230 results on '"Cui XS"'
Search Results
2. IDH2 and GLUD1 depletion arrests embryonic development through an H4K20me3 epigenetic barrier in porcine parthenogenetic embryos.
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Zhan CL, Lu QY, Lee SH, Li XH, Kim JD, Lee GH, Sim JM, Song HJ, Jin YY, and Cui XS
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- Animals, Swine embryology, Histones metabolism, Histones genetics, Gene Expression Regulation, Developmental, Gene Knockdown Techniques, Isocitrate Dehydrogenase genetics, Isocitrate Dehydrogenase metabolism, Embryonic Development, Epigenesis, Genetic, Glutamate Dehydrogenase metabolism, Glutamate Dehydrogenase genetics, Parthenogenesis
- Abstract
Isocitrate dehydrogenase 2 (IDH2) and glutamate dehydrogenase 1 (GLUD1) are key enzymes involved in the production of α-ketoglutarate (α-KG), a metabolite central to the tricarboxylic acid cycle and glutamine metabolism. In this study, we investigated the impact of IDH2 and GLUD1 on early porcine embryonic development following IDH2 and GLUD1 knockdown (KD) via double-stranded RNA (dsRNA) microinjection. Results showed that KD reduced α-KG levels, leading to delayed embryonic development, decreased blastocyst formation, increased apoptosis, reduced blastomere proliferation, and pluripotency. Additionally, IDH2 and GLUD1 KD induced abnormally high levels of trimethylation of lysine 20 of histone H4 (H4K20me3) at the 4-cell stage, likely resulting in transcriptional repression of embryonic genome activation (EGA)-related genes. Notably, KD of lysine methyltransferase 5C ( KMT5C ) and supplementation with exogenous α-KG reduced H4K20me3 expression and partially rescued these defects, suggesting a critical role of IDH2 and GLUD1 in the epigenetic regulation and proper development of porcine embryos. Overall, this study highlights the significance of IDH2 and GLUD1 in maintaining normal embryonic development through their influence on α-KG production and subsequent epigenetic modifications.
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- 2024
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3. ERK5 is essential for early porcine embryonic development by maintaining Endoplasmic Reticulum homeostasis.
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Lee GH, Lee SH, Li XH, Lu QY, Zhan CL, Kim JD, Sim JM, Song HJ, Sun MH, and Cui XS
- Abstract
Extracellular signal-regulated kinase 5 (ERK5), a mitogen-activated protein kinase (MAPK) family member, plays an important role in various biological processes, such as proliferation, apoptosis, differentiation, survival, and cell regulation. However, studies on the effects of ERK5 on porcine preimplantation embryos are limited. In this study, to determine the function of ERK5 during porcine embryo development, ERK5 function was inhibited by adding the ERK5 inhibitor JWG-071. The ERK5 mRNA and protein expression levels tended to decrease from the 4-cell stage compared to the 1-cell and 2-cell stages, suggesting that ERK5 is the maternal gene. During embryonic development in pigs, adding 5 μM of JWG-071 significantly reduced the phosphorylation of ERK5 and the blastocyst development rate (control: 53.44 ± 8.38 %; treatment: 26.65 ± 3.40 %). Additionally, ERK5 inhibition increased the expression of UPR-related proteins, glucose-regulated protein (GRP78), and C/EBP homologous protein (CHOP) by inducing ER stress. Compared to the control group, the expression of the autophagy-related proteins LC3 and ATG7 was significantly increased in the ERK5 inhibition group, indicating that the inhibition of ERK5 induced autophagy. In addition, ERK5 inhibition increased the expression of BAX, a pro-apoptotic gene, resulting in apoptosis. In conclusion, the results show that ERK5 inhibition during porcine embryonic development induces autophagy and apoptosis by increasing ER stress, resulting in a negative effect on embryonic development in pigs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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4. Effects of calcium lactate on in vitro fertilization and embryonic development in cattle.
- Author
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Kim BM, Lee SH, Heo G, Kim JD, Lee GH, Sim JM, Lim KT, and Cui XS
- Abstract
Objective: Growing demand for embryo transfer is steadily expanding and further studies on in vitro fertilization of cattle. To assess the effect of calcium lactate by replacing Tyrode's Albumin Lactate Pyruvate (TALP) medium composition during fertilization and embryonic development., Methods: Sodium lactate and CaCl2 were replaced with 2.0, 3.0, 4.5 mM calcium lactate for TALP medium during fertilization in Experiment 1. In Experiment 2, the concentrations of sodium lactate and CaCl2 were re-modified as control, in comparison with the same concentration of calcium lactate at 4.5 mM. Zygotes were moved to sequential media to match early-and late-stage environments. Embryonic development was examined on day 8 after insemination., Results: 4.5 mM calcium lactate enhanced the rate of fertilization and blastocyst formation (p<0.0001, p<0.01, respectively). It represented differences in the ROS (p<0.01) and GSH levels (p<0.05) and increased blastocyst diameter and total cell number (p<0.05). In Experiment 2, fertilization (p<0.05) and blastocyst formation rates (p<0.01) were increased in 4.5mM calcium lactate under same concentration effect of sodium lactate and CaCl2. Additionally, it reduced the ROS (p<0.01) and increased the GSH levels (p<0.05), leading increase embryo quality., Conclusion: The replacement of calcium lactate in TALP medium enhances fertilization and embryonic development while also improving oxidative stress. Specifically, it has been determined that a concentration of 4.5 mM calcium lactate is the most effective, irrespective of the varying concentrations of sodium lactate and CaCl2. This study presents a novel formulation of a modified TALP medium intended for implantation withing the bovine embryo industry. The current implications of the study are discussed in relation to previously stated objectives and hypotheses.
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- 2024
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5. Decreased in Mitochondrial Complex I Subunit NDUFS2 Is Critical for Oocyte Quality During Postovulatory Aging in Pigs.
- Author
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Zhou D, Lee SH, Li XH, Kim JD, Lee GH, Sim JM, and Cui XS
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- Animals, Swine, Female, Aging physiology, Gene Knockdown Techniques, NADH Dehydrogenase metabolism, NADH Dehydrogenase genetics, Oocytes metabolism, Oocytes physiology, Electron Transport Complex I metabolism, Electron Transport Complex I genetics, Mitochondria metabolism
- Abstract
The levels of nicotinamide adenine dinucleotide (NADH) dehydrogenase [ubiquinone] iron-sulfur protein 2 (NDUFS2, a subunit of NADH dehydrogenase) decrease in aged tissues, and these reductions may be partly associated with age-related conditions such as Parkinson's disease. Aging leads to many mitochondrial defects, such as biogenesis disruption, dysfunction, defects in the mitochondrial membrane potential, and production of reactive oxygen species, that may be highly related to NDUFS2 expression. The relationship between NDUFS2 and postovulatory oocyte aging in pigs remains unknown. In this study, we investigated changes in NDUFS2 expression during postovulatory aging (POA). Furthermore, NDUFS2 was knocked down via dsRNA microinjection at the MII stage to evaluate the effects on mitochondrial-related processes during POA. The mRNA expression of NDUFS2 decreased significantly after 48-h aging compared with that in fresh oocytes. NDUFS2 knockdown (KD) significantly impaired the maintenance of oocyte morphology and blastocyst development of embryos after POA. The levels of PGC1α (mitochondrial biogenesis-related proteins) decreased significantly after NDUFS2 KD, while the level of GSNOR, a protein denitrosylase, was reduced by NDUFS2 KD after 48 h of aging. These data suggest that NDUFS2 is vital for maintaining the oocyte quality during POA in pigs., Competing Interests: Conflict of Interest: The authors declare that they have no competing interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Microscopy Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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6. Comparative study of PGCs cultivation systems HiS and FAcs: a transcriptomic and cellular biology perspective.
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Niu YJ, Zheng D, Liu G, Ren W, Wu G, Peng Y, Wu J, Jin K, Zuo Q, Li G, Han W, Cui XS, Chen G, and Li B
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- Animals, Flow Cytometry veterinary, Cell Culture Techniques veterinary, Cell Biology, Chickens genetics, Transcriptome, Germ Cells
- Abstract
In chicken, primordial germ cells (PGC) are crucial for the preservation and manipulation of genetic resources in poultry production. The HiS and FAcs culture systems are two important methods for the in vitro cultivation of chicken PGCs. The purpose of this study was to compare and analyze the two cultivation systems for PGCs (His and FAcs culture systems) to assess their efficacy and applicability in supporting PGC growth, maintaining PGC characteristics, and lineage transmission ability. The study found that both HiS and FAcs culture systems could maintain the basic biological characteristics of chicken PGCs, including the simultaneous expression of pluripotency and reproductive marker genes, as well as the presence of abundant glycogen granules. Subsequently, we identified 2,145 differentially expressed genes (DEG) through RNA sequencing. GO and KEGG analysis revealed a large number of DEGs enriched in the cell adhesion and calcium ion binding pathways, and the analysis found that these genes maintained a higher level in HiS-PGCs. Further personalized analysis found that the regulatory genes for maintaining PGC pluripotency were highly expressed in HiS-PGCs, while germ cell-related genes showed similar expression in both systems. Additionally, through RNA sequencing data and cell proliferation ability, it was found that PGCs in the FAcs system had a higher proliferation rate and a faster cell cycle. Finally, it was discovered that the expression of cell migration-related genes was maintained at a higher level in HiS-PGCs, but the migration efficiency of HiS-PGCs did not show a significant difference compared to FAcs-PGCs. These results suggest that both HiS and FAcs culture systems can maintain the proliferation and basic characteristics of chicken PGCs, but differences exist in cell proliferation, pluripotency regulation, and cell adhesion. These findings provide new information for optimizing PGC cultivation systems and are important for the preservation and genetic improvement of chicken PGCs., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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7. Reconceptualization of immune checkpoint inhibitor-associated gastritis.
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Deng YF, Cui XS, and Wang L
- Subjects
- Humans, Immunotherapy adverse effects, Immunotherapy methods, Neoplasms drug therapy, Neoplasms immunology, Immune Checkpoint Inhibitors adverse effects, Gastritis immunology, Gastritis chemically induced, Gastritis diagnosis
- Abstract
In recent years, with the extensive application of immunotherapy in clinical practice, it has achieved encouraging therapeutic effects. While enhancing clinical efficacy, however, it can also cause autoimmune damage, triggering immune-related adverse events (irAEs). Reports of immunotherapy-induced gastritis have been increasing annually, but due to its atypical clinical symptoms, early diag-nosis poses a certain challenge. Furthermore, it can lead to severe complications such as gastric bleeding, elevating the risk of adverse outcomes for solid tumor patients if immunotherapy is interrupted. Therefore, gaining a thorough under-standing of the pathogenesis, clinical manifestations, diagnostic criteria, and treatment of immune-related gastritis is of utmost importance for early identification, diagnosis, and treatment. Additionally, the treatment of immune-related gastritis should be personalized according to the specific condition of each patient. For patients with grade 2-3 irAEs, restarting immune checkpoint inhibitors (ICIs) therapy may be considered when symptoms subside to grade 0-1. When restarting ICIs therapy, it is often recommended to use different types of ICIs. For grade 4 irAEs, permanent discontinuation of the medication is necessary., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2024
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8. Rodent model of metabolic dysfunction-associated fatty liver disease: a systematic review.
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Cui XS, Li HZ, Li L, Xie CZ, Gao JM, Chen YY, Zhang HY, Hao W, Fu JH, and Guo H
- Abstract
Although significant progress has been made in developing preclinical models for metabolic dysfunction-associated steatotic liver disease (MASLD), few have encapsulated the essential biological and clinical outcome elements reflective of the human condition. We conducted a comprehensive literature review of English-language original research articles published from 1990 to 2023, sourced from PubMed, Embase, and Web of Science, aiming to collate studies that provided a comparative analysis of physiological, metabolic, and hepatic histological characteristics between MASLD models and control groups. The establishment of a robust metabolic dysfunction-associated steatotic liver rodent model hinges on various factors, including animal species and strains, sex, induction agents and methodologies, and the duration of induction. Through this review, we aim to guide researchers in selecting suitable induction methods and animal species for constructing preclinical models aligned with their specific research objectives and laboratory conditions. Future studies should strive to develop simple, reliable, and reproducible models, considering the model's sensitivity to factors such as light-dark cycles, housing conditions, and environmental temperature. Additionally, the potential of diverse in vitro models, including 3D models and liver organ technology, warrants further exploration as valuable tools for unraveling the cellular mechanisms underlying fatty liver disease., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
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- 2024
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9. Transcriptome analysis of the effects of high temperature on zygotic genome activation in porcine embryos.
- Author
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Sun MH, Zhan CL, Li XH, Lee SH, and Cui XS
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- Animals, Swine, Hot Temperature, Embryonic Development genetics, Transcriptome, Genome, Embryo, Mammalian metabolism, Zygote metabolism, Gene Expression Profiling, Gene Expression Regulation, Developmental
- Abstract
Damage to the development of porcine gametes and embryos caused by high temperatures (HT) is one of the main reasons for the decline in the economic benefits of the livestock industry. Zygotic genome activation (ZGA) marks the beginning of gene expression programs in mammalian pre-implantation embryos. In pigs, ZGA occurs at the 4-cell (4 C) stage, indicating that correct gene expression at this stage plays an important regulatory role in embryonic development. However, the effect of the HT environment on early porcine embryonic development and the RNA expression profile of ZGA remain unclear. In this study, we compared the RNA transcription patterns of porcine 4 C embryos under normal and HT conditions using RNA-seq and identified 326 differentially expressed genes (DEGs). These changes were mainly related to DNA polymerase activity, DNA replication, and nucleotidyltransferase activity. In addition, entries for reverse transcription and endonuclease activity were enriched, indicating that ZGA interfered under HT conditions. Further comparison of the experimental results with the porcine ZGA gene revealed 39 ZGA genes among the DEGs. KEGG and GSEA analysis showed that the oxidative phosphorylation pathway was significantly enriched and signaling pathways related to energy metabolism were significantly downregulated. We also found that NDUFA6 and CDKN1A were located at the center of the protein-protein interaction network diagram of the DEGs. In summary, HT conditions affect mitochondrial function and oxidative phosphorylation levels, and lead to changes in the expression pattern of ZGA in early porcine embryos, with its hub genes NDUFA6 and CDKN1A., (© 2024. The Author(s).)
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- 2024
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10. Current situation and influencing fctors of oral frailty for community-dwelling older adults in the northeastern border areas of China: A cross-sectional study.
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Wang GM, Xing XY, Xia ZH, Yu WJ, Ren H, Teng MY, and Cui XS
- Abstract
Objectives: Unique lifestyle and cultural factors in China may lead to distinct patterns of risk factors for oral frailty among older adults, especially in regions inhabited by northeastern border minority groups., Methods: From July to November 2023, a convenience sampling method was employed to select older adults from three communities in Yanji City as the subjects. Data were collected by a set of questionnaires., Results: A total of 478 older adults were included, revealing a prevalence rate of 71.6 % for oral frailty. Factors influencing were found to include age, ethnicity, gender, income, number of chronic diseases, body mass index, drinking, physical frailty, sleep disorders, and attitudes towards aging (p < 0.05)., Conclusions: There is a higher prevalence of oral frailty. It is crucial to prioritize the oral health issues of older adults with high-risk factors and implement targeted intervention measures to reduce and control the occurrence and progression of oral frailty., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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11. G-Protein-Coupled Receptor Kinase 2 Inhibition Induces Meiotic Arrest by Disturbing Ca 2+ Release in Porcine Oocytes.
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Kim JD, Lee SH, Li XH, Lu QY, Zhan CL, Lee GH, Sim JM, Song HJ, Zhou D, and Cui XS
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- Animals, Female, Swine, Maturation-Promoting Factor metabolism, In Vitro Oocyte Maturation Techniques veterinary, Oocytes drug effects, Meiosis drug effects, G-Protein-Coupled Receptor Kinase 2 metabolism, Calcium metabolism
- Abstract
G-protein-coupled receptor kinase 2 (GRK2) interacts with Gβγ and Gαq, subunits of G-protein alpha, to regulate cell signalling. The second messenger inositol trisphosphate, produced by activated Gαq, promotes calcium release from the endoplasmic reticulum (ER) and regulates maturation-promoting factor (MPF) activity. This study aimed to investigate the role of GRK2 in MPF activity during the meiotic maturation of porcine oocytes. A specific inhibitor of GRK2 (βi) was used in this study. The present study showed that GRK2 inhibition increased the percentage of oocyte arrest at the metaphase I (MI) stage (control: 13.84 ± 0.95%; βi: 31.30 ± 4.18%), which resulted in the reduction of the maturation rate (control: 80.36 ± 1.94%; βi: 65.40 ± 1.14%). The level of phospho-GRK2 decreased in the treated group, suggesting that GRK2 activity was reduced upon GRK2 inhibition. Furthermore, the addition of βi decreased Ca
2+ release from the ER. The protein levels of cyclin B and cyclin-dependent kinase 1 were higher in the treatment group than those in the control group, indicating that GRK2 inhibition prevented a decrease in MPF activity. Collectively, GRK2 inhibition induced meiotic arrest at the MI stage in porcine oocytes by preventing a decrease in MPF activity, suggesting that GRK2 is essential for oocyte meiotic maturation in pigs., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)- Published
- 2024
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12. MAT2A is essential for zygotic genome activation by maintaining of histone methylation in porcine embryos.
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Li XH, Lee SH, Lu QY, Zhan CL, Lee GH, Kim JD, Sim JM, Song HJ, and Cui XS
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- Animals, Swine embryology, Gene Expression Regulation, Developmental, Embryonic Development, Methylation, Zygote metabolism, Embryo, Mammalian metabolism, Genome, Methionine Adenosyltransferase genetics, Methionine Adenosyltransferase metabolism, Histones metabolism, Histones genetics
- Abstract
Methionine adenosyltransferase 2A (MAT2A) is an essential enzyme in the methionine cycle that generates S-adenosylmethionine (SAM) by reacting with methionine and ATP. SAM acts as a methyl donors for histone and DNA methylation, which plays key roles in zygotic genome activation (ZGA). However, the effects of MAT2A on porcine ZGA remain unclear. To investigate the function of MAT2A and its underlying mechanism in porcine ZGA, MAT2A was knocked down by double-stranded RNA injection at the 1-cell stage. MAT2A is highly expressed at every stage of porcine embryo development. The percentages of four-cell-stage embryos and blastocysts were lower in the MAT2A-knockdown (KD) group than in the control group. Notably, depletion of MAT2A decreased the levels of H3K4me2, H3K9me2/3, and H3K27me3 at the four-cell stage, whereas MAT2A KD reduced the transcriptional activity of ZGA genes. MAT2A KD decreased embryonic ectoderm development (EED) and enhancer of zeste homolog 2 (EZH2) expression. Exogenous SAM supplementation rescued histone methylation levels and developmental arrest induced by MAT2A KD. Additionally, MAT2A KD significantly increased DNA damage and apoptosis. In conclusion, MAT2A is involved in regulating transcriptional activity and is essential for regulating histone methylation during porcine ZGA., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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13. GRK2 is critical for the cleavage of the porcine embryo by regulating HSP90 and the AKT pathway.
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Zhou D, Li XH, Lee SH, Kim JD, Lee GH, Sim JM, and Cui XS
- Subjects
- Animals, Swine, Female, Gene Expression Regulation, Developmental, G-Protein-Coupled Receptor Kinase 2 metabolism, G-Protein-Coupled Receptor Kinase 2 genetics, HSP90 Heat-Shock Proteins metabolism, HSP90 Heat-Shock Proteins genetics, Embryonic Development, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction
- Abstract
In Brief: GRK2 deficiency disrupts the early embryonic development in pigs. The regulation of GRK2 on HSP90 and AKT may also play an important role during embryo development and tumor formation., Abstract: Among the family of GPCR kinases (GRKs) that regulate receptor phosphorylation and signaling termination, G-protein-coupled receptor kinase 2 (GRK2) binds to HSP90 in response to hypoxia or other stresses. In this study, we investigated the effects of GRK2 knockdown and inhibition on porcine embryonic development from the zygote stage. Immunofluorescence and western blotting were used to determine the localization and expression, respectively, of GRK2 and related proteins. First, GRK2 and p-GRK2 were expressed in both the cytoplasm and membrane and co-localized with HSP90 on the membrane. The mRNA level of GRK2 increased until the 8C-morula stage, suggesting that GRK2 may play an essential role during the early development of the porcine embryos. GRK2 knockdown reduced porcine embryo development capacity and led to significantly decreased blastocyst quality. In addition, inhibition of GRK2 also induced poor ability of embryo development at an early stage, indicating that GRK2 is critical for embryonic cleavage in pigs. Knockdown and inhibition of GRK2 reduced HSP90 expression, AKT activation, and cAMP levels. Additionally, GRK2 deficiency increased LC3 expression, suggesting enhanced autophagy during embryo development. In summary, we showed that GRK2 binds to HSP90 on the membrane to regulate embryonic cleavage and AKT activation during embryonic development in pigs.
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- 2024
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14. In Vivo-Matured Oocyte Resists Post-Ovulatory Aging through the Hub Genes DDX18 and DNAJC7 in Pigs.
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Zhan CL, Zhou D, Sun MH, Jiang WJ, Lee SH, Li XH, Lu QY, Kim JD, Lee GH, Sim JM, Chung HJ, Cho ES, Sa SJ, and Cui XS
- Abstract
Assisted reproduction technology (ART) procedures are often impacted by post-ovulatory aging (POA), which can lead to reduced fertilization rates and impaired embryo development. This study used RNA sequencing analysis and experimental validation to study the similarities and differences between in vivo- and vitro-matured porcine oocytes before and after POA. Differentially expressed genes (DEGs) between fresh in vivo-matured oocyte (F_vivo) and aged in vivo-matured oocyte (A_vivo) and DEGs between fresh in vitro-matured oocyte (F_vitro) and aged in vitro-matured oocyte (A_vitro) were intersected to explore the co-effects of POA. It was found that "organelles", especially "mitochondria", were significantly enriched Gene Ontology (GO) terms. The expression of genes related to the "electron transport chain" and "cell redox homeostasis" pathways related to mitochondrial function significantly showed low expression patterns in both A_vivo and A_vitro groups. Weighted correlation network analysis was carried out to explore gene expression modules specific to A_vivo. Trait-module association analysis showed that the red modules were most associated with in vivo aging. There are 959 genes in the red module, mainly enriched in "RNA binding", "mRNA metabolic process", etc., as well as in GO terms, and "spliceosome" and "nucleotide excision repair" pathways. DNAJC7 , IK , and DDX18 were at the hub of the gene regulatory network. Subsequently, the functions of DDX18 and DNAJC7 were verified by knocking down their expression at the germinal vesicle (GV) and Metaphase II (MII) stages, respectively. Knockdown at the GV stage caused cell cycle disorders and increase the rate of abnormal spindle. Knockdown at the MII stage resulted in the inefficiency of the antioxidant melatonin, increasing the level of intracellular oxidative stress, and in mitochondrial dysfunction. In summary, POA affects the organelle function of oocytes. A_vivo oocytes have some unique gene expression patterns. These genes may be potential anti-aging targets. This study provides a better understanding of the detailed mechanism of POA and potential strategies for improving the success rates of assisted reproductive technologies in pigs and other mammalian species.
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- 2024
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15. The Effect of Inhibiting the Wingless/Integrated (WNT) Signaling Pathway on the Early Embryonic Disc Cell Culture in Chickens.
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Ren W, Zheng D, Liu G, Wu G, Peng Y, Wu J, Jin K, Zuo Q, Zhang Y, Li G, Han W, Cui XS, Chen G, Li B, and Niu YJ
- Abstract
The utilization of chicken embryonic-derived pluripotent stem cell (PSC) lines is crucial in various fields, including growth and development, vaccine and protein production, and germplasm resource protection. However, the research foundation for chicken PSCs is relatively weak, and there are still challenges in establishing a stable and efficient PSC culture system. Therefore, this study aims to investigate the effects of the FGF2/ERK and WNT/β-catenin signaling pathways, as well as different feeder layers, on the derivation and maintenance of chicken embryonic-derived PSCs. The results of this study demonstrate that the use of STO cells as feeder layers, along with the addition of FGF2, IWR-1, and XAV-939 (FIX), allows for the efficient derivation of chicken PSC-like cells. Under the FIX culture conditions, chicken PSCs express key pluripotency genes, such as POUV , SOX2 , and NANOG , as well as specific proteins SSEA-1, C-KIT, and SOX2, indicating their pluripotent nature. Additionally, the embryoid body experiment confirms that these PSC-like cells can differentiate into cells of three germ layers in vitro, highlighting their potential for multilineage differentiation. Furthermore, this study reveals that chicken Eyal-Giladi and Kochav stage X blastodermal cells express genes related to the primed state of PSCs, and the FIX culture system established in this research maintains the expression of these genes in vitro. These findings contribute significantly to the understanding and optimization of chicken PSC culture conditions and provide a foundation for further exploration of the biomedical research and biotechnological applications of chicken PSCs.
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- 2024
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16. Nobiletin enhances mitochondrial function by regulating SIRT1/PGC-1α signaling in porcine oocytes during in vitro maturation.
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Lee SH, Li XH, Lu QY, Zhan CL, Kim JD, Lee GH, Sim JM, and Cui XS
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- Animals, Swine, Signal Transduction, Oocytes metabolism, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism, Sirtuin 1 metabolism, Mitochondria metabolism, Flavones
- Abstract
Nobiletin is a natural flavonoid found in citrus fruits with beneficial effects, including anti-inflammatory, anti-cancer and anti-oxidation effects. The aim of this study was to investigate whether nobiletin improves mitochondrial function in porcine oocytes and examine the underlying mechanism. Oocytes enclosed by cumulus cells were cultured in TCM-199 for 44 h with 0.1% dimethyl sulfoxide (control), or supplemented with 5, 10, 25, and 50 μM of nobiletin (Nob5, Nob10, Nob25, and Nob50, respectively). Oocyte maturation rate was significantly enhanced in Nob10 (70.26 ± 0.45%) compared to the other groups (control: 60.12 ± 0.47%; Nob5: 59.44 ± 1.63%; Nob25: 63.15 ± 1.38%; Nob50: 46.57 ± 1.19%). The addition of nobiletin reduced the levels of reactive oxygen species and increased glutathione levels. Moreover, Nob10 promoted mitochondrial biogenesis by upregulating the protein levels of sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α). This resulted in an increase in the number of active mitochondria, mitochondrial DNA copy number, mitochondrial membrane potential, and ATP production, thereby enhancing mitochondrial function. The protein level of p53 decreased, followed by the phosphorylation of B-cell lymphoma 2, suggesting a reduction in mitochondria-mediated apoptosis in the Nob10 group. Additionally, the release of cytochrome c from the mitochondria was significantly diminished along with a decrease in the protein expression of caspase 3. Thus, nobiletin has a great potential to promote the in vitro maturation of porcine oocytes by suppressing oxidative stress and promoting mitochondrial function through the upregulation of the SIRT1/PGC-1α signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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17. Clonally derived chicken primordial germ cell lines maintain biological characteristics and proliferative potential in long-term culture.
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Niu YJ, Ren W, Liu G, Jin K, Zheng D, Zuo Q, Zhang Y, Cui XS, Chen G, and Li B
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- Animals, Male, Female, Cell Line, Cells, Cultured, Proto-Oncogene Proteins c-kit metabolism, Chickens genetics, Germ Cells metabolism
- Abstract
Chicken primordial germ cells (PGCs) are important cells with significant implications in preserving genetic resources, chicken breeding and production, and basic research on genetics and development. Currently, chicken PGCs can be cultured long-term in vitro to produce single-cell clones. However, systematic exploration of the cellular characteristics of these single-cell clonal lines has yet to be conducted. In this study, single-cell clonal lines were established from male and female PGCs of Rugao Yellow Chicken and Shouguang Black Chicken, respectively, using a micropipette-based method for single-cell isolation and culture. Analysis of glycogen granule staining, mRNA expression of pluripotency marker genes (POUV, SOX2, NANOG), germ cell marker genes (DAZL, CVH), and SSEA-1, EMA-1, SOX2, C-KIT, and CVH protein expression showed positive results, indicating that PGCs maintain normal cellular properties after single-cell cloning. Furthermore, tests on proliferation ability and gene expression levels in PGC single-cell clonal lines showed high expression of the pluripotency-related genes and TERT compared to control PGCs, and PGC single-cell clonal lines demonstrated higher proliferation ability. Finally, green fluorescent protein (GFP)-PGC single-cell clonal lines were established, and it was found that these single-cell clonal lines could still migrate into the gonads of recipients, suggesting their potential for germ-line transmission. This study systematically validated the normal cellular characteristics of PGC single-cell clonal lines, indicating that they could be applied in genetic modification research on chickens., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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18. Supplementation with Eupatilin during In Vitro Maturation Improves Porcine Oocyte Developmental Competence by Regulating Oxidative Stress and Endoplasmic Reticulum Stress.
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Wang J, Li YH, Liu RP, Wang XQ, Zhu MB, Cui XS, Dai Z, Kim NH, and Xu YN
- Abstract
Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is a flavonoid derived from Artemisia plants that has beneficial biological activities, such as anti-apoptotic, anti-oxidant, and anti-inflammatory activities. However, the protective effects of eupatilin against oxidative stress and endoplasmic reticulum stress in porcine oocyte maturation are still unclear. To investigate the effect of eupatilin on the development of porcine oocytes after in vitro maturation and parthenogenetic activation, we added different concentrations of eupatilin in the process of porcine oocyte maturation in vitro, and finally selected the optimal concentration following multiple comparisons and analysis of test results using SPSS (version 17.0; IBM, Chicago, IL, USA) software. The results showed that 0.1 μM eupatilin supplementation did not affect the expansion of porcine cumulus cells, but significantly increased the extrusion rate of porcine oocyte polar bodies, the subsequent blastocyst formation rate, and the quality of parthenogenetically activated porcine embryos. Additionally, it reduced the level of reactive oxygen species in cells and increased glutathione production. Further analysis revealed that eupatilin supplementation could reduce apoptosis, DNA double-strand breaks, and endoplasmic reticulum stress. In conclusion, supplementation with 0.1 μM eupatilin during in vitro maturation improved oocyte maturation and subsequent embryo development by reducing oxidative stress and endoplasmic reticulum stress.
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- 2024
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19. Design, Synthesis, and Biochemical Analysis of a Molecule Designed to Enhance Endosomal Escape.
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Jadhav SG, Setten RL, Medina C, Cui XS, and Dowdy SF
- Subjects
- Humans, Proteins metabolism, RNA, Small Interfering metabolism, Cell Membrane, Endosomes metabolism, Endocytosis
- Abstract
RNA therapeutics, including siRNAs, ASOs, and PMOs, have great potential to treat human disease. However, RNA therapeutics are too large, too charged, and/or too hydrophilic to cross the cellular membrane and are instead taken up into cells by endocytosis. Unfortunately, the vast majority of RNA therapeutics remain trapped inside endosomes (≥ 99%), which is the sole reason preventing their use to treat cancer, COVID, and other diseases. In contrast, enveloped viruses, such as influenza, also have an endosomal escape problem, but have evolved a highly efficient endosomal escape mechanism using trimeric hemagglutinin (HA) fusogenic protein. HA contains an outer hydrophilic domain (HA1) that masks an inner hydrophobic fusogenic/endosomal escape domain (HA2). Once inside endosomes, HA1 is shed to expose HA2 that, due to hydrophobicity, buries itself into the endosomal lipid bilayer, driving escape into the cytoplasm in a non-toxic fashion. To begin to address the RNA therapeutics rate-limiting endosomal escape problem, we report here a first step in the design and synthesis of a universal endosomal escape domain (uEED) that biomimics the enveloped virus escape mechanism. uEED contains an outer hydrophilic mask covalently attached to an inner hydrophobic escape domain. In plasma, uEED is inert and highly metabolically stable; however, when placed in endo/lysosomal conditions, uEED is activated by enzymatic removal of the hydrophilic mask, followed by self-immolation of the linker resulting in exposure of the hydrophobic indole ring domain in the absence of any hydrophilic tags. Thus, uEED is a synthetic biomimetic of the highly efficient viral endosomal escape mechanism., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)
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- 2023
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20. High Temperature-Induced m6A Epigenetic Changes Affect Early Porcine Embryonic Developmental Competence in Pigs.
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Sun MH, Jiang WJ, Li XH, Lee SH, Heo G, Zhou D, Guo J, and Cui XS
- Subjects
- Animals, Swine, Temperature, Mammals, Epigenesis, Genetic, Embryonic Development
- Abstract
N6-methyladenosine (m6A), the most prevalent modification in eukaryotic messenger RNA (mRNA), plays a key role in various developmental processes in mammals. Three proteins that affect RNA m6A modification have been identified: methyltransferases, demethylases, and m6A-binding proteins, known as "writer," "eraser," and "reader" proteins, respectively. However, changes in the m6A modification when early porcine embryos are exposed to stress remain unclear. In this study, we exposed porcine oocytes to a high temperature (HT, 41°C) for 10 h, after which the mature oocytes were parthenogenetically activated and cultured for 7 days to the blastocyst stage. HT significantly decreased the rates of the first polar body extrusion and blastocyst formation. Further detection of m6A modification found that HT can lead to increased expression levels of "reader," YTHDF2, and "writer," METTL3, and decreased expression levels of "eraser," FTO, resulting in an increased level of m6A modification in the embryos. Additionally, heat shock protein 70 (HSP70) is upregulated under HT conditions. Our study demonstrated that HT exposure alters m6A modification levels, which further affects early porcine embryonic development., Competing Interests: Conflict of Interest The authors declare that they have no competing interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Microscopy Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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21. Effectiveness of nurse-led multidisciplinary interventions in primary health care: A systematic review and meta-analysis.
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Lei YY, Ya SRT, Zheng YR, and Cui XS
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- Humans, Anxiety therapy, Anxiety Disorders, Primary Health Care, Quality of Life, Nurse's Role
- Abstract
Aim: This review aimed to synthesize the available evidence on the effectiveness of nurse-led multidisciplinary interventions in primary health care., Methods: The following Chinese and English databases were searched for relevant articles: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang and Chinese Biomedical Literature Database (CBM), from the establishment of the databases until the last updating search 1 April 2022. Two researchers screened the studies independently and extracted the data. Meta-analysis was performed using the RevMan 5.3 software., Results: A total of 12 studies were included in this review. It was found that nurse-led multidisciplinary interventions significantly shortened patients' length of stay in hospital (standardized mean differences [SMD] = -1.28, 95%CI: -2.03 to -0.54; P<0.001) and decreased incidences of complications (RR = 0.24, 95%CI:0.10 to 0.54; P = 0.0006) compared to the control group, and lowered patients' anxiety levels (SMD = -1.21, 95%CI: -1.99 to -0.44; P<0.01) and depression levels (SMD = -1.85, 95%CI: -3.42 to -0.28; P<0.0001). Furthermore, the results of subgroup analysis indicated that nurse-led multidisciplinary interventions had significant effects on patients' self-management ability (SMD = 4.45, 95%CI:2.45 to 6.44; P<0.0001) and quality of life (SMD = 1.01, 95%CI: 0.63 to 1.40; P<0.0001) compared to the control group., Conclusions: Nurse-led multidisciplinary interventions had strong effects in primary health care, contributing to shorten patients' length of stay in hospital, decrease incidences of complications and reduce the levels of anxiety and depression. Moreover, nurse-led multidisciplinary interventions also improved patients' self-management ability and quality of life., (© 2023 John Wiley & Sons Australia, Ltd.)
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- 2023
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22. GRP78 acts as a cAMP/PKA signaling modulator through the MC4R pathway in porcine embryonic development.
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Heo G, Lee SH, Kim JD, Lee GH, Sim JM, Zhou D, Guo J, and Cui XS
- Subjects
- Female, Pregnancy, Swine, Animals, Embryonic Development, Parthenogenesis, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, GTP-Binding Proteins, Receptor, Melanocortin, Type 4, Endoplasmic Reticulum Chaperone BiP
- Abstract
Glucose-regulated protein 78 (GRP78) binds to and stabilizes melanocortin 4 receptor (MC4R), which activates protein kinase A (PKA) by regulating G proteins. GRP78 is primarily used as a marker for endoplasmic reticulum stress; however, its other functions have not been well studied. Therefore, in this study, we aimed to investigate the function of GRP78 during porcine embryonic development. The developmental quality of porcine embryos, expression of cell cycle proteins, and function of mitochondria were evaluated by inhibiting the function of GRP78. Porcine oocytes were activated to undergo parthenogenesis, and blastocysts were obtained after 7 days of in vitro culture. GRP78 function was inhibited by adding 20 μM HA15 to the in vitro culture medium. The inhibition in GRP78 function led to a decrease in G proteins release, which subsequently downregulated the cyclic adenosine monophosphate (cAMP)/PKA pathway. Ultimately, inhibition of GRP78 function induced the inhibition of CDK1 and cyclin B expression and disruption of the cell cycle. In addition, inhibition of GRP78 function regulated DRP1 and SIRT1 expression, resulting in mitochondrial dysfunction. This study provides new insights into the role of GRP78 in porcine embryonic development, particularly its involvement in the regulation of the MC4R pathway and downstream cAMP/PKA signaling. The results suggest that the inhibition of GRP78 function in porcine embryos by HA15 treatment may have negative effects on embryo quality and development. This study also demonstrated that GRP78 plays a crucial role in the functioning of MC4R, which releases the G protein during porcine embryonic development., (© 2023 Federation of American Societies for Experimental Biology.)
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- 2023
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23. Life-space mobility among community-dwelling older persons: A scoping review.
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Wang GM, Teng MY, Yu WJ, Ren H, and Cui XS
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- Humans, Aged, Aged, 80 and over, Independent Living, Mobility Limitation
- Abstract
To describe and analyze the current research status of life-space mobility of the older persons in community. The literature in PubMed, Web of Science, Cochrane Library, Embase, EBSCOhost, Scopus, OpenGrey, SinoMed, CNKI, WanFang, and VIP databases was computer searched, and the time frame was build to May 23, 2023. A total of 42 literatures were included, including 35 in English and 7 in Chinese, 30 of which were cross-sectional studies. Theoretical models related to spatial mobility included the "concentric circles" model and the "cone" model. 33 literatures reported the prevalence or level of spatial mobility limitations, and 9 assessment instruments were used, The influencing factors can be divided into four categories. 9 literatures reported on the adverse effects, and 9 literatures reported on the prevention and intervention. The limitation of life-space mobility is a common and under-recognized phenomenon among the older persons in the community,with serious adverse effects, complex and diverse influencing factors., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2023
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24. Knockdown of Y-box binding protein 1 induces autophagy in early porcine embryos.
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Jiang WJ, Lee SH, Heo G, Chung HJ, Cho ES, Sa SJ, Hochi S, and Cui XS
- Abstract
Y-box binding protein 1 ( YBX1 ) plays important roles in RNA stabilization, translation, transcriptional regulation, and mitophagy. However, its effects on porcine preimplantation embryos remain unclear. In this study, we knocked down YBX1 in the one-cell (1C) stage embryo via small interfering RNA microinjection to determine its function in porcine embryo development. The mRNA level of YBX1 was found to be highly expressed at the four-cell (4C) stage in porcine embryos compared with one-cell (1C) and two-cell (2C) stages. The number of blastocysts was reduced following YBX1 knockdown. Notably, YBX1 knockdown decreased the phosphatase and tensin homolog-induced kinase 1 ( PINK1 ) and parkin RBR E3 ubiquitin protein ligase ( PRKN ) mRNA levels. YBX1 knockdown also decreased PINK1, active mitochondria, and sirtuin 1 levels, indicating reduced mitophagy and mitochondrial biogenesis. Furthermore, YBX1 knockdown increased the levels of glucose-regulated protein 78 (GRP78) and calnexin, leading to endoplasmic reticulum (ER) stress. Additionally, YBX1 knockdown increased autophagy and apoptosis. In conclusion, knockdown of YBX1 decreases mitochondrial function, while increasing ER stress and autophagy during embryonic development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiang, Lee, Heo, Chung, Cho, Sa, Hochi and Cui.)
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- 2023
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25. ATF6 aggravates apoptosis in early porcine embryonic development by regulating organelle homeostasis under high-temperature conditions.
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Sun MH, Jiang WJ, Li XH, Lee SH, Heo G, Zhou D, Chen Z, and Cui XS
- Subjects
- Animals, Swine, Temperature, Apoptosis, Homeostasis, Embryonic Development, Activating Transcription Factor 6 genetics, Activating Transcription Factor 6 metabolism, Endoplasmic Reticulum metabolism
- Abstract
Activating transcription factor 6 (ATF6), one of the three sensor proteins in the endoplasmic reticulum (ER), is an important regulator of ER stress-induced apoptosis. ATF6 resides in the ER and, upon activation, is translocated to the Golgi apparatus, where it is cleaved by site-1 protease (S1P) to generate an amino-terminal cytoplasmic fragment. Although recent studies have made progress in elucidating the regulatory mechanisms of ATF6, its function during early porcine embryonic development under high-temperature (HT) stress remains unclear. In this study, zygotes were divided into four groups: control, HT, HT+ATF6 knockdown, and HT+PF (S1P inhibitor). Results showed that HT exposure induced ER stress, which increased ATF6 protein expression and led to a decrease in the blastocyst rate. Next, ATF6 expression was knocked down in HT embryos under microinjection of ATF6 double-stranded RNA (dsRNA). Results revealed that ATF6 knockdown (ATF6-KD) attenuated the increased expression of CHOP, an ER stress marker, and Ca
2+ release induced by HT. In addition, ATF6-KD alleviated homeostasis dysregulation among organelles caused by HT-induced ER stress, and further reduced Golgi apparatus and mitochondrial dysfunction in HT embryos. AIFM2 is an important downstream effector of ATF6. Results showed that ATF6-KD reduced the occurrence of AIFM2-mediated embryonic apoptosis at HT. Taken together, our findings suggest that ATF6 is a crucial mediator of apoptosis during early porcine embryonic development, resulting from HT-induced ER stress and disruption of organelle homeostasis.- Published
- 2023
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26. Effects of nursing intervention based on a positive motivational model on cardiac function, self-management and quality of life in elderly patients with coronary heart disease.
- Author
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Tuo Ya SR, Lei YY, Bao LX, and Cui XS
- Subjects
- Aged, Humans, Motivation, Quality of Life, Stroke Volume, Ventricular Function, Left, Self-Management, Coronary Disease therapy
- Abstract
Objective: The aim of this study was to analyze the effects of nursing intervention based on a positive motivational model on cardiac function, self-management, and life quality in elderly patients with coronary heart disease (CHD)., Patients and Methods: A total of 112 elderly CHD patients were picked as the subjects of this research from August 2021 to August 2022. All patients were randomized to the observation group and regular group by a two-color sampling method, with 56 cases in each group. Subjects in the regular group and observation group received traditional interventions and additional positive motivational model nursing interventions, respectively. The cardiac function [left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD)], sports endurance, self-management ability, psychological status [depression self-assessment scale (SDS), anxiety self-assessment scale (SAS)], and life quality before and after the intervention were compared between two groups. The readiness for discharge scores and satisfaction with nursing care were compared between the two groups after the intervention., Results: After the intervention, the LVEF levels of the patients in both groups were elevated, and the LVESD and LVEDD levels were sharply decreased (p < 0.05). The improvement in cardiac function indexes was more evident in the observation group than in the regular group (p < 0.001). The readiness for discharge score of patients was markedly higher in the observation group than in the regular group (p < 0.01). After the intervention, the self-management score and sports endurance score of patients in both groups were evidently elevated (p < 0.05), which were much higher in the observation group than in the control (p < 0.001). The nursing satisfaction of patients in the observation group was 92.86%, much higher than 73.21% in the regular group (p < 0.05). The observation group had much lower SDS and SAS scores than the regular group after the intervention (p < 0.001). After the intervention, the observation group had a much higher life quality score than the regular group (p < 0.001)., Conclusions: The nursing intervention model based on the positive motivation model could significantly improve the cardiac function, discharge readiness, sports endurance, and self-management behavior of elderly patients with CHD, thereby improving their quality of life and achieving higher patient satisfaction.
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- 2023
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27. ZSCAN4 Regulates Zygotic Genome Activation and Telomere Elongation in Porcine Parthenogenetic Embryos.
- Author
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Li XH, Sun MH, Jiang WJ, Zhou D, Lee SH, Heo G, Chen Z, and Cui XS
- Subjects
- Animals, Mice, Swine, Telomere Shortening, DNA-Binding Proteins metabolism, Zygote metabolism, Embryonic Development genetics, Gene Expression Regulation, Developmental, Transcription Factors genetics, Transcription Factors metabolism, Telomere genetics, Telomere metabolism
- Abstract
Zinc finger and SCAN domain-containing 4 ( ZSCAN4 ), a DNA-binding protein, maintains telomere length and plays a key role in critical aspects of mouse embryonic stem cells, including maintaining genomic stability and defying cellular senescence. However, the effect of ZSCAN4 in porcine parthenogenetic embryos remains unclear. To investigate the function of ZSCAN4 and the underlying mechanism in porcine embryo development, ZSCAN4 was knocked down via dsRNA injection in the one-cell stage. ZSCAN4 was highly expressed in the four- and five- to eight-cell stages in porcine embryos. The percentage of four-cell stage embryos, five- to eight-cell stage embryos, and blastocysts was lower in the ZSCAN4 knockdown group than in the control group. Notably, depletion of ZSCAN4 induced the protein expression of DNMT1 and 5-Methylcytosine (5mC, a methylated form of the DNA base cytosine) in the four-cell stage. The H3K27ac level and ZGA genes expression decreased following ZSCAN4 knockdown. Furthermore, ZSCAN4 knockdown led to DNA damage and shortened telomere compared with the control. Additionally, DNMT1 -dsRNA was injected to reduce DNA hypermethylation in ZSCAN4 knockdown embryos. DNMT1 knockdown rescued telomere shortening and developmental defects caused by ZSCAN4 knockdown. In conclusion, ZSCAN4 is involved in the regulation of transcriptional activity and is essential for maintaining telomere length by regulating DNMT1 expression in porcine ZGA.
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- 2023
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28. Y-box binding protein 1 influences zygotic genome activation by regulating N6-methyladenosine in porcine embryos.
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Jiang WJ, Sun MH, Li XH, Lee SH, Heo G, Zhou D, and Cui XS
- Subjects
- Animals, Adenosine metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Swine, Embryonic Development, Zygote metabolism, DNA-Binding Proteins metabolism
- Abstract
Y-box binding protein 1 (YBX1) is a member of the family of DNA- and RNA-binding proteins that play crucial roles in multiple aspects, including RNA stabilization, translational repression, and transcriptional regulation; however, its roles in embryo development remain less known. In this study, to investigate the function of YBX1 and its mechanism of action in porcine embryo development, YBX1 was knocked down by microinjecting YBX1 siRNA at the one-cell stage. YBX1 is located in the cytoplasm during embryonic development. The mRNA level of YBX1 was increased from the four-cell stage to the blastocyst stage but was significantly decreased in YBX1 knockdown embryos compared with the control. Moreover, the percentage of blastocysts was decreased following YBX1 knockdown compared with the control. Defecting YBX1 expression increased maternal gene mRNA expression and decreased zygotic genome activation (ZGA) gene mRNA expression and histone modification owing to decreased levels of N6-methyladenosine (m6A) writer N6-adenosine-methyltransferase 70 kDa subunit (METTL3) and reader insulin-like growth factor 2 mRNA-binding protein (IGF2BP1). In addition, IGF2BP1 knockdown showed that YBX1 regulated the ZGA process through m6A modification. In conclusion, YBX1 is essential for early embryo development because it regulates the ZGA process., (© 2023 Wiley Periodicals LLC.)
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- 2023
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29. Involvement of Rictor/mTORC2/Akt/GLUT4 pathway in the regulation of energy metabolism in the gastric smooth muscle of diabetic rats.
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Yan S, Zheng YR, Jin Z, Zhang MH, and Cui XS
- Subjects
- Rats, Animals, Mechanistic Target of Rapamycin Complex 2 metabolism, TOR Serine-Threonine Kinases metabolism, Energy Metabolism, Phosphorylation, Muscle, Smooth metabolism, Adenosine Triphosphate metabolism, Proto-Oncogene Proteins c-akt metabolism, Diabetes Mellitus, Experimental metabolism
- Abstract
Diabetes mellitus can be accompanied by a variety of complications. The purpose of the present study was to characterize the Rictor/mTOR complex 2 (mTORC2)/Akt/glucose transporter 4 (GLUT4) pathway and its effects on energy metabolism in the gastric smooth muscle of diabetic rats. Diabetes was induced in rats using streptozotocin and their phenotype was compared with untreated rats. The relationship between gastric motility and energy metabolism was analyzed by comparing the contraction and ATP metabolism of muscle strips. Western blotting was used to detect the expression of key proteins in the pathway. The diabetic rats demonstrated less frequent and less powerful gastric smooth muscle contractions. The concentrations of ADP, AMP, and ATP, and the energy charge in gastric smooth muscle changed in different periods of diabetes, and these changes were consistent with changes in mechanistic target of rapamycin (mTOR) protein content. The expression of the key intermediates in signal transduction in the Rictor/mTORC2/Akt/GLUT4 pathway also underwent significant changes. Rictor protein expression increased during the development of diabetes, but the activation of mTORC2 did not increase with the increase in Rictor expression. GLUT4 translocation is regulated by Akt and its expression change during the development of diabetes. These findings suggest that altered energy metabolism is present in gastric smooth muscle that is associated with changes in the Rictor/mTORC2/Akt/GLUT4 pathway. Rictor/mTORC2/Akt/GLUT4 pathway may be involved in the regulation of energy metabolism in the gastric smooth muscle of diabetic rats and the development of diabetic gastroparesis.
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- 2023
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30. Oviduct epithelial cell‑derived extracellular vesicles promote the developmental competence of IVF porcine embryos.
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Fang X, Bang S, Tanga BM, Seo C, Zhou D, Seong G, Saadeldin IM, Lee S, Cui XS, and Cho J
- Subjects
- Humans, Female, Male, Animals, Swine, Oviducts, Oocytes, Embryonic Development, Spermatozoa, Semen, Fertilization in Vitro
- Abstract
Assisted reproductive technology has increased the efficiency of animal reproduction. However, polyspermy is a significant limitation of porcine in vitro fertilization (IVF). Therefore, reducing the polyspermy rate and improving monospermic embryos is crucial. Recent studies have reported that oviductal fluid, along with its contents of extracellular vesicles (EVs), enhanced the fertilization process and supported embryo development. Consequently, the present study investigated the effects of porcine oviduct epithelial cells (OEC‑EVs) on sperm‑oocyte interactions during porcine IVF and evaluated in vitro embryo developmental competence outcomes. During IVF embryo development, the cleavage rate was significantly higher in the group treated with 50 ng/ml OEC‑EVs compared with the control group (67.6±2.5 vs. 57.3±1.9; P<0.05). Furthermore, the OEC‑EV group had significantly more embryos (16.4±1.2 vs. 10.2±0.8; P<0.05), and the polyspermy rate significantly decreased (32.9±2.5 vs. 43.8±3.1; P<0.05) compared with that of the control group. Additionally, the fluorescence intensities of cortical granules (3.56±0.47 vs. 2.15±0.24; P<0.05) and active mitochondria (8.14±0.34 vs. 5.96±0.38; P<0.05) were significantly higher in the OEC‑EV group compared with those in the control group. In conclusion, OEC‑EV adsorption and penetration crosstalk between sperm and oocytes was observed. OEC‑EV treatment was demonstrated to significantly improve the concentration and distribution of cortical granules in oocytes. Furthermore, OEC‑EVs also increased oocyte mitochondrial activity, reduced polyspermy and increased the IVF success rate.
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- 2023
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31. Alpha-lipoic acid attenuates heat stress-induced apoptosis via upregulating the heat shock response in porcine parthenotes.
- Author
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Lee SH, Sun MH, Jiang WJ, Li XH, Heo G, Zhou D, Chen Z, and Cui XS
- Subjects
- Animals, Antioxidants pharmacology, Apoptosis, Blastocyst, Heat-Shock Response, Swine, Heat Stress Disorders, Thioctic Acid pharmacology
- Abstract
Heat stress (HS) is a long-standing hurdle that animals face in the living environment. Alpha-lipoic acid (ALA) is a strong antioxidant synthesized by plants and animals. The present study evaluated the mechanism of ALA action in HS-induced early porcine parthenotes development. Parthenogenetically activated porcine oocytes were divided into three groups: control, high temperature (HT) (42 °C for 10 h), and HT + ALA (with 10 µM ALA). The results show that HT treatment significantly reduced the blastocyst formation rate compared to the control. The addition of ALA partially restored the development and improved the quality of blastocysts. Moreover, supplementation with ALA not only induced lower levels of reactive oxygen species and higher glutathione levels but also markedly reduced the expression of glucose regulatory protein 78. The protein levels of heat shock factor 1 and heat shock protein 40 were higher in the HT + ALA group, which suggests activation of the heat shock response. The addition of ALA reduced the expression of caspase 3 and increased the expression of B-cell lymphoma-extra-large protein. Collectively, this study revealed that ALA supplementation ameliorated HS-induced apoptosis by suppressing oxidative and endoplasmic reticulum stresses via activating the heat shock response, which improved the quality of HS-exposed porcine parthenotes., (© 2023. The Author(s).)
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- 2023
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32. Knock-down of YME1L1 induces mitochondrial dysfunction during early porcine embryonic development.
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Zhou D, Sun MH, Jiang WJ, Li XH, Lee SH, Heo G, Choi J, Kim KS, and Cui XS
- Abstract
YME1L1, a mitochondrial metalloproteinase, is an Adenosine triphosphate (ATP)-dependent metalloproteinase and locates in the mitochondrial inner membrane. The protease domain of YME1L1 is oriented towards the mitochondrial intermembrane space, which modulates the mitochondrial GTPase optic atrophy type 1 (OPA1) processing. However, during embryonic development, there is no report yet about the role of YME1L1 on mitochondrial biogenesis and function in pigs. In the current study, the mRNA level of YME1L1 was knocked down by double strand RNA microinjection to the 1-cell stage embryos. The expression patterns of YME1L1 and its related proteins were performed by immunofluorescence and western blotting. To access the biological function of YME1L1, we first counted the preimplantation development rate, diameter, and total cell number of blastocyst on day-7. First, the localization of endogenous YME1L1 was found in the punctate structures of the mitochondria, and the expression level of YME1L1 is highly expressed from the 4-cell stage. Following significant knock-down of YME1L1, blastocyst rate and quality were decreased, and mitochondrial fragmentation was induced. YME1L1 knockdown induced excessive ROS production, lower mitochondrial membrane potential, and lower ATP levels. The OPA1 cleavage induced by YME1L1 knockdown was prevented by double knock-down of YME1L1 and OMA1. Moreover, cytochrome c , a pro-apoptotic signal, was released from the mitochondria after the knock-down of YME1L1. Taken together, these results indicate that YME1L1 is essential for regulating mitochondrial fission, function, and apoptosis during porcine embryo preimplantation development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Sun, Jiang, Li, Lee, Heo, Choi, Kim and Cui.)
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- 2023
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33. ATF7-dependent epigenetic changes induced by high temperature during early porcine embryonic development.
- Author
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Sun MH, Jiang WJ, Li XH, Lee SH, Heo G, Zhou D, Choi JS, Kim KS, Lv W, and Cui XS
- Subjects
- Animals, Swine, Heterochromatin, Temperature, Epigenesis, Genetic, Chromosomal Proteins, Non-Histone metabolism, Histones metabolism, Activating Transcription Factors genetics, Activating Transcription Factors metabolism
- Abstract
Background: Activating transcription factor 7 (ATF7) is a member of the ATF/cAMP response element (CRE) B superfamily. ATF2, ATF7, and CRE-BPa are present in vertebrates. Drosophila and fission yeast have only one homologue: dATF2 and Atf1, respectively. Under normal conditions, ATF7 promotes heterochromatin formation by recruiting histone H3K9 di- and tri-methyltransferases. Once the situation changes, all members are phosphorylated by the stress-activated kinase P38 in response to various stressors. However, the role of ATF7 in early porcine embryonic development remains unclear., Results: In this study, we found that ATF7 gradually accumulated in the nucleus and then localized on the pericentric heterochromatin after the late 4-cell stage, while being co-localized with heterochromatin protein 1 (HP1). Knockdown of ATF7 resulted in decreases in the blastocyst rate and blastocyst cell number. ATF7 depletion resulted in downregulation of HP1 and histone 3 lysine 9 dimethylation (H3K9me2) expression. These effects were alleviated when P38 activity was inhibited. High temperatures increased the expression level of pP38, while reducing the quality of porcine embryos, and led to ATF7 phosphorylation. The expression level of H3K9me2 and HP1 was decreased and regulated by P38 activity., Conclusion: Stress-induced ATF7-dependent epigenetic changes play important roles in early porcine embryonic development., (© 2022 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)
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- 2023
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34. E2F4 regulates cell cycle to mediate embryonic development in pigs.
- Author
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Jiang WJ, Sun MH, Li XH, Lee SH, Heo G, Zhou D, and Cui XS
- Subjects
- Swine, Animals, Cell Cycle, Mammals, Embryonic Development
- Abstract
In mammals, E2 factor (E2F) acts as a cell cycle regulator. E2F transcription factor 4 (E2F4) is a member of the E2F family of transcription factors and usually represents predominant E2F activity in cells. The E2F4 gene has been extensively studied in animals and is associated with multiple functions, such as cell cycle regulation and apoptosis; however, little is known about its role during embryonic development. In this study, we investigated the function of E2F4 and its mechanism of action in porcine embryo development. For this purpose, we knocked down E2F4 by microinjecting double-stranded RNA of E2F4 at the 1-cell stage. The results showed that E2F4 knockdown in porcine embryos led to a significant decrease in the blastocyst rate and total cell number. Defective E2F4 expression reduced the level of G1/S checkpoints (cyclin E-cyclin-dependent kinase 2) and cell cycle-related gene expression at the 4-cell embryo stage and blastocyst. Moreover, a decrease in E2F4 expression increased phosphorylated H2A.X variant histones and activated ataxia telangiectasia mutated (ATM) and p53-p21 pathway. In addition, E2F4 depletion caused a significant decrease in histone acetylation. Taken together, E2F4 plays a critical role as a transcriptional activator in the development of porcine embryos, an observation that contradicts its well-established role as a transcription repressor., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2023
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35. Lactoferrin: A glycoprotein that plays an active role in human health.
- Author
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Cao X, Ren Y, Lu Q, Wang K, Wu Y, Wang Y, Zhang Y, Cui XS, Yang Z, and Chen Z
- Abstract
Lactoferrin (Lf), existing widely in human and mammalian milk, is a multifunctional glycoprotein with many functions, such as immune regulation, anti-inflammation, antibacterial, antiviral, and antioxidant. These extensive functions largely attribute to its ability to chelate iron and interfere with the cellular receptors of pathogenic microorganisms and their hosts. Moreover, it is non-toxic and has good compatibility with other supplements. Thus, Lf has been widely used in food nutrition, drug carriers, biotechnology, and feed development. Although Lf has been continuously explored and studied, a more comprehensive and systematic compendium is still required. This review presents the recent advances in the structure and physicochemical properties of Lf as well as clinical studies on human diseases, with the aim of providing a reference for further research of Lf and the development of its related functional products., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cao, Ren, Lu, Wang, Wu, Wang, Zhang, Cui, Yang and Chen.)
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- 2023
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36. Rotenone causes mitochondrial dysfunction and prevents maturation in porcine oocytes.
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Heo G, Sun MH, Jiang WJ, Li XH, Lee SH, Guo J, Zhou D, and Cui XS
- Subjects
- Swine, Animals, Female, Reactive Oxygen Species, Cumulus Cells, Mitochondria, Rotenone pharmacology, Oocytes
- Abstract
Rotenone is a commonly used insecticidal chemical in agriculture and it is an inhibitor of mitochondrial complex Ⅰ. Previous studies have found that rotenone induces the production of reactive oxygen species (ROS) by inhibiting electron transport in the mitochondria of somatic and germ cells. However, there is little precise information on the effects of rotenone exposure in porcine oocytes during in vitro maturation, and the mechanisms underlying these effects have not been determined. The Cumulus-oocyte complexes were supplemented with different concentrations of rotenone to elucidate the effects of rotenone exposure on the meiotic maturation of porcine oocytes during in vitro maturation for about 48 hours. First, we found that the maturation rate and expansion of cumulus cells were significantly reduced in the 3 and 5 μM rotenone-treated groups. Subsequently, the concentration of rotenone was determined to be 3 μM. Also, immunofluorescence, western blotting, and image quantification analyses were performed to test the rotenone exposure on the meiotic maturation, total and mitochondrial ROS, mitochondrial function and biogenesis, mitophagy and apoptosis in porcine oocytes. Further experiments showed that rotenone treatment induced mitochondrial dysfunction and failure of mitochondrial biogenesis by repressing the level of SIRT1 during in vitro maturation of porcine oocytes. In addition, rotenone treatment reduced the ratio of active mitochondria to total mitochondria, increased ROS production, and decreased ATP production. The levels of LC3 and active-caspase 3 were significantly increased by rotenone treatment, indicating that mitochondrial dysfunction induced by rotenone increased mitophagy but eventually led to apoptosis. Collectively, these results suggest that rotenone interferes with porcine oocyte maturation by inhibiting mitochondrial function., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Heo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2022
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37. Epigallocatechin-3-gallate protects porcine oocytes against post-ovulatory aging through inhibition of oxidative stress.
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Zhou D, Sun MH, Jiang WJ, Li XH, Lee SH, Heo G, Niu YJ, Ock SA, and Cui XS
- Subjects
- Animals, Aging, Glutathione, Oxidative Stress, Swine, Catechin pharmacology, Oocytes
- Abstract
Increased levels of oxidative stress are major factors that drive the process of post-ovulatory oocyte aging. Epigallocatechin-3-gallate (EGCG), which accounts for up to 50% of the catechins, possesses versatile biological functions, including preventing or treating diabetes, cancer, and heart diseases. The aim of this study was to explore whether EGCG can delay porcine oocyte aging by preventing oxidative stress. Metaphase II (MII) oocytes were cultured for 48 h with different concentrations of EGCG (0-100 μM) in vitro as a post-ovulatory aging model. An optimal concentration of 5 μM EGCG maintained oocyte morphology and developmental competence during aging. The oocytes were randomly divided into five groups: fresh, 24 h control, 24 h EGCG, 48 h control, and 48 h EGCG. The results suggest that EGCG significantly prevents aging-induced oxidative stress, glutathione (GSH) reduction, apoptosis, and autophagy. Moreover, mitochondria DNA copy number was decreased, and the number of active mitochondria and adenosine triphosphate (ATP) levels significantly increased by supplementation with EGCG. Thus, EGCG has a preventive role against aging in porcine post-ovulatory oocytes due to its ability to inhibit oxidative stress and promote mitochondrial biogenesis.
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- 2022
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38. Delivery of RNA Therapeutics: The Great Endosomal Escape!
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Dowdy SF, Setten RL, Cui XS, and Jadhav SG
- Subjects
- Humans, Endosomes metabolism, RNA, Small Interfering genetics, RNA, Small Interfering therapeutic use, RNA, Small Interfering chemistry, Oligonucleotides, Antisense genetics, Oligonucleotides, Antisense therapeutic use, Oligonucleotides, Antisense metabolism, Oligonucleotides metabolism, Lipid Bilayers metabolism, COVID-19 genetics, COVID-19 therapy
- Abstract
RNA therapeutics, including siRNAs, antisense oligonucleotides, and other oligonucleotides, have great potential to selectively treat a multitude of human diseases, from cancer to COVID to Parkinson's disease. RNA therapeutic activity is mechanistically driven by Watson-Crick base pairing to the target gene RNA without the requirement of prior knowledge of the protein structure, function, or cellular location. However, before widespread use of RNA therapeutics becomes a reality, we must overcome a billion years of evolutionary defenses designed to keep invading RNAs from entering cells. Unlike small-molecule therapeutics that are designed to passively diffuse across the cell membrane, macromolecular RNA therapeutics are too large, too charged, and/or too hydrophilic to passively diffuse across the cellular membrane and are instead taken up into cells by endocytosis. However, similar to the cell membrane, endosomes comprise a lipid bilayer that entraps 99% or more of RNA therapeutics, even in semipermissive tissues such as the liver, central nervous system, and muscle. Consequently, before RNA therapeutics can achieve their ultimate clinical potential to treat widespread human disease, the rate-limiting delivery problem of endosomal escape must be solved in a clinically acceptable manner.
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- 2022
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39. Increased Omega-3 Fatty Acid Intake Is Associated with Low Grip Strength in Elderly Korean Females.
- Author
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Bae YJ, Cui XS, and Shin SH
- Subjects
- Aged, Docosahexaenoic Acids metabolism, Eicosapentaenoic Acid metabolism, Female, Hand Strength, Humans, Male, Nutrition Surveys, Fatty Acids, Omega-3 metabolism, Sarcopenia prevention & control
- Abstract
Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have anti-inflammatory properties and have recently been considered essential factors for maintaining muscle health. This study aimed to investigate the relationship between omega-3 fatty acid intakes and sarcopenia by assessing grip strength in elderly Koreans who are at risk of sarcopenia. This study was conducted on 5529 individuals (2449 males and 3080 females) aged ≥65 years from the raw data of the Korea National Health and Nutrition Examination Survey 2015−2019. In this study, we analyzed the association between EPA and DHA intake, calculated from a 24-h recall method data, and grip strength, a diagnostic criterion for sarcopenia. The cut-off values for low grip strength were <26 kg for males and <18 kg for females, which were set for the Asian population. The results indicated that elderly females consuming EPA and DHA below the adequate intake (AI) had significantly lower grip strength (p < 0.0001) and, had a higher percentage contribution from carbohydrates, but a significantly lower percentage contribution from protein (p < 0.0001), compared to elderly females consuming EPA and DHA at or above the AI. In addition, after adjusting for confounding factors, the odds of low grip strength were 0.777 times lower among elderly females consuming EPA and DHA at or above the AI than those consuming EPA and DHA below the AI (95% confidence interval: 0.616−0.979, p = 0.0322). These results suggest that sufficient intake of EPA and DHA is pivotal to mitigate a reduction in grip strength and to improve the quality of nutrient intake among elderly females.
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- 2022
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40. Effects of high-fidelity simulation teaching on nursing students' knowledge, professional skills and clinical ability: A meta-analysis and systematic review.
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Lei YY, Zhu L, Sa YTR, and Cui XS
- Subjects
- Clinical Competence, Humans, Knowledge, Education, Nursing, High Fidelity Simulation Training, Students, Nursing
- Abstract
Objective: This meta-analysis was designed to systematically determine the effect of high-fidelity simulation teaching on nursing students' knowledge level, professional skill level and clinical ability., Background: High-fidelity simulation is an increasingly popular pedagogical approach in nursing education. It provides students with opportunity to practice in a variety of simulations before entering clinical practice through a variety of real-life situational experiences and many institutions and educators have embraced this method for enhancing access to clinical skills. However, evidence for the effectiveness of the method in nursing teaching remains scarce., Design: A meta-analysis and systematic review., Methods: The following Chinese and English databases were searched for relevant articles: PubMed, Embase, Cochrane library, Web of Science, CNKI (China National Knowledge Infrastructure) and Wangfang. The search encompassed the establishment of these databases up until November 2021. Two reviewers separately entered the data into Review Manager Software 5.3., Results: A total of 15 studies were included in this study. High-fidelity simulation significantly increased nursing students' knowledge acquisition (SMD = 1. 37, 94%CI:0. 73-2. 00,P <0. 0001), enhanced nursing students'professional skills (SMD = 0. 90, 95%CI:0. 36-1. 44,P = 0. 0001). In terms of clinical practice ability outcomes, high-fidelity simulation significantly improved the levels of critical thinking ability (SMD = 0. 58, 95%CI:0. 09-1. 07,P <0. 00001), Clinical judgement ability (SMD = 1. 34, 95%CI:0. 38-2. 31,P=0. 006) and communication skills (SMD = 2. 62, 95%CI:1. 84-3. 40,P <0. 001) of nursing students., Conclusions: We found that high-fidelity simulation have strong educational effects in nursing education, helping nursing students to increase knowledge acquisition, enhance professional skills and cultivate their clinical practice ability (critical thinking ability, communication skills and clinical judgement ability). These findings can provide guidance for nursing educators, indicating that the use of High-fidelity simulation teaching represents an effective solution for transitioning students from the learning environment to clinical practice., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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41. High Temperature Disrupts Organelle Distribution and Functions Affecting Meiotic Maturation in Porcine Oocytes.
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Lee SH, Sun MH, Zhou D, Jiang WJ, Li XH, Heo G, and Cui XS
- Abstract
Heat stress (HS) has been known to cause reproductive failure in animals, especially in summer. HS severely affects the developmental potential of oocytes and leads to low fertility rates. Previous studies have reported that HS compromises embryo development in bovine oocytes, and reduces ovarian development in mice, thereby impairing reproductive function in animals. However, the effect of high temperature (HT) on the organelles of porcine oocytes is unknown. In this study, we reported that exposure to HT for 24 h (41°C) significantly decreased meiotic maturation in porcine oocytes ( p < 0.05). Further experiments on organelles found that HT induced mitochondrial dysfunction, increased abnormal mitochondrial distribution, and decreased mitochondrial membrane potential (MMP). We also found that HT induced abnormal endoplasmic reticulum (ER) distribution and higher expression of glucose regulatory protein 78 (GRP78), suggesting that HT exposure induces ER stress. Our results also indicated that exposure to HT induced abnormal distribution and dysfunction of the Golgi apparatus, which resulted from a decrease in the expression of the vesicle transporter, Ras-related protein Rab-11A (RAB11A). In addition, we found that HT exposure led to lysosomal damage by increasing the expression of lysosome-associated membrane protein 2 ( LAMP2 ) and microtubule-associated protein 1A/1B-light chain 3 (LC3). In summary, our study revealed that HT exposure disrupts organelle dynamics, which further leads to the failure of meiotic maturation in porcine oocytes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lee, Sun, Zhou, Jiang, Li, Heo and Cui.)
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- 2022
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42. ROMO1 is required for mitochondrial metabolism during preimplantation embryo development in pigs.
- Author
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Zhou D, Sun MH, Lee SH, and Cui XS
- Abstract
Background: Reactive oxygen species (ROS) modulator 1 (ROMO1) is a mitochondrial membrane protein that is essential for the regulation of mitochondrial ROS production and redox sensing. ROMO1 regulates ROS generation within cells and is involved in cellular processes, such as cell proliferation, senescence, and death. Our purpose is to investigates the impact of ROMO1 on the mitochondria during porcine embryogenesis., Results: We found that high expression of ROMO1 was associated with porcine preimplantation embryo development, indicating that ROMO1 may contribute to the progression of embryogenesis. Knockdown of ROMO1 disrupted porcine embryo development and blastocyst quality, thereby inducing ROS production and decreasing mitochondrial membrane potential. Knockdown of ROMO1 induced mitochondrial dysfunction by disrupting the balance of OPA1 isoforms to release cytochrome c, reduce ATP, and induce apoptosis. Meanwhile, ROMO1 overexpression showed similar effects as ROMO1 KD on the embryos. Overexpression of ROMO1 rescued the ROMO1 KD-induced defects in embryo development, mitochondrial fragmentation, and apoptosis., Conclusions: ROMO1 plays a critical role in embryo development by regulating mitochondrial morphology, function, and apoptosis in pigs., (© 2021. The Author(s).)
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- 2021
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43. Derivation of iPSC lines from two idiopathic ASD patients (OFi001-A, OFi002-A).
- Author
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Guo H, Jin ZL, Yao X, Park J, Gwon YP, Kim S, Kim KP, Cui XS, Kim NH, Yoo H, and Han DW
- Subjects
- Cell Differentiation, Humans, Kruppel-Like Factor 4, Leukocytes, Mononuclear, Autism Spectrum Disorder, Induced Pluripotent Stem Cells
- Abstract
Here we described two human induced pluripotent stem cell (hiPSC) lines from peripheral blood mononuclear cells (PBMCs) of idiopathic autism spectrum disorder (ASD) patients through forced expression of OCT4, SOX2, KLF4, and c-MYC. The hiPSC lines displayed morphology, gene expression patterns, and pluripotential differentiation potentials similar to those of human embryonic stem cells (hESCs). The hiPSC lines from idiopathic ASD patients might be useful to unveil the underlying mechanism of idiopathic ASD and finding its therapeutics., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2021
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44. Acetyl-CoA synthases are essential for maintaining histone acetylation under metabolic stress during zygotic genome activation in pigs.
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Zhou W, Nie ZW, Zhou DJ, and Cui XS
- Subjects
- Acetate-CoA Ligase genetics, Acetylation, Adenosine Triphosphate metabolism, Animals, Embryo Culture Techniques, Parthenogenesis, Sirtuin 1 metabolism, Sirtuin 3 metabolism, Sus scrofa, Acetate-CoA Ligase metabolism, Acetates metabolism, Acetyl Coenzyme A metabolism, Energy Metabolism, Gene Expression Regulation, Developmental, Histones metabolism, Protein Processing, Post-Translational, Zygote enzymology
- Abstract
ACSS1/2 converts acetate into acetyl-coenzyme A, which contributes to histone acetylation in the mitochondria and cytoplasm. Zygotic genome activation (ZGA) is critical for embryo development involving drastic histone modification. An efficient crRNAs-Cas13a targeting strategy was employed to investigate the ACSS1/2 function during ZGA. The results showed that nuclear accumulation of ACSS1 and ACSS2 occurs during ZGA. Knockdown of ACSS1/2 did not affect blastocyst formation when using a normal medium. On culturing embryos in a medium with acetate and no pyruvate (-P + Ace), knockdown of ACSS1 did not affect histone acetylation levels but significantly reduced ATP levels, whereas knockdown of ACSS2 significantly reduced histone acetylation levels in porcine embryos. Inhibition of fatty acid beta-oxidation by etomoxir significantly reduced ATP levels, which could be restored by acetate. The histone acetylation levels in the ACSS1 and ACSS2 knockdown groups both decreased considerably after etomoxir treatment. Moreover, acetate showed dose-dependent effects on SIRT1 and SIRT3 levels when under metabolic stress. The C-terminus of ACSS1 regulated the nuclear translocation. In conclusion, ACSS1/2 helps to maintain ATP and histone acetylation levels in porcine early embryos under metabolic stress during ZGA., (© 2021 Wiley Periodicals LLC.)
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- 2021
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45. Editorial: Quality Control of Mammalian Oocyte Meiotic Maturation: Causes, Molecular Mechanisms and Solutions.
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Wang Y, Schatten H, Cui XS, and Sun SC
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Published
- 2021
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46. The complete mitochondrial genome of Dryopteris crassirhizoma Nakai (Dryopteridaceae, Dryopteris Adanson).
- Author
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Song YY, Cui XS, Xu L, Xing YP, Bian C, Qiao Y, Yang YY, and Kang TG
- Abstract
The complete mitochondrial genome of Dryopteris crassirhizoma was sequenced for the first time. The mitochondrial genome length was 313,346 bp, with 48.58% GC contents. There were 94 genes annotated, including 27 known protein-coding genes, 49 tRNAs , and 18 rRNAs . The maximum likelihood method was used to establish the phylogenetic tree of six species. The phylogenetic results showed that D. crassirhizoma was sister to Ophioglossum californicum. It reveals the genetic relationship between different species and provides a theoretical basis for the establishment of a classification system., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)
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- 2021
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47. Bezafibrate prevents aging in in vitro -matured porcine oocytes.
- Author
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Kim JY, Zhou D, and Cui XS
- Abstract
Bezafibrate, a fibrate drug used as a lipid-lowering agent to treat hyperlipidemia, is a pan-agonist of peroxisome proliferator-activated receptor alpha. It can enhance mitochondrial fatty acid oxidation, oxidative phosphorylation, and mitochondrial biogenesis. After ovulation, oocytes may get arrested at the metaphase II (MII) stage until fertilization beyond optimal timing, which is termed as post-ovulatory aging. Post-ovulatory aging is a disease that degrades DNA, mitochondria, and oxidative system, and has a negative impact on embryo development and quality; however, the impact of bezafibrate during post-ovulatory aging has not been fully defined. In the present study, we assessed the ability of bezafibrate to prevent the progression of aging in in vitro conditions as well as the underlying mechanisms in pigs. An appropriate concentration of this drug (50 μM) was added, and then oxidative stress, reactive oxygen species downstream, mitochondrial biogenesis, and mitochondrial function were analyzed via immunofluorescence staining and real-time polymerase chain reaction. Bezafibrate significantly alleviated reactive oxygen species and ameliorated glutathione production simultaneously in oocytes and embryos. Moreover, it diminished H2A.X and attenuated CASPASE 3 expression produced by oxidative stress in oocytes and embryos. Furthermore, bezafibrate remarkably improved the mitochondrial function and blastocyst quality as well as markedly reduced the mitochondria/TOM20 ratio and mtDNA copy number. The elevated PARKIN level indicated that mitophagy was induced by bezafibrate treatment after post-ovulatory aging. Collectively, these results suggest that bezafibrate beneficially affects against porcine post-ovulatory oocyte aging in porcine by its antioxidant property and mitochondrial protection., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2021 Korean Society of Animal Science and Technology.)
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- 2021
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48. Ral GTPase is essential for actin dynamics and Golgi apparatus distribution in mouse oocyte maturation.
- Author
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Sun MH, Hu LL, Zhao CY, Lu X, Ren YP, Wang JL, Cui XS, and Sun SC
- Abstract
Background: Ral family is a member of Ras-like GTPase superfamily, which includes RalA and RalB. RalA/B play important roles in many cell biological functions, including cytoskeleton dynamics, cell division, membrane transport, gene expression and signal transduction. However, whether RalA/B involve into the mammalian oocyte meiosis is still unclear. This study aimed to explore the roles of RalA/B during mouse oocyte maturation., Results: Our results showed that RalA/B expressed at all stages of oocyte maturation, and they were enriched at the spindle periphery area after meiosis resumption. The injection of RalA/B siRNAs into the oocytes significantly disturbed the polar body extrusion, indicating the essential roles of RalA/B for oocyte maturation. We observed that in the RalA/B knockdown oocytes the actin filament fluorescence intensity was significantly increased at the both cortex and cytoplasm, and the chromosomes were failed to locate near the cortex, indicating that RalA/B regulate actin dynamics for spindle migration in mouse oocytes. Moreover, we also found that the Golgi apparatus distribution at the spindle periphery was disturbed after RalA/B depletion., Conclusions: In summary, our results indicated that RalA/B affect actin dynamics for chromosome positioning and Golgi apparatus distribution in mouse oocytes.
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- 2021
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49. EB1 Is Essential for Spindle Formation and Chromosome Alignment During Oocyte Meiotic Maturation in Mice.
- Author
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Zhou D, Nie ZW, and Cui XS
- Subjects
- Animals, Chromosomes, Mice, Microtubules, Oocytes, Meiosis, Spindle Apparatus
- Abstract
The cytoskeleton plays an orchestrating role in polarized cell growth. Microtubules (MTs) not only play critical roles in chromosome alignment and segregation but also control cell shape, division, and motility. A member of the plus-end tracking proteins, end-binding protein 1 (EB1), regulates MT dynamics and plays vital roles in maintaining spindle symmetry and chromosome alignment during mitosis. However, the role of EB1 in mouse oocyte meiosis remains unknown. Here, we examined the localization patterns and expression levels of EB1 at different stages. EB1 protein level was found to be stable during meiosis. EB1 mainly localized along the spindle and had a similar localization pattern as that of α-tubulin. The EB1 protein was degraded with a Trim-Away method, and the results were further confirmed with western blotting and immunofluorescence. At 12 h of culture after EB1 knockdown (KD), a reduced number of mature MII oocytes were observed. EB1 KD led to spindle disorganization, chromosome misalignment, and missegregation; β-catenin protein binds to actin via the adherens junctional complex, which was significantly reduced in the EB1 KD oocytes. Collectively, we propose that the impairment of EB1 function manipulates spindle formation, thereby promoting chromosomal loss, which is expected to fuel aneuploidy and possibly fertilization failure.
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- 2021
- Full Text
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50. The effects of mindfulness-based interventions on nursing students: A meta-analysis.
- Author
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Chen X, Zhang B, Jin SX, Quan YX, Zhang XW, and Cui XS
- Subjects
- Anxiety prevention & control, China, Depression prevention & control, Humans, Mindfulness, Students, Nursing
- Abstract
Background: Recently, mindfulness interventions have been extensively applied in the field of nursing education. However, no consensus has been reached on whether these interventions can reduce anxiety and depression in nursing students., Objective: This meta-analysis was designed to determine the effect of mindfulness interventions on levels of depression, anxiety, stress and mindfulness for nursing students., Design: Meta-analysis of randomized controlled trials., Methods: The following Chinese and English databases were searched for relevant articles: Pubmed, Embase, Cochrane library, Web of Science, CNKI (China National Knowledge Infrastructure) and Wanfang. The search encompassed the establishment of these databases up until January 2020. Two reviewers separately entered the data into Review Manager Software 5.3., Results: A total of 10 randomized controlled trials (RCTs) were reviewed. It was found that mindfulness interventions significantly lowered levels of depression (SMD = -0.42, 95% CI:-0.56 to -0.28, P < 0.001), anxiety (SMD = -0.32, 95% CI:-0.47 to -0.17, P < 0.001) and stress (SMD = -0.50, 95% CI:-0.65 to -0.35, P < 0.001) in nursing students. Furthermore, the interventions raised levels of mindfulness in this group (SMD = 0.54, 95% CI:0.33-0.75, P < 0.001)., Conclusions: Mindfulness interventions can significantly reduce nursing students' negative emotions, helping them to manage their stress and anxiety. College nursing educators should consider adopting mindfulness interventions in nursing education to promote the mental health of students., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
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