition, the correlation heatmap shows that there is no significant correlation between these seven variables. When predicting the difficulty of LaTME surgery, the XGBoost model performed best among the six machine learning models (AUROC=0.855). Based on the decision curve analysis (DCA) results, the XGBoost model is also superior, and feature importance analysis shows that tumor height is the most important variable among the seven factors. Conclusions: This study developed an XGBoost model to predict the difficulty of LaTME surgery. This model can help clinicians quickly and accurately predict the difficulty of surgery and adopt individualized surgical methods.

8.
Sci Rep ; 14(1): 6860, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38514725

ABSTRACT

When testing earthquake simulation shaking tables, it is commonly assumed that the test load, table, and actuator are integrated, which differs significantly from the actual situation and negatively impacts the accuracy of system waveform reproduction. This paper simplifies the connection between the three as a spring-damping model for simulation modeling. The effects of different load mass, different connection intrinsic frequency, different connection damping ratios, and other factors on the control performance of the system are analyzed, and based on the results of the analysis, a method to improve the effects of the connection characteristics on the performance of the system, called flexible connection reaction force compensation algorithm, is proposed. Resonance peaks caused by flexible connections reduce the effective bandwidth. To broaden the bandwidth and enhance system stability, the paper introduces a flexible connection force compensation algorithm based on a multi-parameter control algorithm to compensate for the interaction force caused by the connection characteristics. This compensation strategy expands the effective bandwidth, eliminates resonance peaks, improves the waveform correlation coefficient (CC), and reduces the root-mean-square error (RMSE).

9.
J Colloid Interface Sci ; 661: 740-749, 2024 May.
Article in English | MEDLINE | ID: mdl-38325172

ABSTRACT

Perovskite nanocrystals (PNCs) have attracted extensive attention for their potential applications in biology. However, only a handful of PNCs have been scrutinized in the biological domain due to issues such as instability, poor dispersion, and size inhomogeneity in polar solvents. The development of dual-functional perovskite nanomaterials with hydrogen sulfide (H2S) sensing and antibacterial capabilities is particularly intriguing. In this study, we prepared chiral quasi-two-dimensional (quasi-2D) perovskite nanomaterials, Bio(S-PEA)2CsPb2Br7 and Bio(R-PEA)2CsPb2Br7, that were uniformly dispersed in aqueous media. The effective encapsulation of methoxypolyethylene glycol amine (mPEG-NH2) improved water stability and uniformity of particle size. Circular dichroism (CD) signals were created by the successful insertion of chiral cations. These perovskites as probes showed a rapid and sensitive fluorescence quenching response to H2S, and the effect of imaging detection was observed at the Escherichia coli (E. coli) level. As antibacterial agents, their pronounced positive charge properties facilitated membrane lysis and subsequent E. coli death, indicating a significant antibacterial effect. This work has preliminary explored the application of chiral perovskites in biology and provides insight into the development of bifunctional perovskite nanomaterials for biological applications.


Subject(s)
Calcium Compounds , Hydrogen Sulfide , Oxides , Polyethylene Glycols , Titanium , Hydrogen Sulfide/pharmacology , Escherichia coli , Water , Anti-Bacterial Agents/pharmacology
10.
J Phys Chem Lett ; 15(34): 8721-8727, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39162198

ABSTRACT

The energy required for spin-orbit excitation plays a critical role in understanding translational-to-electronic energy conversion, particularly in chemical reactions involving changes in spin states. This is particularly important for transition metal atoms possessing d-orbitals, which result in multiple spin-orbit split energy levels at low energies. The accurate identification and characterization of spin-orbit transitions in such species require advanced experimental techniques and theoretical support. In this study, the spin-orbit excited collisions of Y(2D3/2) with rare gas atoms Ne, Ar, and Kr leading to Y(2D5/2) were observed using laser-ablated crossed-beam and time-sliced ion velocity mapping imaging techniques. Through a comparison of the forward angular distributions of Y(2D3/2) to the backward and sideway scattering distributions of Y(2D5/2) from elastic and inelastic collisions of Y(2D) with rare gas atoms, this study reveals that the spin-orbit electronic excitation occurs with high collision energy and low impact parameters from backward and sideway collisions. The effectiveness of the spin-orbit excitation process is strongly dependent on the collision energy or temperature, suggesting that energy requirements of the process have to be considered in chemical reactions involving changes in spin states.

11.
Food Chem ; 460(Pt 1): 140468, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39053276

ABSTRACT

Porphyra sensu lato, a highly valuable edible seaweed renowned for its distinctive umami taste, undergoes significant taste variations during the harvest cycle, affecting product quality and pricing. In this study, umami-related metabolites in Pyropia haitanensis were investigated at different harvesting times using GC-MS metabolomic, targeted LC-MS analysis, and an electronic tongue taste evaluation. High concentrations of compounds, including glutamic acid, aspartic acid, and inosine 5'-monophosphate, were identified as the main contributors to the overall umami profile. The concentrations of the compounds and umami-enhancing substances, such as sugars, were negatively correlated as the harvesting period extended. The early harvested P. haitanensis exhibited a superior umami taste, which gradually decreased with subsequent harvest time. Proline, a known cold-resistance metabolite, accumulated as the seawater temperature decreased and the harvest period progressed. These findings provide insights into the optimal cultivation and harvesting practices for maintaining umami quality in P. haitanensis products.


Subject(s)
Metabolomics , Taste , Humans , Male , Adult , Gas Chromatography-Mass Spectrometry , Female , Porphyra/chemistry , Porphyra/metabolism , Porphyra/growth & development , Seaweed/metabolism , Seaweed/chemistry , Seaweed/growth & development , Young Adult , Flavoring Agents/metabolism , Flavoring Agents/chemistry
12.
Science ; : eadj8172, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39208083

ABSTRACT

Despite continuous expansion of the RNA-binding protein (RBP) world, there is a lack of systematic understanding of RBPs in mammalian testis, which harbors one of the most complex tissue transcriptomes. We adapted RNA interactome capture to mouse male germ cells, building an RBP atlas characterized by multiple layers of dynamics along spermatogenesis. Trapping of RNA-crosslinked peptides showed that the glutamic acid-arginine (ER) patch, a residue-coevolved polyampholytic element present in coiled-coils, enhances RNA binding of its host RBPs. Deletion of this element in NONO (non-POU domain-containing octamer-binding protein) led to a defective mitosis-to-meiosis transition due to compromised NONO-RNA interactions. Whole-exome sequencing of over 1000 infertile men revealed a prominent role of RBPs in the human genetic architecture of male infertility and identified risk ER patch variants.

13.
Front Psychol ; 14: 1278899, 2023.
Article in English | MEDLINE | ID: mdl-38187415

ABSTRACT

As positive psychology is imported into second language acquisition, we witness the increasing interest in the research of English enjoyment. Therefore, investigating the antecedents of English enjoyment is of paramount importance. Although internal and external factors have been scrutinized by researchers, scarce studies have explored the effect of peer support and regulatory emotional self-efficacy on English enjoyment. Thus, this study was designed to further clarify the association between these two constructs and English enjoyment. A questionnaire involving the three variables of peer support, English enjoyment, and regulatory emotional self-efficacy was administered to 324 non-English major undergraduate students at a comprehensive university in Eastern China. Correlation analysis and mediation effect tests indicated that peer support and regulatory emotional self-efficacy positively predicted English enjoyment, and regulatory emotional self-efficacy played a mediating role between peer support and English enjoyment. This study highlights the significance of peer support and positive emotions in second language learning and extends our understanding of enhancing students' learning enjoyment through teachers' positive intervention to facilitate peer support and regulatory emotional self-efficacy.

14.
Anal Chim Acta ; 1241: 340778, 2023 Feb 08.
Article in English | MEDLINE | ID: mdl-36657871

ABSTRACT

Endogenous peroxynitrite plays a very important role in the regulation of life activities. However, validated tools for ONOO- tests are currently insufficient. We designed a fluorescent probe TPA-F-NO2 with a low fluorescence background in water based on the D-π-A structure for the imaging of endogenous ONOO- in living cells. TPA-F-NO2 can realize the naked eye detection of ONOO- due to the obvious color change. TPA-F-NO2 has the advantages of large stokes shift, high signal-to-noise ratio, high selectivity and sensitivity. The quantitative detection can be achieved in the range of 0-14 µM ONOO-. Due to its solvatochromic characteristics, TPA-F-NO2 has the potential to be used in OLEDs and other fields. In addition, 4-methylumbelliferone has a wide range of anticancer effects as an inhibitor of hyaluronic acid. We prepared TPA-MU-NPs by assembling TPA-F-NO2 and 4-methylumbelliferone. It also endows TPA-MU-NPs with ONOO- imaging function and anti-proliferation effect on breast cancer cells and other cells. This 'probe-drug' assembly strategy provides ideas for the design and optimization of dual-functional probes.


Subject(s)
Fluorescent Dyes , Peroxynitrous Acid , Humans , Fluorescent Dyes/toxicity , Fluorescent Dyes/chemistry , Peroxynitrous Acid/chemistry , Hymecromone , Nitrogen Dioxide , Optical Imaging
15.
Nanoscale ; 15(4): 1947-1952, 2023 Jan 27.
Article in English | MEDLINE | ID: mdl-36625286

ABSTRACT

Low-temperature fuel cells have great application potential in electric vehicles and portable electronic devices, which need advanced electrocatalysts. Controlling the composition and morphology of electrocatalysts can effectively improve their catalytic performance. In this work, a Rh metallene (Rhlene)-supported Pt nanoparticle (Pt/Rhlene) electrocatalyst is successfully synthesized by a simple chemical reduction method, in which ultra-small Pt nanoparticles are uniformly attached to the Rhlene surface due to the high surface area of Rhlene. Pt/Rhlene reveals a 3.60-fold Pt-mass activity enhancement for the ethylene glycol oxidation reaction in alkaline solution compared with commercial Pt black, and maintains high stability and excellent poisoning-tolerance during electrocatalysis, owing to the specific physical/chemical properties of Rhlene. The superior electrocatalytic performance of Pt/Rhlene may open an avenue to synthesize other metallene-supported noble metal nanoparticle hybrids for various electrocatalytic applications.

16.
Virulence ; 14(1): 2265108, 2023 12.
Article in English | MEDLINE | ID: mdl-37941402

ABSTRACT

The control of Ostrinia furnacalis, a major pest of maize in Xinjiang, is challenging owing to the occurrence of resistant individuals. Entomopathogenic fungi (EPF) are natural insect regulators used as substitutes for synthetic chemical insecticides. The fungus Aspergillus nomius is highly pathogenic to O. furnacalis; however, its virulence characteristics have not been identified. This study aimed to analyse the lethal efficacy, mode of infection on the cuticle, and extracellular enzyme activity of A. nomius against O. furnacalis. We found that the mortality and mycosis of O. furnacalis were dose-dependent when exposed to A. nomius and varied at different life stages. The egg-hatching and adult emergence rates decreased with an increase in conidial suspension. The highest mortality (83.33%, 7 d post-infection [DPI]) and mycosis (74.33%, 7 DPI) and the lowest mortality response (8.52 × 103 conidia mL-1) and median lethal time (4.91 d) occurred in the 3rd instar larvae of O. furnacalis. Scanning electron microscopy indicated that numerous conidia germination and infection structure formation may have contributed to the high pathogenicity of A. nomius against O. furnacalis. There were significant correlations between O. furnacalis mortality and the activities of extracellular protease, lipase, and chitinase of A. nomius. This study revealed the infection process of the highly pathogenic A. nomius against O. furnacalis, providing a theoretical basis and reference for strain improvement and field application of EPF.


Subject(s)
Lepidoptera , Moths , Humans , Animals , Lepidoptera/microbiology , Zea mays , Virulence , Moths/physiology , Aspergillus , Larva/physiology
17.
PLoS One ; 17(12): e0279092, 2022.
Article in English | MEDLINE | ID: mdl-36576934

ABSTRACT

It is difficult to accurately establish a model of the real mesa system. Furthermore, a model of a seismic simulation vibration table array system is critical to increasing the accuracy of seismic testing in laboratory settings. Herein a model of the nine subarray shaking table system is identified by recursive extension of the least square method, which is used to accurately identify the structure parameters by simulation of the structure assuming a single degree-of-freedom. Then, through the displacement of the empty shaking table and the application of the recursive least squares algorithm, the model of the seismic simulation vibration table array is established. Through this study, the vibration table model of different construction forms can be obtained, and the parameters that are difficult to measure for some complex structures can effectively be determined.


Subject(s)
Algorithms , Vibration , Computer Simulation , Least-Squares Analysis
18.
Food Chem ; 394: 133477, 2022 Nov 15.
Article in English | MEDLINE | ID: mdl-35728469

ABSTRACT

A pulsed electric field (PEF) treatment exhibits different effects on trypsin; however, the mechanism of enzyme activation remains unclear. Herein, chemical experiments combined with molecular dynamics simulations revealed the mechanism of trypsin activation by PEF treatment at the molecular level. The results indicated that compared with the values at 0 kV/cm, the enzyme activity, Vmax, and Kcat at 20 kV/cm increased by 9.30%, 4.74%, and 4.30%, respectively, and Km decreased by 11.14%, indicating an improved interaction between the enzyme and substrate. The simulation results revealed that PEF treatment increased the number of molecular hydrogen bonds and the solvent-accessible surface area, while decreasing the rotation radius and random coil content by 5.00% and 3.37%, respectively. Molecular docking indicated that PEF treatment altered the active center and increased the affinity between the enzyme and substrate. The simulation results were consistent with those of the spectroscopic experiments conducted on trypsin after PEF treatment.


Subject(s)
Electricity , Molecular Dynamics Simulation , Hydrogen Bonding , Molecular Docking Simulation , Trypsin
19.
Chem Commun (Camb) ; 58(79): 11139-11142, 2022 Oct 04.
Article in English | MEDLINE | ID: mdl-36106578

ABSTRACT

Electrostatically assembled ultrathin rhodium nanosheet-gold nanowire nanocomposites (Rh-Au CNSs) were used as an advanced electrocatalyst for the methanol oxidation reaction, which revealed a mass activity of 355 mA mgRh-1 at 0.607 V potential, much higher than single metal Rh nanosheets (273 mA mgRh-1) and commercial Rh nanoparticles (165 mA mgRh-1).

20.
Genes Genomics ; 44(12): 1577-1591, 2022 12.
Article in English | MEDLINE | ID: mdl-35567714

ABSTRACT

BACKGROUND: It has been well established that the long non-coding RNAs (lncRNAs) plays a critical role in tumor progression. However, the function of these transcripts and mechanisms responsible for their deregulation in colorectal cancer (CRC) remain to be investigated. OBJECTIVE: To explore the potential effect and regulation mechanism of lncRNA H19X in colorectal cancer. METHODS: We predicted and validated long non-coding RNA H19X from microarray data of colorectal cancer tissues. In addition, the biological behaviors of H19X and miR-503-5p on CRC were examined in vitro and in vivo, including MTT, colony formation assay, Hoechst33342 and transwell assay. The mRNA and protein levels of KN Motif and Ankyrin Repeat Domains 1 (KANK1) were analyzed by Quantitative real-time PCR (qRT-PCR), western blotting (WB) assay. Moreover, bioinformatics tools and dual-luciferase reporter assay were applied to demonstrate the relationship between KANK1 and miR-503-5p. RESULTS: H19X was remarkably up-regulated in CRC tissues. Its expression related to tumor size (p = 0.041), lymph node metastasis (p = 0.037), distal metastasis (p = 0.028), advanced TNM stage (p = 0.034) and poor survival in CRC. H19X acted as an oncogenic lncRNA that induced CRC cell proliferation, invasion and metastasis. Through a number of functional studies, we found that H19X silencing inhibited the malignance phenotype of cancer cells through loss of miR-503-5p. Further studies demonstrated that miR-503-5p was involved in the progression of CRC by directly regulating the downstream target KANK1. CONCLUSION: Collectively, the findings of the present study indicate H19X/miR-503-5p/KANK1 axis has critical role in the progression of colorectal cancer, providing an effective prognostic indicator and promising target in treatment of colorectal cancer.


Subject(s)
Colorectal Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Neoplasm Invasiveness/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Cell Movement/genetics , Colorectal Neoplasms/metabolism , Cell Line, Tumor , Carcinogenesis/genetics , Cytoskeletal Proteins/metabolism , Adaptor Proteins, Signal Transducing
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