Publications by authors named "Qingyong Meng"

84 Publications

Ectopic Expression of Induces Stenospermocarpy and Sugar Accumulation in Tomato Fruits.

Front Plant Sci 2021 17;12:759047. Epub 2021 Nov 17.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.

Seedless fruits are favorable in the market because of their ease of manipulation. Sucrose transporters (SUTs or SUCs) are essential for carbohydrate metabolism in plants. Whether SUTs participate directly in causing stenospermocarpy, thereby increasing fruit quality, remains unclear. Three , namely, , , and from , were characterized and ectopic expression in tomatoes. - and -overexpressing lines had similar flower and fruit phenotypes compared with those of the wild type. -overexpressing lines produced longer petals and pistils, an abnormal stigma, much less and shrunken pollen, and firmer seedless fruits. Moreover, produced fruits from all -overexpressing lines had a higher soluble solid content and sugar concentration. Transcriptomic analysis revealed more genes associated with carbohydrate metabolism and sugar transport and showed downregulation of auxin- and ethylene-related signaling pathways during early fruit development in -overexpressing lines relative to that of the wild type. Our findings demonstrated that stenospermocarpy can be induced by overexpression of through a consequential reduction in nutrient delivery to pollen at anthesis, with a subsequent downregulation of the genes involved in carbohydrate metabolism and hormone signaling. These commercially desirable results provide a new strategy for bioengineering stenospermocarpy in tomatoes and in other fruit plants.
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http://dx.doi.org/10.3389/fpls.2021.759047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637806PMC
November 2021

Circulating Natural Autoantibodies to HER2-Derived Peptides Performed Antitumor Effects on Oral Squamous Cell Carcinoma.

Front Pharmacol 2021 5;12:693989. Epub 2021 Nov 5.

Beijing Institute of Dental Research, Beijing Stomatological Hospital, Capital Medical University, Beijing, China.

Natural autoantibodies play a crucial role in destruction of malignant tumors due to immune surveillance function. Epidermal growth factor receptor 2 (HER2) has been found to be highly expressed in a variety of epithelial tumors including oral squamous cell carcinoma (OSCC). The present study was thus undertaken to investigate the effect of anti-HER2 natural autoantibodies on OSCC. Compared with cancer-adjacent tissues, cancer tissues from OSCC patients exhibited higher HER2 expression especially in those with middle & advanced stage OSCC. Plasma anti-HER2 IgG levels examined with an enzyme-linked immunosorbent assay (ELISA) developed in-house showed differences between control subjects, individuals with oral benign tumor and patients with OSCC. In addition, anti-HER2 IgG-abundant plasma was screened from healthy donors to treat OSCC cells and to prepare for anti-HER2 intravenous immunoglobulin (IVIg). Both anti-HER2 IgG-abundant plasma and anti-HER2 IVIg could significantly inhibit proliferation and invasion of OSCC cells by inducing the apoptosis, and also regulate apoptosis-associated factors and epithelial-mesenchymal transition (EMT), respectively. Besides, the complement-dependent cytotoxicity (CDC) pathway was likely to contribute to the anti-HER2 IgG mediated inhibition of OSCC cells. After the HER2 gene was knocked down with HER2-specific siRNAs, the inhibitory effects on OSCC cell proliferation and apoptotic induction faded away. In conclusion, human plasma IgG, or IVIg against HER2 may be a promising agent for anti-OSCC therapy.
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http://dx.doi.org/10.3389/fphar.2021.693989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602057PMC
November 2021

Hetero/Homo-Complexes of Sucrose Transporters May Be a Subtle Mode to Regulate Sucrose Transportation in Grape Berries.

Int J Mol Sci 2021 Nov 8;22(21). Epub 2021 Nov 8.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.

The sugar distribution mechanism in fruits has been the focus of research worldwide; however, it remains unclear. In order to elucidate the relevant mechanisms in grape berries, the expression, localization, function, and regulation of three sucrose transporters were studied in three representative varieties. Both and expression levels were positively correlated with sugar accumulation in grape berries, whereas showed a negative relationship. The alignment analysis and sucrose transport ability of isolated SUCs were determined to reflect coding region variations among , Ruper, and , indicating that functional variation existed in one SUT from different varieties. Furthermore, potentially oligomerized abilities of VvSUCs colocalized in the sieve elements of the phloem as plasma membrane proteins were verified. The effects of oligomerization on transport properties were characterized in yeast. VvSUC11 and VvSUC12 are high-affinity/low-capacity types of SUTs that stimulate each other by upregulating and , inhibiting sucrose transport, and downregulating the of VvSUC27. Thus, changes in the distribution of different SUTs in the same cell govern functional regulation. The activation and inhibition of sucrose transport could be achieved in different stages and tissues of grape development to achieve an effective distribution of sugar.
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http://dx.doi.org/10.3390/ijms222112062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584533PMC
November 2021

Lactoferrin, a Critical Player in Neonate Intestinal Development: RHLF may be a Good Choice in Formula.

J Agric Food Chem 2021 Aug 29;69(31):8726-8736. Epub 2021 Jul 29.

Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.

Lactoferrin (LF) is a bioactive glycoprotein in human milk and has positive effects on neonates. The LF knockout mouse model was generated as a mother mouse that provided LF-free milk. The intestinal development of suckling neonates drinking normal milk and LF-free milk was studied. The results showed that the intestinal density, maturity, and barrier integrity of mice drinking LF-free milk were lower than those of mice drinking normal milk. Therefore, the importance of adding lactoferrin to the human formula is considered. Human lactoferrin (HLF), bovine lactoferrin (BLF), and recombinant HLF (RHLF) were used to compare their functional impact on Caco-2 cell lines. Cell proliferation, differentiation, the establishment of the intestinal barrier, and protective effects on lipopolysaccharide injury were detected. Our results showed that RHLF exhibited more similar functions to HLF than BLF and showed the combined advantages of HLF and BLF in promoting the establishment of the intestinal barrier. This study emphasizes the important role of LF in neonatal intestinal development and provides a theoretical basis for the availability of RHLF.
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http://dx.doi.org/10.1021/acs.jafc.1c03129DOI Listing
August 2021

Melatonin promotes in vitro maturation of vitrified-warmed mouse GV oocytes potentially by modulating MAD2 protein expression of SAC component through MTRs.

Cryobiology 2021 10 21;102:82-91. Epub 2021 Jul 21.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address:

Previous studies have shown that melatonin (MT) can ameliorate vitrification-inflicted damage in mouse germinal vesicle (GV) oocytes, however, the key mechanistic basis of this improvement still remains poorly understood. This study was conducted to investigate whether MT can improve in vitro developmental potential of vitrified-warmed GV oocytes through its receptors. The fresh oocytes were randomly divided into four groups: untreated (control group, F), vitrified by open-pulled straw method (vitrification group, V), vitrification group with 100 nmol/L MT supplementation (vitrification + MT group, VM), and with 100 nmol/L MT plus 100 nmol/L luzindole administration (vitrification + MT + luzindole group, VML) or with 50 nmol/L ramelteon addition (vitrification + ramelteon group; VR). After warming, oocytes were cultured in vitro, and MT receptors (MTRs), MAD2 (mitotic arrest deficient 2), Securin and CyclinB1 protein levels and spindle morphology were evaluated. The ratio of oocytes developed to the metaphase I (MI) and metaphase II (MII) stages was also assessed. The results showed that after vitrification-warming, the in vitro maturation rate of GV oocytes was significantly lower compared to the control (F) group. Vitrification also significantly impaired the spindle morphology, decreased the protein level of MTRs and Securin, and decreased MAD2 levels in MI oocytes. However, when MT or ramelteon (MTRs agonist) were added (group wise) to warming and maturation media, the maturation rate of GV oocytes was significantly increased, the normal proportion of the spindle morphology increased, and the expression level of MAD2 increased in their resulting MI oocytes compared to the vitrification group. However, following addition of both MT and ramelteon, the maturation rate of GV oocyte showed no significant difference between VML and vitrification groups. The spindle morphology and MAD2 levels in MI oocytes were comparable to the vitrification group but differed significantly from the VM group. Taken together, finding of the present study shows that MT (100 nmol/L) can ameliorate the in vitro maturation of vitrified-warmed mouse GV oocytes, potentially by improving the spindle morphology, modulating MAD2 protein level and promoting the development of MI stage oocytes through MTRs.
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http://dx.doi.org/10.1016/j.cryobiol.2021.07.008DOI Listing
October 2021

Melatonin improves the first cleavage of parthenogenetic embryos from vitrified-warmed mouse oocytes potentially by promoting cell cycle progression.

J Anim Sci Biotechnol 2021 Jul 16;12(1):84. Epub 2021 Jul 16.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China.

Background: This study investigated the effect of melatonin (MT) on cell cycle (G1/S/G2/M) of parthenogenetic zygotes developed from vitrified-warmed mouse metaphase II (MII) oocytes and elucidated the potential mechanism of MT action in the first cleavage of embryos.

Results: After vitrification and warming, oocytes were parthenogenetically activated (PA) and in vitro cultured (IVC). Then the spindle morphology and chromosome segregation in oocytes, the maternal mRNA levels of genes including Miss, Doc1r, Setd2 and Ythdf2 in activated oocytes, pronuclear formation, the S phase duration in zygotes, mitochondrial function at G1 phase, reactive oxygen species (ROS) level at S phase, DNA damage at G2 phase, early apoptosis in 2-cell embryos, cleavage and blastocyst formation rates were evaluated. The results indicated that the vitrification/warming procedures led to following perturbations 1) spindle abnormalities and chromosome misalignment, alteration of maternal mRNAs and delay in pronucleus formation, 2) decreased mitochondrial membrane potential (MMP) and lower adenosine triphosphate (ATP) levels, increased ROS production and DNA damage, G1/S and S/G2 phase transition delay, and delayed first cleavage, and 3) increased early apoptosis and lower levels of cleavage and blastocyst formation. Our results further revealed that such negative impacts of oocyte cryopreservation could be alleviated by supplementation of warming, recovery, PA and IVC media with 10 mol/L MT before the embryos moved into the 2-cell stage of development.

Conclusions: MT might promote cell cycle progression via regulation of MMP, ATP, ROS and maternal mRNA levels, potentially increasing the first cleavage of parthenogenetic zygotes developed from vitrified-warmed mouse oocytes and their subsequent development.
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http://dx.doi.org/10.1186/s40104-021-00605-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283938PMC
July 2021

MiR-29ab1 Cluster Resists Muscle Atrophy Through Inhibiting MuRF1.

DNA Cell Biol 2021 Sep 13;40(9):1167-1176. Epub 2021 Jul 13.

The State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.

Skeletal muscle has great plasticity. An increase in protein degradation can cause muscle atrophy. Atrogin-1 and muscle ring finger-1 (MuRF1) are dramatically upregulated in various muscle atrophy. Inhibition of Atrogin-1 and MuRF1 protects against muscle atrophy. MiR-29 plays an important regulatory role in skeletal muscle development. However, the function of miR-29 in skeletal muscle protein metabolism is not clear. To investigate the function of miR-29, we generated miR-29 knockout mice and the miR-29ab1 cluster overexpression mice. The disruption of miR-29 led to severe atrophy of skeletal muscle during puberty, and the muscle-specific overexpression of the miR-29ab1 cluster protected against denervation-induced and fasting-induced muscle atrophy. Furthermore, the overexpression of miR-29a, b mimics in myotubes resisted the muscle atrophy. MuRF1 was the direct target gene of miR-29a, b. These results demonstrate that miR-29ab1 cluster plays a critical role in the maintenance of skeletal muscle. MiR-29ab1 cluster is the excellent inhibitor of MuRF1, ultimately indicating that miR-29ab1 cluster is good therapeutic molecule candidate for adulthood.
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http://dx.doi.org/10.1089/dna.2021.0267DOI Listing
September 2021

MiR-25-3p regulates the differentiation of intramuscular preadipocytes in goat via targeting .

Arch Anim Breed 2021 18;64(1):17-25. Epub 2021 Jan 18.

Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China.

Adipocyte differentiation, which plays an important role in fat deposition, involves a complex molecular mechanism. MicroRNAs (miRNAs) are essential in this progress. Here, we showed that miR-25-3p expression had increased during goat intramuscular preadipocyte differentiation, which peaked at day 3. Using liposome transfection and qRT-PCR techniques, we found that knocking down miR-25-3p reduced the accumulation of lipid droplets by downregulating or upregulating the expression of , , , , and but upregulating the expression of . Overexpression of miR-25-3p results in the opposite. Furthermore, the dual luciferase assay showed that overexpression of miR-25-3p significantly inhibited luciferase activity of . These results showed that miR-25-3p has a binding site within the 3 -UTR of mRNA. Together, these findings indicate that miR-25-3p is a positive regulator of intramuscular preadipocyte differentiation via targeting to in goats.
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http://dx.doi.org/10.5194/aab-64-17-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128059PMC
January 2021

Inhibitory effects of circulating natural autoantibodies to CD47-derived peptides on OSCC cells.

Oral Dis 2021 May 24. Epub 2021 May 24.

Beijing Institute of Dental Research, Beijing Stomatological Hospital, Capital Medical University, Beijing, China.

Objectives: Natural autoantibodies serve as an important anti-tumorigenic component in the body. This study was thus designed to investigate whether circulating natural IgG autoantibodies against a cluster of differentiation 47 (CD47) could exert inhibitory effects on oral squamous cell carcinoma (OSCC).

Subjects And Methods: The expression levels of 13 tumor-targeted genes in three OSCC cell lines were analyzed by qPCR, and CD47 expression in OSCC tissues was also verified with IHC staining. An in-house ELISA was performed to analyze circulating anti-CD47 IgG levels in control subjects, oral benign tumor, and OSCC patients, and to detect anti-CD47 IgG-abundant plasma. Three OSCC cell lines were treated with anti-CD47 IgG-abundant and -deficient plasma, respectively, followed by the analysis of cell proliferation, apoptosis, and invasion/metastasis.

Results: The CD47 gene showed the highest expression among 13 genes detected in three OSCC cell lines; its expression was significantly higher in OSCC tissues than adjacent tissues. Plasma anti-CD47 IgG levels showed the differences between control subjects, oral benign tumor, and OSCC patients. Anti-CD47 IgG-abundant plasma could evidently reduce cell viability via suppressing p-AKT expression and inducing cell apoptosis and inhibit the invasion of all three OSCC cell lines.

Conclusions: Natural autoantibodies against CD47 may be a potential agent for OSCC immunotherapy.
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http://dx.doi.org/10.1111/odi.13922DOI Listing
May 2021

MiR-421 regulates goat intramuscular preadipocytes differentiation via targeting .

Anim Biotechnol 2021 Apr 29:1-11. Epub 2021 Apr 29.

Key Laboratory of Ministry of Education, Ministry of Education, Southwest Minzu University, Chengdu, China.

As a member of the MicroRNA s (miRNAs) family, miR-421 has been widely studied in regulating the proliferation and apoptosis of cancer cells a. However, there are still no reports on miR-421 in regulating adipocyte differentiation and its related mechanisms. Accordingly, this study aimed to investigate the potential involvement of miR-421 in goat intramuscular preadipocytes (P_IMA). The expression level of miR-421 was measured via quantitative real-time PCR during goat P_IMA differentiation. And the effects of miR-421 on goat P_IMA differentiation were studied by liposome transfection, Oil red O staining and qRT-PCR. Furthermore, the miR-421 target was searched and the underlying mechanism was clarified by luciferase reporter assay and rescue experiment. Our results showed that inhibition of miR-421 could accumulation of lipid droplets by upregulation the expression level of 2, , and . Further studies showed that fibroblast growth factor () was the direct target of miR-421. Knocking down of expression could inhibit lipid droplet formation and down-regulated the expression of key adipogenic regulatory genes. In addition, the rescue experiment revealed that is involved in miR-421-induced differentiation of goat P_IMA as a key factor. Overall, these findings indicate that miR-421 is a negative regulator in the progression of differentiation of goat P_IMA by inhibiting the expression of .
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http://dx.doi.org/10.1080/10495398.2021.1898414DOI Listing
April 2021

High-Dimensional Quantum Dynamics Study on Excitation-Specific Surface Scattering Including Lattice Effects of a Five-Atom Surface Cell.

J Chem Theory Comput 2021 May 27;17(5):2702-2713. Epub 2021 Apr 27.

Theoretische Chemie, Physikalisch-Chemisches Institut, Ruprecht-Karls Universität Heidelberg, Im Neuenheimer Feld 229, D-69120 Heidelberg, Germany.

In this work, high-dimensional (21D) quantum dynamics calculations on the mode-specific surface scattering of a carbon monoxide molecule on a copper(100) surface with lattice effects of a five-atom surface cell are performed through the multilayer multiconfiguration time-dependent Hartree (ML-MCTDH) method. We employ a surface model in which five surface atoms near the impact site are treated as fully flexible quantum particles, while all other more distant atoms are kept at fixed locations. To efficiently perform the 21D ML-MCTDH wave packet propagation, the potential energy surface is transferred to a canonical polyadic decomposition form with the aid of a Monte Carlo-based method. Excitation-specific sticking probabilities of CO on Cu(100) are computed, and lattice effects caused by the flexible surface atoms are demonstrated by comparison with sticking probabilities computed for a rigid surface. The dependence of the sticking probability of the initial state of the system is studied, and it is found that the sticking probability is reduced when the surface atom on the impact site is initially vibrationally excited.
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http://dx.doi.org/10.1021/acs.jctc.1c00241DOI Listing
May 2021

MiR-22 modulates brown adipocyte thermogenesis by synergistically activating the glycolytic and mTORC1 signaling pathways.

Theranostics 2021 25;11(8):3607-3623. Epub 2021 Jan 25.

State Key Laboratories for Agrobiotechnology and Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Biological Sciences, China Agricultural University, Beijing, China, 100193.

Brown adipose tissue (BAT) dissipates chemical energy as heat and has the potential to be a protective strategy to prevent obesity. microRNAs (miRNAs) are emerging as important posttranscriptional factors affecting the thermogenic function of BAT. However, the regulatory mechanism underlying miRNA-mediated energy metabolism in BAT is not fully understood. Here, we explored the roles of miR-22 in BAT thermogenesis and energy metabolism. Using global and conditional knockout mice as models and primary brown adipocytes as an system, we investigated the function of miR-22 in BAT thermogenesis and . miR-22 expression was upregulated in BAT in response to cold exposure and during brown preadipocyte differentiation. Both global and conditional knockout mice displayed BAT whitening, impaired cold tolerance, and decreased BAT thermogenesis. Moreover, we found that miR-22 deficiency impaired BAT glycolytic capacity, which is critical for thermogenesis. The mechanistic results revealed that miR-22 activated the mTORC1 signaling pathway by directly suppressing Tsc1 and concomitantly directly suppressing Hif1an, an inhibitor of Hif1α, which promotes glycolysis and maintains thermogenesis. Our findings identify miR-22 as a critical regulator in the control of thermogenesis in BAT and as a potential therapeutic target for human metabolic disorders.
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http://dx.doi.org/10.7150/thno.50900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914365PMC
July 2021

Author Correction: MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists.

Nat Commun 2020 Oct 15;11(1):5308. Epub 2020 Oct 15.

State Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41467-020-19103-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567098PMC
October 2020

Study of Circulating Natural Antibodies Against CD25 and FOXP3 in Type-2 Diabetes.

Clin Lab 2020 Aug;66(8)

Background: Natural antibodies are critical components for maintaining homeostasis of the immune system. Regulatory T (Treg) cells have indispensable effects on immunosuppressive function and peripheral immune tolerance. Both CD25 and FOXP3 are specifically expressed in Treg cells and their natural antibodies may protect against the development of type-2 diabetes (T2D). The present study aimed to test whether circulating antibodies against CD25 and FOXP3 were altered in first-episode patients with T2D.

Methods: An enzyme-linked immunosorbent assay (ELISA) was developed in-house to detect the levels of plasma IgG antibodies against five linear peptide antigens with three derived from CD25 (named CD25a, CD25b, CD25c) and two derived from FOXP3 (called FOXP3a and FOXP3b) among 200 first-episode patients with T2D and 220 healthy controls.

Results: Mann-Whitney U test showed a significant decrease in anti-CD25a IgG levels in patients with T2D as compared with the healthy controls (Z = -3.438, p = 0.0006), male patients mainly contributing to the decreased levels of anti-CD25a IgG levels (Z = -3.065, p = 0.002). The other four IgG tests demonstrated a lower level of plas-ma IgG antibodies in the patient group than the control group, but failed to show statistical significance (p > 0.01). ROC curve analysis indicated that the anti-CD25a IgG assay had the best sensitivity of 19.5% against the specificity of 90%.

Conclusions: Decreased anti-CD25 IgG levels in the circulation may represent a reduction in the number of Treg cells and detection of such antibodies may be beneficial to the understanding of immunological changes in T2D patients.
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http://dx.doi.org/10.7754/Clin.Lab.2020.191153DOI Listing
August 2020

Expression of Sucrose Transporters from Confer High Yield and Enhances Drought Resistance in Arabidopsis.

Int J Mol Sci 2020 Apr 9;21(7). Epub 2020 Apr 9.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.

Sucrose is the predominant form of sugar transported from photosynthetic (source) to non-photosynthetic (sink) organs in higher plants relying on the transporting function of sucrose transporters (SUTs or SUCs). Many SUTs have been identified and characterized in both monocots and dicots. However, the function of sucrose transporters (SUTs or SUCs) from is not clear. As the world's most planted grape species, owns three sucrose transport activity verified SUTs. In this study, we constructed three kinds of -overexpressing transgenic Arabidopsis. -overexpressing transgenic Arabidopsis was cultured on sucrose-supplemented medium. - and -overexpressing lines had similar thrived growth phenotypes, whereas the size and number of leaves and roots from -overexpressing lines were reduced compared with that of WT. When plants were cultured in soil, all SUT transgenic seedlings produced more number of leaves and siliques, resulting in higher yield (38.6% for -transformants) than that of WT. Besides, -transformants and -transformants enhanced drought resistance in Arabidopsis, providing a promising target for crop improvement.
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http://dx.doi.org/10.3390/ijms21072624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177370PMC
April 2020

Revisiting the Gaussian process regression for fitting high-dimensional potential energy surface and its application to the OH + HO→ O + HO reaction.

J Chem Phys 2020 Apr;152(13):134309

School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, West Youyi Road 127, 710072 Xi'an, China.

In this work, Gaussian process regression (GPR) for fitting a high-dimensional potential energy surface (PES) is revisited and implemented to construct the PES of OH + HO → O + HO. Using mixed kernel function and optimized distribution of the training database, only ∼3 × 10 energy points are needed to approach convergence, which implies the power of GPR in saving lots of computational cost. Moreover, the convergence of the GPR PES is inspected, leading to discussions on the advantages of the GPR fitting approach. By the segmented strategy [Meng et al., J. Chem. Phys. 144, 154312 (2016)], a GPR PES with a fitting error of ∼21 meV is constructed using ∼4600 energy points at the CCSD(T)-F12a/aug-cc-pVTZ level. The rate coefficients are then computed through the ring-polymer molecular dynamics (RPMD) method. An agreement between the present RPMD calculations and the previous observations is found, implying the accuracy of the present calculations. Moreover, the unusual feature of the Arrhenius curve is interpreted by a coupled harmonic oscillator model [Q. Meng, J. Phys. Chem. A 122, 8320 (2018)] together with a simple kinetics model.
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http://dx.doi.org/10.1063/1.5143544DOI Listing
April 2020

Secreted stromal protein ISLR promotes intestinal regeneration by suppressing epithelial Hippo signaling.

EMBO J 2020 04 4;39(7):e103255. Epub 2020 Mar 4.

State Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, China.

The Hippo-YAP signaling pathway plays an essential role in epithelial cells during intestinal regeneration and tumorigenesis. However, the molecular mechanism linking stromal signals to YAP-mediated intestinal regeneration and tumorigenesis is poorly defined. Here, we report a stroma-epithelium ISLR-YAP signaling axis essential for stromal cells to modulate epithelial cell growth during intestinal regeneration and tumorigenesis. Specifically, upon inflammation and in cancer, an oncogenic transcription factor ETS1 in stromal cells induces expression of a secreted protein ISLR that can inhibit Hippo signaling and activate YAP in epithelial cells. Deletion of Islr in stromal cells in mice markedly impaired intestinal regeneration and suppressed tumorigenesis in the colon. Moreover, the expression of stromal cell-specific ISLR and ETS1 significantly increased in inflamed mucosa of human IBD patients and in human colorectal adenocarcinoma, accounting for the epithelial YAP hyperactivation. Collectively, our findings provide new insights into the signaling crosstalk between stroma and epithelium during tissue regeneration and tumorigenesis.
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http://dx.doi.org/10.15252/embj.2019103255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110107PMC
April 2020

Analysis of plasma autoantibodies for inflammatory cytokines in patients with first-episode schizophrenia among a Chinese population.

J Neuroimmunol 2020 04 21;341:577165. Epub 2020 Jan 21.

Laboratory for Nursing Science & Institute of Laboratory Medicine, Guangdong Medical University, Dongguan 523808, China. Electronic address:

Neuroinflammation has been considered to be involved in the development of schizophrenia. This study aimed to study circulating autoantibodies for inflammatory cytokines in first-episode schizophrenia. A total of 181 patients and 197 controls were recruited for detection of plasma IgG antibodies against peptide antigens derived from interleukin 1α (IL1α), IL1ß, IL6, IL8 and tumour necrosis factor alpha (TNFα). The major finding was that patients with schizophrenia had significantly higher levels of anti-IL1ß IgG, anti-IL6 IgG and anti-IL8 IgG, and a significantly lower level of anti-IL1α IgG. This study suggests that inflammatory response may contribute to the development of schizophrenia.
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http://dx.doi.org/10.1016/j.jneuroim.2020.577165DOI Listing
April 2020

Dietary Selenium Supplementation Ameliorates Female Reproductive Efficiency in Aging Mice.

Antioxidants (Basel) 2019 Dec 11;8(12). Epub 2019 Dec 11.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.

Female reproductive (ovarian) aging is distinctively characterized by a markedly reduced reproductive function due to a remarkable decline in quality and quantity of follicles and oocytes. Selenium (Se) has been implicated in playing many important biological roles in male fertility and reproduction; however, its potential roles in female reproduction, particularly in aging subjects, remain poorly elucidated. Therefore, in the current study we used a murine model of female reproductive aging and elucidated how different Se-levels might affect the reproductive efficiency in aging females. Our results showed that at the end of an 8-week dietary trial, whole-blood Se concentration and blood total antioxidant capacity (TAOC) were significantly reduced in Se-deficient (0.08 mg Se/kg; Se-D) mice, whereas both of these biomarkers were significantly higher in inorganic (0.33 mg/kg; ISe-S) and organic (0.33 mg/kg; OSe-S) Se-supplemented groups. Similarly, compared to the Se-D group, Se supplementation significantly ameliorated the maintenance of follicles and reduced the rate of apoptosis in ovaries. Meanwhile, the rate of in vitro-produced embryos resulting from germinal vesicle (GV) oocytes was also significantly improved in Se-supplemented (ISe-S and OSe-S) groups compared to the Se-D mice, in which none of the embryos developed to the hatched blastocyst stage. RT-qPCR results revealed that mRNA expression of , , , , and genes in ovaries of aging mice was differentially modulated by dietary Se levels. A considerably higher mRNA expression of , , , and was observed in Se-supplemented groups compared to the Se-D group. Similarly, mRNA expression of and was significantly lower in Se-supplemented groups. Immunohistochemical assay also revealed a significantly higher expression of GPX4 in Se-supplemented mice. Our results reasonably indicate that Se deficiency (or marginal levels) can negatively impact the fertility and reproduction in females, particularly those of an advancing age, and that the Se supplementation (inorganic and organic) can substantiate ovarian function and overall reproductive efficiency in aging females.
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http://dx.doi.org/10.3390/antiox8120634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969897PMC
December 2019

miR-29a/b1 Inhibits Hair Follicle Stem Cell Lineage Progression by Spatiotemporally Suppressing WNT and BMP Signaling.

Cell Rep 2019 11;29(8):2489-2504.e4

State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing 100193, China; Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing 100193, China. Electronic address:

Hair follicle stem cells (HFSCs) and subsequent generations of matrix progeny make lineage choices by responding to spatiotemporal signals; however, the cues driving that specification are not well understood. Here, we demonstrate that the dynamics of microRNA (miR)-29 expression are inversely proportional to HFSC lineage progression. Furthermore, we show that sustained miR-29a/b1 overexpression in anagen or telogen in mice causes a short-hair phenotype and eventual hair loss by inhibiting the proliferation of HFSCs and matrix cells and likely preventing their differentiation. Conversely, in a loss-of-function in vivo model, miR-29a/b1 deficiency accelerates HFSC lineage progression in telogen. Mechanistically, miR-29a/b1 blocks HFSC lineage specification by spatiotemporally targeting Ctnnb1, Lrp6, Bmpr1a, and Ccna2. We further show that skin-specific Lrp6 or Bmpr1a ablation partially accounts for the short-hair phenotype. Overall, these synergistic targets reveal miR-29a/b1 as a high-fidelity antagonist of HFSC lineage progression and a potential therapeutic target for hair loss.
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http://dx.doi.org/10.1016/j.celrep.2019.10.062DOI Listing
November 2019

Neural-network potential energy surface with small database and high precision: A benchmark of the H + H system.

J Chem Phys 2019 Sep;151(11):114302

Department of Applied Chemistry, Northwestern Polytechnical University, West Youyi Road 127, 710072 Xi'an, China.

To deeply understand the neural-network (NN) fitting procedure in constructing a potential energy surface (PES) in a wide energy range with a rather small database, based on the existing BKMP2 PES of H + H, the relationship between NN function features and the size of the database is studied using the multiconfiguration time-dependent Hartree method for quantum dynamics calculations. First, employing 3843, 3843, 2024, and 1448 energy points, four independent NN-PESs are constructed to discuss the relationship among the size of the database, NN functional structure, and fitting accuracy. Dynamics calculations on these different NN PESs give similar reactive probabilities, which indicate that one has to balance the number of energy points for NN training and the number of neurons in the NN function. To explain this problem and try to resolve it, a quantitative model between the data volume and network scale is proposed. Then, this model is discussed and verified through 14 NN PESs fitted using 3843 energy points and various NN functional forms.
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http://dx.doi.org/10.1063/1.5118692DOI Listing
September 2019

Melatonin Improves In Vitro Development of Vitrified-Warmed Mouse Germinal Vesicle Oocytes Potentially via Modulation of Spindle Assembly Checkpoint-Related Genes.

Cells 2019 08 30;8(9). Epub 2019 Aug 30.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.

The present study aimed to investigate the effect of melatonin (MT) supplementation on in vitro maturation of vitrified mouse germinal vesicle (GV) oocytes. The fresh oocytes were randomly divided into three groups: untreated (control), or vitrified by open-pulled straw method without (vitrification group) or with MT supplementation (vitrification + MT group). After warming, oocytes were cultured in vitro, then the reactive oxygen species (ROS) and glutathione (GSH) levels, mitochondrial membrane potential, ATP levels, spindle morphology, mRNA expression of spindle assembly checkpoint (SAC)-related genes ), and their subsequent developmental potential in vitro were evaluated. The results showed that vitrification/warming procedures significantly decreased the percentage of GV oocytes developed to metaphase II (MII) stage, the mitochondrial membrane potential, ATP content, and GSH levels, remarkably increased the ROS levels, and significantly impaired the spindle morphology. The expressions of SAC-related genes were also altered in vitrified oocytes. However, when 10 mol/L MT was administered during the whole length of the experiment, the percentage of GV oocytes matured to MII stage was significantly increased, and the other indicators were also significantly improved and almost recovered to the normal levels relative to the control. Thus, we speculate that MT might regulate the mitochondrial membrane potential, ATP content, ROS, GSH, and expression of SAC-related genes, potentially increasing the in vitro maturation of vitrified-warmed mouse GV oocytes.
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http://dx.doi.org/10.3390/cells8091009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770451PMC
August 2019

A study of natural IgG antibodies against ATP-binding cassette subfamily C member 3 in oral squamous cell carcinoma.

J Cancer Res Ther 2019 ;15(4):921-926

Beijing Institution of Dental Research, Beijing Stomatological Hospital, Capital Medical University, Beijing, China.

Aims: ATP-binding cassette subfamily C member 3 (ABCC3) is involved in multidrug resistance and is overexpressed in some solid tumors. Recent work revealed an increase in circulating anti-ABCC3 antibodies in lung and esophageal cancers. This in vitro study was undertaken to investigate the effects of the natural IgG antibody against the ABCC3-derived peptide antigen on proliferation of oral squamous cell carcinoma (OSCC) cells and augment the development of efficient and effective treatments in patients with OSCC.

Subjects And Methods: An in-house enzyme-linked immunosorbent assay was applied to detect anti-ABCC3 IgG antibody in human plasma. Two OSCC cell lines, CAL27 and SCC15, were cultured with 20% plasma either positive or negative for anti-ABCC3 IgG. Cell proliferation was quantified by the CCK-8 method, and cell apoptosis and cell cycle distribution were analyzed by flow cytometry. The expression of the ABCC3 gene in the cell lines was analyzed by reverse transcriptase quantitative real-time polymerase chain reaction.

Results: The results showed that plasma anti-ABCC3 IgG significantly inhibited the proliferation of CAL27 cells but not SCC15 cells, although ABCC3 was expressed in both cell lines. The proportion of apoptotic cells was significantly higher in CAL27 cells treated with anti-ABCC3 IgG-positive plasma than in those treated with IgG-negative plasma. Cell cycle progression was arrested in CAL27 cells treated with anti-ABCC3 IgG-positive plasma.

Conclusions: Our data suggest that human plasma anti-ABCC3 IgG may be a promising agent in anti-OSCC therapy, although further studies are needed to arrive at a definitive conclusion.
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http://dx.doi.org/10.4103/jcrt.JCRT_150_18DOI Listing
February 2020

Role of Selenium and Selenoproteins in Male Reproductive Function: A Review of Past and Present Evidences.

Antioxidants (Basel) 2019 Aug 2;8(8). Epub 2019 Aug 2.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.

Selenium (Se) is an important trace mineral having many essential roles at the cellular and organismal levels in animal and human health. The biological effects of Se are mainly carried out by selenoproteins (encoded by 25 genes in humans and 24 in mice). As an essential component of selenoproteins, Se performs structural and enzymic roles; in the latter context it is well known for its catalytic and antioxidative functions. Studies involving different animal models have added great value to our understanding regarding the potential implications of Se and selenoproteins in mammalian fertility and reproduction. In this review, we highlight the implications of selenoproteins in male fertility and reproduction followed by the characteristic biological functions of Se and selenoproteins associated with overall male reproductive function. It is evident from observations of past studies (both animal and human) that Se is essentially required for spermatogenesis and male fertility, presumably because of its vital role in modulation of antioxidant defense mechanisms and other essential biological pathways and redox sensitive transcription factors. However, bearing in mind the evidences from mainstream literature, it is also advisable to perform more studies focusing on the elucidation of additional roles played by the peculiar and canonical selenoproteins i.e., glutathione peroxidase 4 (GPX4) and selenoprotein P (SELENOP) in the male reproductive functions. Nevertheless, search for the elucidation of additional putative mechanisms potentially modulated by other biologically relevant selenoproteins should also be included in the scope of future studies. However, as for the implication of Se in fertility and reproduction in men, though a few clinical trials explore the effects of Se supplementation on male fertility, due to inconsistencies in the recruitment of subjects and heterogeneity of designs, the comparison of such studies is still complicated and less clear. Therefore, further research focused on the roles of Se and selenoproteins is awaited for validating the evidences at hand and outlining any therapeutic schemes intended for improving male fertility. As such, new dimensions could be added to the subject of male fertility and Se supplementation.
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http://dx.doi.org/10.3390/antiox8080268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719970PMC
August 2019

Anti-TSNARE1 IgG plasma levels differ by sex in patients with schizophrenia in a Chinese population.

FEBS Open Bio 2019 10 4;9(10):1705-1712. Epub 2019 Sep 4.

Institute of Health Research & Innovation, University of the Highlands & Islands, Inverness, UK.

It was recently reported that levels of plasma IgG antibodies against peptide antigens derived from proteins encoded by schizophrenia-associated genes are altered in individuals with schizophrenia treated with antipsychotics. This study aimed to replicate the initial finding in antipsychotic-naïve patients with first-episode schizophrenia and to explore the possible mechanism by which immune tolerance of B cells may be altered in this disease. A total of 408 case-control plasma samples were collected for analysis of circulating IgG antibodies against fragments derived from TCF4, TSNARE1, ZNF804A, TRANK1, ERCC4, DPYD and CD25 using an in-house ELISA. The Mann-Whitney U-test revealed that patients with schizophrenia had a significant change in plasma anti-TSNARE1 and anti-CD25 IgG levels; male patients mainly contributed to the increased levels of anti-TSNARE1 IgG and anti-CD25 IgG. Receiver operating characteristic (ROC) curve analysis revealed that the anti-TSNARE1 IgG assay had an area under the ROC curve of 0.625 with a sensitivity of 15.7% and a specificity of 95.2%. Work on a B-cell model revealed that TRANK1-derived antigen treatments could enhance the proportions of CD83+ cells and apoptotic B cells when compared with TSNARE1-derived antigen and vehicle treatment. We conclude that there is a gender difference in autoimmune responses in schizophrenia and suggest that anti-TSNARE1 IgG may be indicative of schizophrenia in a subgroup of male patients.
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http://dx.doi.org/10.1002/2211-5463.12704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768289PMC
October 2019

Fate decision of satellite cell differentiation and self-renewal by miR-31-IL34 axis.

Cell Death Differ 2020 03 22;27(3):949-965. Epub 2019 Jul 22.

State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing, 100193, China.

Quiescent satellite cells (SCs) that are activated to produce numerous myoblasts underpin the complete healing of damaged skeletal muscle. How cell-autonomous regulatory mechanisms modulate the balance among cells committed to differentiation and those committed to self-renewal to maintain the stem cell pool remains poorly explored. Here, we show that miR-31 inactivation compromises muscle regeneration in adult mice by impairing the expansion of myoblasts. miR-31 is pivotal for SC proliferation, and its deletion promotes asymmetric cell fate segregation of proliferating cells, resulting in enhanced myogenic commitment and re-entry into quiescence. Further analysis revealed that miR-31 posttranscriptionally suppresses interleukin 34 (IL34) mRNA, the protein product of which activates JAK-STAT3 signaling required for myogenic progression. IL34 inhibition rescues the regenerative deficiency of miR-31 knockout mice. Our results provide evidence that targeting miR-31 or IL34 activities in SCs could be used to counteract the functional exhaustion of SCs in pathological conditions.
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http://dx.doi.org/10.1038/s41418-019-0390-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206105PMC
March 2020

Overexpression of miR-29 Leads to Myopathy that Resemble Pathology of Ullrich Congenital Muscular Dystrophy.

Cells 2019 05 15;8(5). Epub 2019 May 15.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Science, China Agricultural University, Beijing 100193, China.

Ullrich congenital muscular dystrophy (UCMD) bring heavy burden to patients' families and society. Because the incidence of this disease is very low, studies in patients are extremely limited. Animal models of this disease are indispensable. UCMD belongs to extracellular matrix-related diseases. However, the disease models constructed by knocking out some pathogenic genes of human, such as the or gene, of mice could not mimic UCMD. The purpose of this study is to construct a mouse model which can resemble the pathology of UCMD. miR-29 is closely related to extracellular matrix deposition of tissues and organs. To address this issue, we developed a mouse model for overexpression miR-29 using Tet-on system. In the muscle-specific miR-29ab1 cluster transgenic mice model, we found that mice exhibited dyskinesia, dyspnea, and spinal anomaly. The skeletal muscle was damaged and regenerated. At the same time, we clarify the molecular mechanism of the role of miR-29 in this process. Different from human, and , target genes of miR-29, are the key pathogenic genes associating with these phenotypes. This mouse model simulates the human clinical and pathological characteristics of UCMD patients and is helpful for the subsequent research and treatment of UCMD.
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http://dx.doi.org/10.3390/cells8050459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562860PMC
May 2019

Ring-polymer molecular dynamics study on rate coefficient of the barrierless OH + CO system at low temperature.

J Chem Phys 2019 Jan;150(4):044307

iChEM, College of Chemistry and Chemical Engineering, Xiamen University, Siming South Road 422, 361005 Xiamen, China.

Based on the recently constructed neural-network potential energy surface [Chen et al., J. Chem. Phys. 138, 221104 (2013)], ring-polymer molecular dynamics (RPMD) calculations are performed to compute rate coefficients of the barrierless OH + CO system at T ≤ 500 K. To recover the barrierless feature, a Lindemann-Hinshelwood-type mechanism and hence a reduced rate coefficient are used to approximate the overall rate coefficient. An agreement between RPMD and experimental rate coefficients can be found. These RPMD results reproduce correctly the temperature-independence of the overall rate coefficient. Finally, potential sources of errors in the present RPMD calculations are discussed.
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http://dx.doi.org/10.1063/1.5065657DOI Listing
January 2019

A study of anti-gliadin antibodies in first-episode patients with schizophrenia among a Chinese population.

Psychiatry Res 2019 02 29;272:454-457. Epub 2018 Dec 29.

Laboratory for Nursing Science & Institute of Laboratory Medicine, Guangdong Medical University, No.1 Xincheng Road, Dongguan 523808, China. Electronic address:

A recent study suggested that digestion-resistant peptides derived from wheat gluten (mainly gliadin) could induce the secretion of anti-gliadin IgG antibodies in patients with schizophrenia. This research was then designed to replicate this initial finding in 134 drug-naïve patients with first-episode schizophrenia and 160 healthy controls. An enzyme-linked immunosorbent assay was developed in-house with 8 gliadin-derived peptide antigens to test anti-gliadin IgG antibodies in the circulation. The results showed that schizophrenia patients had significantly higher levels of plasma anti-AL2G2 IgG and anti-ABO3a IgG than healthy controls. Based on the specificity of 95%, anti-AL2G2 IgG assay had a sensitivity of 12.7% and anti-ABO3a IgG assay had a sensitivity of 17.2% for anti-ABO3a IgG assay. Increased levels of anti-AL2G2 and anti-ABC3a IgG antibodies were not correlated with total IgG levels in either the patient group or the control group. In conclusion, circulating IgG against AL2G2 and ABO3a may be useful biomarkers for identification of a gluten-sensitive subgroup of schizophrenia in the Chinese population although the present results are rather different from the work performed in a British population.
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http://dx.doi.org/10.1016/j.psychres.2018.12.161DOI Listing
February 2019

Melatonin Improves Parthenogenetic Development of Vitrified⁻Warmed Mouse Oocytes Potentially by Promoting G1/S Cell Cycle Progression.

Int J Mol Sci 2018 Dec 13;19(12). Epub 2018 Dec 13.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu-611130, China.

This study aimed to investigate the effect of melatonin on the cell cycle of parthenogenetic embryos derived from vitrified mouse metaphase II (MII) oocytes. Fresh oocytes were randomly allocated into three groups: untreated (control), or vitrified by the open-pulled straw method without (Vitrification group) or with melatonin (MT) supplementation (Vitrification + MT group). After warming, oocytes were parthenogenetically activated and cultured in vitro, then the percentage of embryos in the G1/S phase, the levels of reactive oxygen species (ROS) and glutathione (GSH), and the mRNA expression of cell cycle-related genes (, and ) in zygotes and their subsequent developmental potential in vitro were evaluated. The results showed that the vitrification/warming procedures significantly decreased the frequency of the S phase, markedly increased ROS and GSH levels and the expression of and genes, and decreased expression in zygotes at the G1 stage and their subsequent development into 2-cell and blastocyst stage embryos. However, when 10 mol/L MT was administered for the whole duration of the experiment, the frequency of the S phase in zygotes was significantly increased, while the other indicators were also significantly improved and almost recovered to the normal levels shown in the control. Thus, MT might promote G1-to-S progression via regulation of ROS, GSH and cell cycle-related genes, potentially increasing the parthenogenetic development ability of vitrified⁻warmed mouse oocytes.
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http://dx.doi.org/10.3390/ijms19124029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321189PMC
December 2018
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