Xiaofang Sun

West China Medical Center of Sichuan University

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Yong Fan

Third Affiliated Hospital of Guangzhou Medical University

Yingjun Xie

Third Affiliated Hospital of Guangzhou Medical University

Bing Song

Jinzhou Medical University

Weiqiang Liu

Nanjing University of Aeronautics and Astronautics

Xinjie Chen

Chinese Academy of Medical Sciences & Peking Union Medical College

Ding Wang

Chinese Academy of Medical Sciences & Peking Union Medical College

Diyu Chen

Third Affiliated Hospital of Guangzhou Medical University

Huimin Zhang

Chinese Academy of Sciences

Daolin Tang

The University of Texas Southwestern Medical Center

Yumei Luo

First Affiliated Hospital of Xi'an Jiaotong University

Cooperative Institutions

Guangzhou Medical University

271

Third Affiliated Hospital of Guangzhou Medical University

198

Chinese Academy of Sciences

169

Chinese Academy of Medical Sciences & Peking Union Medical College

124

Shanghai Jiao Tong University

118

Sun Yat-sen University

113

Peking University

University of Chinese Academy of Sciences

Fudan University

Nanjing Medical University

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Posttranslational modification of autophagy-related proteins in macroautophagy

Autophagy (2014)

Yangchun Xie Rui Kang Xiaofang Sun Meizuo Zhong Jin Huang

Macroautophagy is an intracellular catabolic process involved in the formation of multiple membrane structures ranging from phagophores to autophagosomes and autolysosomes. Dysfunction of macroautophagy is implicated in both physiological and pathological conditions. To date, 38 autophagy-related (ATG) genes have been identified as controlling these complicated membrane dynamics during macroautophagy in yeast; approximately half of these genes are clearly conserved up to human, and there are additional genes whose products function in autophagy in higher eukaryotes that are not found in yeast. The function of the ATG proteins, in particular their ability to interact with a number of macroautophagic regulators, is modulated by posttranslational modifications (PTMs) such as phosphorylation, glycosylation, ubiquitination, acetylation, lipidation, and proteolysis. In this review, we summarize our current knowledge of the role of ATG protein PTMs and their functional relevance in macroautophagy. Unraveling how these PTMs regulate ATG protein function during macroautophagy will not only reveal fundamental mechanistic insights into the regulatory process, but also provide new therapeutic targets for the treatment of autophagy-associated diseases.

Lipid-anchored protein

ATG8

BAG3

10.4161/15548627.2014.984267

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Citations (289)

A Modified Culture Medium Increases Blastocyst Formation and the Efficiency of Human Embryonic Stem Cell Derivation from Poor-Quality Embryos

Journal of Reproduction and Development (2010)

Yong Fan Yumei Luo Xinjie Chen Xiaofang Sun

Human embryonic stem cells (HESCs) are defined as self-renewing cells that retain their ability to differentiate into all cell types of the body. They have enormous potential in medical applications and as a model for early human development. There is a need for derivation of new HESC lines to meet emerging requirements for their use in cell replacement therapies, disease modeling, and basic research. Here, we describe a modified culture medium containing human recombinant leukemia inhibitory factor and human basic fibroblast growth factor that significantly increases the number of human blastocysts formed and their quality, as well as the efficiency of HESC derivation from poor-quality embryos. Culturing poor-quality embryos in modified medium resulted in a two-fold increase in the blastocyst formation rate and a seven-fold increase over the derivation efficiency in conventional medium. We derived 15 HESC lines from poor-quality embryos cultured in modified culture medium and two HESC lines from quality embryos cultured in conventional culture medium. All cell lines shared typical human pluripotent stem cell features including similar morphology, normal karyotypes, expression of alkaline phosphatase, pluripotency genes, such as Oct4, and cell surface markers (SSEA-4, TRA-1-60, TRA-1-81), the ability to form teratomas in SCID mice, and the ability to differentiate into cells of three embryonic germ layers in vitro. Our data suggest that poor-quality embryos that have reached the blastocyst stage in our modified culture medium are a robust source for normal HESC line derivation.

Inner cell mass

Chemically defined medium

KOSR

Germ layer

10.1262/jrd.09-225m

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Citations (26)

Genetically humanized pigs exclusively expressing human insulin are generated through custom endonuclease-mediated seamless engineering

Journal of Molecular Cell Biology (2016)

Yi Yang Kepin Wang Han Wu Qin Jin Degong Ruan

Humanized mouse

Genetically engineered

Homing endonuclease

10.1093/jmcb/mjw008

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Citations (47)

Efficient gene correction of an aberrant splice site in β‐thalassaemia iPSCs by CRISPR/Cas9 and single‐strand oligodeoxynucleotides

Journal of Cellular and Molecular Medicine (2019)

Zeyu Xiong Yingjun Xie Yi Yang Yanting Xue Ding Wang

Abstract β‐thalassaemia is a prevalent hereditary haematological disease caused by mutations in the human haemoglobin β (HBB) gene. Among them, the HBB IVS2‐654 (C > T) mutation, which is in the intron, creates an aberrant splicing site. Bone marrow transplantation for curing β‐thalassaemia is limited due to the lack of matched donors. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9), as a widely used tool for gene editing, is able to target specific sequence and create double‐strand break (DSB), which can be combined with the single‐stranded oligodeoxynucleotide (ssODN) to correct mutations. In this study, according to two different strategies, the HBB IVS2‐654 mutation was seamlessly corrected in iPSCs by CRISPR/Cas9 system and ssODN. To reduce the occurrence of secondary cleavage, a more efficient strategy was adopted. The corrected iPSCs kept pluripotency and genome stability. Moreover, they could differentiate normally. Through CRISPR/Cas9 system and ssODN, our study provides improved strategies for gene correction of β‐Thalassaemia, and the expression of the HBB gene can be restored, which can be used for gene therapy in the future.

10.1111/jcmm.14669

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Baicalein Protects Against Iron Overload Induced Liver Dysfunction in Thalassemic Mice

Journal of Biomedical Nanotechnology (2023)

Weimin Fan Diyu Chen Yinghong Yang Lifen Zhu Feng Yao

Liver iron overload is a common and serious organ injury in β -thalassemia patients. Ferroptosis has been shown to play a crucial role in the pathological injury in iron overloaded hepatocytes. In our study, we focused on the protective effects of baicalein, a natural, active flavone extracted from an herb used in traditional Chinese medicine against RSL3-induced ferroptosis in hepatocytes and high iron diet (HID) induced liver iron-overload in a murine β 654 -thalassemia model. In vitro , the effects of baicalein on RSL3-induced hepatocyte ferroptosis were examined by testing ferroptosis related genes, protein, and the GSH, MDA, iron ion level by RT-PCR, Western blot and the commercial kits respectively. The anti-iron overload injury effects of baicalein were assessed in a β 654 -thalassemia mouse model of high iron diet induced liver injury by the same method In vitro experiments. Here, we found that baicalein could reverse cell ferroptosis in hepatocytes treated with RSL3. Importantly, changes in the iron ion content, and MDA and GSH levels in β 654 -thalassemia mouse livers were significantly restored by baicalein. Mechanistically, baicalein may activated the NRF2 antioxidant pathway and increased the expression of GPX4 in vivo and In vitro . We concluded that baicalein is a potential therapeutic drug for the treatment of iron overload in β -thalassemia.

Baicalein

10.1166/jbn.2023.3642

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The association between sperm head elongation and semen quality

Andrology (2019)

F. Chen Liang Gao Hua Zhou Liyuan Guo Q. Chen

Previous studies suggested that sperm head shape may serve as an effective indicator of semen quality. However, there lacks research with large sample and quantitative measurement.The objective of this retrospective study was to explore the association between sperm head elongation (Width/Length ratio) and routine semen parameters.From January 2012 to December 2017, 63 866 semen samples were collected from male subjects at 18-60 years of age. Sperm head elongation and routine semen parameters (semen volume, sperm concentration, motility, etc.) were examined with computer-assisted semen analysis (CASA) systems in order to evaluate the association between elongation and semen quality.Logistic and linear regression models showed that the value of elongation is negatively correlated with sperm concentration, total sperm count, progressive motility, total motility, percentage of morphologically normal spermatozoa, and acrosin activity (all p < 0.001).The results suggested that higher value of elongation is generally associated with higher risks of abnormality in semen quality. The importance of elongation may be explained by abnormal acrosin activity in the round-headed spermatozoa, which has been reported to cause failure of natural pregnancy.This study provides a new insight into the sperm head shape, which may be used as a complementary parameter in clinical semen examination and academic research.

Semen quality

Semen Analysis

10.1111/andr.12619

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Citations (8)

MicroRNA-141 regulates the tumour suppressor DLC1 in colorectal cancer

Neoplasma (2015)

Pingping Wu Hua Zhu Xiaofang Sun L. X. CHEN Q-S Zhou

Our previous study has showed that DLC1 acts as a functional tumor suppressor in colorectal cancer (CRC) cell lines. The aims of this study were to determine whether DLC1 is a target of MicroRNA (miRNA) regulation and to evaluate the role of this mechanism in CRC. By bioinformatics approach and literature, miR-141 was chosen for further study. The miR-141 mimic, miR-141 inhibitor were synthesized and transfected to Lovo cells. Cell growth was determined by MTT and in vivo models. The flow cytometric analysis for cell cycle determination and transwell assays for evaluating the cell invasion were used. Luciferase reporter assays and Western blots showed that DLC1 was a direct target of miR-141 in CRC. The expression levels of miR-141 were obviously up-regulated in CRC tissues compared to non-cancerous tissues, while DLC1 expression levels were down-regulated in a high proportion of clinical samples (14/18). In addition, correlation analyses revealed negative correlation between miR-141 levels and DLC1 expression levels in CRC tissues. MiR-141 overexpression promoted cell growth in vitro and in vivo, promoted cell cycle progression and invasion in Lovo cells. Furthermore, re-introduction of DLC-1 in miR-141-overexpressing Lovo cells decreased growth rate of cells, increase of the percentage in G0/G1 phase and decreased the number of migrating cells. In conclusion, we demonstrated that miR-141 is up-regulated in CRC and acts as a functional oncogene by targeting DLC1.

MTT assay

10.4149/neo_2015_084

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Citations (33)

Human embryonic stem cell lines are contaminated: what should we do?

Human Reproduction (2005)

Weihua Wang Xiaofang Sun

Human embryonic stem (hES) cells have the potential to differentiate into any desired cells and to be used in cell replacement therapies for some diseases. However, existing hES cell lines would not be suitable for the therapies as they are contaminated with other biological products. In order to produce the safest hES cell lines for therapeutic purposes, all steps for the establishment of hES cell lines must avoid the use of animal serum and/or animal feeder cell lines. Safe and fast approaches to producing hES cell lines based on recent research advances in both humans and animals have been suggested.

10.1093/humrep/dei197

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Citations (9)

Comparison between laparoscopic sleeve gastrectomy and laparoscopic adjustable gastric banding for morbid obesity

国际外科学杂志 (2013)

Sen Wang Xiaofang Sun

Objective To compare the effects of laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB) on excess weight loss (EWL) and type 2 diabetes mellitus (T2DM),then to evaluate which one is superior to the other.Methods PubMed,Embase,Wanfang Database and HowNet database were searched for publications concerning LAGB and LSG from 2000 to 2012,with the last search on August 17,2012.EWL and T2DM improvement over 6 and 12 months were pooled and compared by meta-analysis.Odds ratios (ORs) and mean differences were calculated with 95％ confidence intervals （ CI).Results Eleven studies involving 1004 patients in total met the inclusion criteria.The mean percentage EWL for LAGB was 33.9％ after 6 months in studies and 37.8％ after 12 months; for LSG,EWL was 50.6％ after 6 months and 51.8％ after 12 months,T2DM was improved in 42 of 68 patients (61.8％) after LAGB and 66 of 80 (82.5％) after LSG.Conclusions LSG is more effective than LAGB in morbid obesity,with higher percentage EWL and greater improvement in T2DM. Key words: Laparoscopic sleeve gastrectomy; Laparoscopic adjustable gastric banding; Diabetes mellitus, type 2; Obesity, morbid; Bariatric surgery; Treatment outcome

Excess weight

Sleeve gastrectomy

Gastric banding

10.3760/cma.j.issn.1673-4203.2013.10.005

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DNA Microarray Reveals That High Proportions of Human Blastocysts from Women of Advanced Maternal Age Are Aneuploid and Mosaic1

Biology of Reproduction (2012)

Jianqiao Liu Wei‐Hua Wang Xiaofang Sun Lian Liu Hua Jin

Trophectoderm (TE) biopsy and DNA microarray have become the new technologies for preimplantation genetic diagnosis in humans. In this study, we comprehensively examined aneuploid formation in human blastocysts produced in vitro with microarray and investigated the clinical outcome after transfer of euploid embryos. Biopsied cells from either TE or inner cell mass (ICM) were processed for microarray to examine the errors in 23 pairs of chromosomes and the consistency between TE and ICM. It was found that 56.6% of blastocysts were aneuploid. Further analysis indicated that 62.3% of aneuploid blastocysts had single and 37.7% had multiple chromosomal abnormalities. Chromosome errors could occur in any chromosome, but errors in chromosome 21 accounted for the most (11.3%) among the 23 pairs of chromosomes. Transfer of array-screened blastocysts produced high pregnancy (70.2%) and implantation (63.5%) rates. Microarray of TE and ICM cells in the same blastocysts revealed that high proportions of aneuploid blastocysts (69.2%) were mosaic, including aneuploid TE and euploid ICM, inconsistent anomalies between ICM and TE, or euploid TE cells and aneuploid ICM in the same blastocyst. These results indicate that high proportions of human blastocysts produced in vitro from women of advanced maternal age are aneuploid and mosaic. Errors can occur in any of the 23 pairs of chromosomes in human blastocysts. Biopsy from TE in blastocysts does not exactly predict the chromosomal information in ICM if the embryos are aneuploid. Some mosaic blastocysts have euploid ICM, which may indicate important differentiate mechanism(s) of human preimplantation embryos.

Inner cell mass

10.1095/biolreprod.112.103192

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Citations (99)