Publications by authors named "Xiaohang Yang"

50 Publications

Renal interstitial fibrosis is reduced in high-fat diet-induced obese pigs following renal denervation from the intima and adventitia of the renal artery.

Kidney Blood Press Res 2021 Dec 1. Epub 2021 Dec 1.

Background This study aims to compare whether two different routes of Renal denervation (RDN) from the intima and adventitia of the renal artery can reduce renal fibrosis in a pig model of hypertension induced by a high-fat diet and to explore possible molecular mechanisms. Methods Twenty-four Bama miniature pigs were randomly divided into a control group (normal diet, n=6) or a hypertension model group (high-fat diet, n=18). The model group was randomly divided into the intima-RDN group (n=6), the adventitia-RDN group (n=6), or the renal arteriography only group (sham group, n=6). All animals were fed separately. The model group was fed a high-fat diet after the operation, and the control group was fed conventionally for 6 months. After 6 months, renal artery angiography was performed again to observe the condition of the renal arteries, after which all animals were euthanized. The blood pressure (BP) and blood biochemical results of each group were evaluated 6 months after the operation; kidney tissue morphology and collagen fiber content were examined by hematoxylin-eosin (HE) staining and Masson staining; Superoxide dismutase (SOD) activity and the malondialdehyde (MDA) content of kidney tissue were assessed by a biochemical enzyme method; the protein expression level of transforming growth factor-β 1 (TGF-β1), α smooth muscle actin (αSMA) and Smad3 were assessed by Western blot; and electron microscopy was used to examine changes in kidney microstructure. Results After 6 months of a high-fat diet, the blood lipid levels of the model group were significantly higher compared to baseline and to that of the control group during the same period (all showed P<0.05); the blood lipid levels of the control group did not change significantly from baseline (P>0.05). The degree of glomerular damage caused by hyperlipidemia in the intima-RDN group and the adventitia-RDN group was significantly lower than that of the sham and control groups, and the renal fibrosis area percentage was also significantly lower (P<0.05). Electron microscopy showed that both the intima-RDN group and the adventitia-RDN group had a more even distribution of chromosomes and less mitochondrial swelling compared with the sham group. Conclusion RDN from the adventitia of the renal artery and RDN from the intima of the renal artery have the similar advantages of delaying high fat-induced renal fibrosis. The anti-fibrotic effect of RDN may be related to inhibition of the TGF-β1/smad3 pathway.
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http://dx.doi.org/10.1159/000521100DOI Listing
December 2021

Implications of Isolated Para-Aortic Lymph Node Metastasis in Endometrial Cancer: A Large-Scale, Multicenter, and Retrospective Study.

Front Med (Lausanne) 2021 21;8:754890. Epub 2021 Oct 21.

Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

To systematically evaluate lymph node metastasis (LNM) patterns in patients with endometrial cancer (EC) who underwent complete surgical staging, which included systematic pelvic and para-aortic lymphadenectomy. Four thousand and one patients who underwent complete surgical staging including systematic pelvic and para-aortic lymphadenectomy for EC were enrolled from 30 centers in China from 2001 to 2019. We systematically displayed the clinical and prognostic characteristics of patients with various LNM patterns, especially the PLN-PAN+ [para-aortic lymph node (PAN) metastasis without pelvic lymph node (PLN) metastasis]. The efficacy of PAN+ (para-aortic lymph node metastasis) prediction with clinical and pathological features was evaluated. Overall, 431 of the 4,001 patients (10.8%) showed definite LNM according to pathological diagnosis. The PAN+ showed the highest frequency (6.6%) among all metastatic sites. One hundred fourteen cases (26.5%) were PLN-PAN+ (PAN metastasis without PLN metastasis), 167 cases (38.7%) showed PLN+PAN-(PLN metastasis without PAN metastasis), and 150 cases (34.8%) showed metastasis to both regions (PLN+PAN+). There was also 1.9% (51/2,660) of low-risk patients who had PLN-PAN+. There are no statistical differences in relapse-free survival (RFS) and disease-specific survival (DSS) among PLN+PAN-, PLN-PAN+, and PLN+PAN+. The sensitivity of gross PLNs, gross PANs, and lymphovascular space involvement (LVSI) to predict PAN+ was 53.8 [95% confidence interval (CI): 47.6-59.9], 74.2 95% CI: 65.6-81.4), and 45.8% (95% CI: 38.7-53.2), respectively. Over one-fourth of EC patients with LMN metastases were PLN-PAN+. PLN-PAN+ shares approximate survival outcomes (RFS and DSS) with other LNM patterns. No effective clinical methods were achieved for predicting PAN+. Thus, PLN-PAN+ is a non-negligible LNM pattern that cannot be underestimated in EC, even in low-risk patients.
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http://dx.doi.org/10.3389/fmed.2021.754890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566710PMC
October 2021

The S100A10-AnxA2 complex is associated with the exocytosis of hepatitis B virus in intrauterine infection.

Lab Invest 2021 Oct 13. Epub 2021 Oct 13.

The Women's Hospital, Zhejiang University School of Medicine, No. 1 Xueshi Road, Shangcheng District, Hangzhou, Zhejiang, 310001, China.

Mother-to-child transmission (MTCT) is the major cause of chronic infection of hepatitis B virus (HBV) in patients. However, whether and how HBV crosses the placenta to cause infection in utero remains unclear. In this study, we investigate the mechanism as to how the HBV virions pass through layers of the trophoblast. Our data demonstrate the exocytosis of virions from the trophoblast after exposure to HBV where the endocytosed HBV virions co-localized with an S100A10/AnxA2 complex and LC3, an autophagosome membrane marker. Knockdown of either AnxA2 or S100A10 in trophoblast cells led to a reduction of the amount of exo-virus in Transwell assay. Immunohistochemistry also showed a high expression of AnxA2 and S100A10 in the placental tissue samples of HBV-infected mothers with congenital HBV-positive infants (HBV). We conclude that in HBV intrauterine infection and mother-to-child transmission, a proportion of HBV hijacks autophagic protein secretion pathway and translocate across the trophoblast via S100A10/AnxA2 complex and multivesicular body (MVB)-mediated exocytosis. Our study provides a potential target for the interference of the mechanisms of HBV intrauterine infection and mother-to-child transmission.
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http://dx.doi.org/10.1038/s41374-021-00681-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512653PMC
October 2021

The Exploration of Poor Ovarian Response-Related Risk Factors: A Potential Role of Growth Differentiation Factor 8 in Predicting Ovarian Response in IVF-ET Patient.

Front Endocrinol (Lausanne) 2021 24;12:708089. Epub 2021 Sep 24.

Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Controlled ovarian hyperstimulation (COH) is the most common therapeutic protocol to obtain a considerable number of oocytes in IVF-ET cycles. To date, the risk factors affecting COH outcomes remain elusive. Growth differentiation factor 8 (GDF-8), a member of transforming growth factor β (TGF-β) superfamily, has been long discerned as a crucial growth factor in folliculogenesis, and the aberrant expression of GDF-8 is closely correlated with the reproductive diseases. However, less is known about the level of GDF-8 in IVF-ET patients with different ovarian response. In the present study, the potential risk factors correlated with ovarian response were explored using logistic regression analysis methods. Meanwhile, the expression changes of GDF-8 and its responsible cellular receptors in various ovarian response patients were determined. Our results showed that several factors were intensely related to poor ovarian response (POR), including aging, obesity, endometriosis, surgery history, and IVF treatment, while irregular menstrual cycles and PCOS contribute to hyperovarian response (HOR). Furthermore, POR patients exhibited a decrease in numbers of MII oocytes and available embryos, thereby manifesting a lower clinical pregnancy rate. The levels of GDF-8, ALK5, and ACVR2B in POR patients were higher compared with those in control groups, whereas the expression level of ACVR2A decreased in poor ovarian response patients. In addition, clinical correlation analysis results showed that the concentration of GDF-8 was negatively correlated with LH and estradiol concentration and antral follicle count. Collectively, our observations provide a novel insight of ovarian response-associated risk factors, highlighting the potential role of GDF-8 levels in ovarian response during COH process.
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http://dx.doi.org/10.3389/fendo.2021.708089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499678PMC
September 2021

Transcriptome-Based Analysis Reveals Therapeutic Effects of Resveratrol on Endometriosis in aRat Model.

Drug Des Devel Ther 2021 29;15:4141-4155. Epub 2021 Sep 29.

The Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, People's Republic of China.

Introduction: Endometriosis (EMs) is associated with severe chronic pelvic pain and infertility and the development of improved EMs treatment options is an ongoing focus. In this study, we investigated the effects of resveratrol on EMs and analyzed transcriptional changes in the lesions of model rats before and after resveratrol treatment.

Methods: We established arat model of endometriosis through the trans-implantation of endometrial fragments to the peritoneal wall and then used resveratrol as treatment. We then analyzed the results using RNA sequencing of the lesion tissues of each of the model rats before resveratrol treatment and the reduced lesion tissues after the treatment. Examinations of anatomy, biochemistry, immunohistochemical staining and flow cytometry examinations were also conducted. Other trans-implanted rats were also given sham treatments as sham-treatment control and other untrans-implanted rats served as sham-operation controls.

Results: In addition to the obvious lesions observed in the model rats, there were significant differences in the glucose tolerance, macrophage M1/M2 polarization, and adipocyte sizes between the treated model rats and sham (control) rats. Resveratrol treatment in the model rats showed significant efficacy and positive therapeutic effect. Transcriptional analysis showed that the effects of resveratrol on the endometriosis model rats were manifested by alterations in the PPAR, insulin resistance, MAPK and PI3K/Akt signaling pathways. Correspondingly, changes in PPARγ activation, M1/M2 polarization and lipid metabolism were also detected after resveratrol treatment.

Discussion: Our study revealed that resveratrol treatment displayed efficient therapeutic effects for EMs model rats, probably through its important roles in anti-inflammation, immunoregulation and lipid-related metabolism regulation.
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http://dx.doi.org/10.2147/DDDT.S323790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487867PMC
September 2021

Lipidomic Alterations and PPAR Activation Induced by Resveratrol Lead to Reduction in Lesion Size in Endometriosis Models.

Oxid Med Cell Longev 2021 11;2021:9979953. Epub 2021 Sep 11.

The Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China.

Endometriosis is an estrogen-dependent chronic inflammatory disease that affects approximately 10% of women of reproductive age and up to 50% of women with infertility. The heterogeneity of the disease makes accurate diagnosis and treatment a clinical challenge. In this study, we generated two models of endometriosis: the first in rats and the second using human ectopic endometrial stromal cells (HEcESCs) derived from the lesion tissues of endometriosis patients. We then applied resveratrol to assess its therapeutic potential. Resveratrol intervention had significant efficacy to attenuate lesion size and to rectify aberrant lipid profiles of model rats. Lipidomic analysis revealed significant lipidomic alterations, including notable increases of sphingolipids and decreases of both glycerolipids and most phospholipids. Upon resveratrol application, both proliferation capacity and invasiveness parameters decreased, and the early apoptosis proportion increased for HEcESCs. The activation of PPAR was also noted as a factor potentially contributing to recovery from endometriosis in both models. Our study provides valuable insight into the mechanisms of resveratrol in endometriosis and therefore strengthens the potential for optimizing resveratrol treatment for this disease.
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http://dx.doi.org/10.1155/2021/9979953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452402PMC
September 2021

Role of Cofilin in Alzheimer's Disease.

Front Cell Dev Biol 2020 26;8:584898. Epub 2020 Nov 26.

College of Acupuncture and Massage, Shaanxi University of Chinese Medicine, Xianyang, China.

Alzheimer's disease (AD) is a degenerative neurological disease and has an inconspicuous onset and progressive development. Clinically, it is characterized by severe dementia manifestations, including memory impairment, aphasia, apraxia, loss of recognition, impairment of visual-spatial skills, executive dysfunction, and changes in personality and behavior. Its etiology is unknown to date. However, several cellular biological signatures of AD have been identified such as synaptic dysfunction, β-amyloid plaques, hyperphosphorylated tau, cofilin-actin rods, and Hirano bodies which are related to the actin cytoskeleton. Cofilin is one of the most affluent and common actin-binding proteins and plays a role in cell motility, migration, shape, and metabolism. They also play an important role in severing actin filament, nucleating, depolymerizing, and bundling activities. In this review, we summarize the structure of cofilins and their functional and regulating roles, focusing on the synaptic dysfunction, β-amyloid plaques, hyperphosphorylated tau, cofilin-actin rods, and Hirano bodies of AD.
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http://dx.doi.org/10.3389/fcell.2020.584898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726191PMC
November 2020

The conserved microRNA miR-210 regulates lipid metabolism and photoreceptor maintenance in the Drosophila retina.

Cell Death Differ 2021 02 10;28(2):764-779. Epub 2020 Sep 10.

Division of Human Reproduction and Developmental Genetics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.

Increasing evidence suggests that miRNAs play important regulatory roles in the nervous system. However, the molecular mechanisms of how specific miRNAs affect neuronal development and functions remain less well understood. In the present study, we provide evidence that the conserved microRNA miR-210 regulates lipid metabolism and prevents neurodegeneration in the Drosophila retina. miR-210 is specifically expressed in the photoreceptor neurons and other sensory organs. Genetic deletion of miR-210 leads to lipid droplet accumulation and photoreceptor degeneration in the retina. These effects are associated with abnormal activation of the Drosophila sterol regulatory element-binding protein signaling. We further identify the acetyl-coenzyme A synthetase (ACS) as one functionally important target of miR-210 in this context. Reduction of ACS in the miR-210 mutant background suppresses the neurodegeneration defects, suggesting that miR-210 acts through regulation of the ACS transcript. Together, these results reveal an unexpected role of miR-210 in controlling lipid metabolism and neuronal functions.
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http://dx.doi.org/10.1038/s41418-020-00622-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862623PMC
February 2021

Laparoscopic-based perivascular renal sympathetic nerve denervation: a feasibility study in a porcine model.

Eur J Med Res 2020 Jun 18;25(1):22. Epub 2020 Jun 18.

Department of Cardiology, Zhengzhou University People's Hospital, Zhengzhou, 450003, People's Republic of China.

Background: This study aims to evaluate the effects and safety of laparoscopic-based perivascular renal sympathetic nerve denervation (RDN) in a porcine model fed a high-fat diet.

Method: Thirty-six high-fat diet-fed Bama minipigs were randomly divided into an RDN group (n = 18), in which minipigs received laparoscopic-based perivascular RDN, and a sham group (n = 18). All pigs were fed the high-fat diet after the operation to establish a model of obesity-induced hypertension. Bama pigs in the RDN and sham groups were killed at 3 time points [2 days after RDN (n = 6), day 90 (n = 6) and day 180 (n = 6)].

Result: The systolic blood pressure (SBP) and noradrenaline (NE) concentration in the kidney tissue were significantly lower in the RDN group than in the sham group at 2 days (113.83 ± 3.26 mmHg vs 129.67 ± 3.32 mmHg, P = 0.011, and 112.02 ± 17.34 ng/g vs 268.48 ± 20.61 ng/g, P < 0.001, respectively), 90 days (116.83 ± 3.88 mmHg vs 145.00 ± 4.22 mmHg, P = 0.001, respectively) and 180 days (129.33 ± 2.87 mmHg vs 168.57 ± 2.86 mmHg, P < 0.001, and 152.15 ± 16.61 ng/g vs 318.97 ± 24.84 ng/g, P < 0.001, respectively) after the operation. The diastolic blood pressure (DBP) was significantly lower in the RDN group than in sham group at 90 and 180 days after the operation (72.17 ± 2.7 mmHg vs 81.50 ± 2.22 mmHg, P = 0.037, and 76.83 ± 2.75 mmHg vs 86.33 ± 2.22 mmHg P = 0.021, respectively). Based on the pathological evaluation, the renal sympathetic nerve fascicles were successfully disrupted by radiofrequency energy after laparoscopic-based perivascular RDN, but the intima was intact. Tyrosine hydroxylase (TH) expression was decreased, while the expression of the S100 protein was increased in treated renal arteries after RDN.

Conclusions: Laparoscopic-based perivascular RDN prevented the occurrence and development of hypertension, and thus it may be an efficient and safe method for controlling blood pressure in an experimental model.
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http://dx.doi.org/10.1186/s40001-020-00422-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301974PMC
June 2020

A motor neuron protective role of miR-969 mediated by the transcription factor kay.

RNA Biol 2020 09 13;17(9):1277-1283. Epub 2020 May 13.

Division of Human Reproduction and Developmental Genetics, Women's Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, China.

Maintenance of motor neuron structure and function is crucial in development and motor behaviour. However, the genetic regulatory mechanism of motor neuron function remains less well understood. In the present study, we identify a novel neuroprotective role of the microRNA miR-969 in motor neurons. miR-969 is highly expressed in motor neurons. Loss of miR-969 results in early-onset and age-progressive locomotion impairment. Flies lacking miR-969 also exhibit shortened lifespan. Moreover, miR-969 is required in motor neurons. We further identify kay as a functionally important target of miR-969. Together, our results indicate that miR-969 can protect motor neuron function by limiting kay activity in .
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http://dx.doi.org/10.1080/15476286.2020.1757897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549711PMC
September 2020

Aggravated endothelial endocrine dysfunction and intimal thickening of renal artery in high-fat diet-induced obese pigs following renal denervation.

BMC Cardiovasc Disord 2020 04 16;20(1):176. Epub 2020 Apr 16.

Department of Cardiology, Zhengzhou University People's Hospital, No.7 Weiwu road, Jinshui District, Zhengzhou, 450003, Henan, China.

Background: Renal denervation (RDN) targeting the sympathetic nerves in the renal arterial adventitia as a treatment of resistant hypertension can cause endothelial injury and vascular wall injury. This study aims to evaluate the risk of atherosclerosis induced by RDN in renal arteries.

Methods: A total of 15 minipigs were randomly assigned to 3 groups: (1) control group, (2) sham group, and (3) RDN group (n = 5 per group). All pigs were fed a high-fat diet (HFD) for 6 months after appropriate treatment. The degree of intimal thickening of renal artery and the conversion of endothelin 1 (ET-1) receptors were evaluated by histological staining. Western blot was used to assess the expression of nitric oxide (NO) synthesis signaling pathway, ET-1 and its receptors, NADPH oxidase 2 (NOX2) and 4-hydroxynonenal (4-HNE) proteins, and the activation of NF-kappa B (NF-κB).

Results: The histological staining results suggested that compared to the sham treatment, RDN led to significant intimal thickening and significantly promoted the production of endothelin B receptor (ETR) in vascular smooth muscle cells (VSMCs). Western blotting analysis indicated that RDN significantly suppressed the expression of AMPK/Akt/eNOS signaling pathway proteins, and decreased the production of NO, and increased the expression of endothelin system proteins including endothelin-1 (ET-1), endothelin converting enzyme 1 (ECE1), endothelin A receptor (ETR) and ETR; and upregulated the expression of NOX2 and 4-HNE proteins and enhanced the activation of NF-kappa B (NF-κB) when compared with the sham treatment (all p < 0.05). There were no significant differences between the control and sham groups (all p > 0.05).

Conclusions: RDN aggravated endothelial endocrine dysfunction and intimal thickening, and increased the risk of atherosclerosis in renal arteries of HFD-fed pigs.
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http://dx.doi.org/10.1186/s12872-020-01472-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161153PMC
April 2020

Prominin-like, a homolog of CD133, interacts with ND20 to maintain mitochondrial function.

Cell Biosci 2019 19;9:101. Epub 2019 Dec 19.

1College of Life Science, Zhejiang University, Hangzhou, 310058 Zhejiang China.

Background: Prominin-like is a homolog of mammalian CD133, which is recognized as a biomarker for stem cells. The interacting proteins of CD133 and their biological functions remain elusive.

Results: In this study, we using yeast two-hybrid assays, GST pull-down assay and co-immunoprecipitation (Co-IP) methods found that Prominin-like interacts with ND20, a subunit of mitochondrial respiratory complex I. Bioinformatics analysis suggests that Prominin-like is a six-transmembrane glycoprotein which localizes on cellular membranes. Immunostaining and mitochondrial fractionation indicate that Prominin-like could localize in the mitochondria. The knockdown of - in S2 cells resulted in transient mitochondrial dysfunctions as evidenced by reduced ATP production, elevated ROS generation and an accompanied reduction in mitochondrial proteins. Mitochondrial dysfunctions were detected in aged - mutant flies.

Conclusion: Our data indicates that Prominin-like acts to maintain mitochondrial function through its interaction with ND20 which, itself, is active in the mitochondrial electron transport chain. Our study provides insights into a novel molecular mechanism of - and suggests a similar function of CD133 in mammals.
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http://dx.doi.org/10.1186/s13578-019-0365-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923988PMC
December 2019

BRCA mutation frequency and clinical features of ovarian cancer patients: A report from a Chinese study group.

J Obstet Gynaecol Res 2019 Nov 14;45(11):2267-2274. Epub 2019 Aug 14.

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, China.

Aim: Subjects with germline BRCA1/2 mutations (gBRCAm) have an increased risk of developing breast cancer and ovarian cancer. At present, knowledge of BRCA1/2 mutation frequency in Chinese patients with ovarian cancer is still insufficient, and the detailed clinical information of these patients is poorly understood.

Methods: A total of 547 unselected ovarian cancer patients were enrolled, and their gBRCAm status was detected. Clinical characteristics including age, personal and family history, histopathologic diagnosis, carbohydrate antigen 125 (CA-125) level, ascites, Federation International of Gynecology and Obstetrics (FIGO) stage, residual lesions, platinum sensitivity, recurrence interval and survival information were collected. Accurate assessments of disease response were based on the RECIST standard or CA-125 level.

Results: In 547 patients with ovarian cancer, we detected 129 (23.6%) patients with pathogenic mutations, 84 patients with BRCA1 mutations (15.4%) and 45 patients with BRCA2 mutations (8.2%). Twenty-five novel mutations were identified, and the mutation of BRCA1, c.5470_5477del8, was the most common mutation in this study. BRCA1/2 mutations were significantly associated with age; personal and family history; FIGO stage; secondary recurrence interval; sensitivity to platinum in 1st, 2nd and 3rd line treatment; and response to doxorubicin liposomes. Patients with BRCA1/2 mutations showed significant advantages in 3- and 5-year survival rates but no advantage in long-term survival.

Conclusion: BRCA1/2 mutation prevalence in Chinese ovarian cancer patients is higher than the international rate. We recommend BRCA1/2 testing for patients with family histories and personal histories of malignancy and genetic counseling for cancer in healthy people with high-risk family histories.
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http://dx.doi.org/10.1111/jog.14090DOI Listing
November 2019

A Novel Neuroprotective Role of Phosphatase of Regenerating Liver-1 against CO Stimulation in Drosophila.

iScience 2019 Sep 22;19:291-302. Epub 2019 Jul 22.

Institute of Genetics and Department of Genetics, Division of Human Reproduction and Developmental Genetics of the Women's Hospital, Zhejiang University School of Medicine, Yuhangtang Road 866, Xihu District, Hangzhou, Zhejiang Province 310058, China. Electronic address:

Neuroprotection is essential for the maintenance of normal physiological functions in the nervous system. This is especially true under stress conditions. Here, we demonstrate a novel protective function of PRL-1 against CO stimulation in Drosophila. In the absence of PRL-1, flies exhibit a permanent held-up wing phenotype upon CO exposure. Knockdown of the CO olfactory receptor, Gr21a, suppresses the phenotype. Our genetic data indicate that the wing phenotype is due to a neural dysfunction. PRL-1 physically interacts with Uex and controls Uex expression levels. Knockdown of Uex alone leads to a similar wing held-up phenotype to that of PRL-1 mutants. Uex acts downstream of PRL-1. Elevated Uex levels in PRL-1 mutants prevent the CO-induced phenotype. PRL-1 and Uex are required for a wide range of neurons to maintain neuroprotective functions. Expression of human homologs of PRL-1 could rescue the phenotype in Drosophila, suggesting a similar function in humans.
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http://dx.doi.org/10.1016/j.isci.2019.07.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700421PMC
September 2019

Pathological features, clinical presentations and prognostic factors of ovarian large cell neuroendocrine carcinoma: a case report and review of published literature.

J Ovarian Res 2019 Jul 25;12(1):69. Epub 2019 Jul 25.

Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.

Background: There is no consensus on the optimal chemotherapy regimen and the prognostic factors for ovarian large cell neuroendocrine carcinoma (LCNEC), a rare type of tumor. The objective of the present study is to present the case of a recent encounter of pure ovarian LCNEC and perform a brief review to summarize the clinicopathological features and prognostic factors of 57 cases of LCNEC patients that have been previously reported.

Method: CASE PRESENTATION: Eligible studies were searched for online and 57 cases with clear follow-up data were found to have been reported. We present the 58th case, which is of a 70-year-old woman with stage IIIc primary pure LCNEC of the ovary. The initial symptom of this patient was abdominal distension (more than 2 months). A recent ultrasound test showed a solid-cystic mass occupying the pelvic and abdominal cavity. She received two courses of cisplatin-etoposide chemotherapy as an adjuvant therapy. No signs of nonclinical or radiological evidence of disease recurrence was found at follow-up examinations during the first 3 months after operation. A retrospective review of these 58 cases was conducted and survival curves were estimated. Using the Kaplan-Meier method.

Conclusion: The patients included were aged between 18 and 80 years. A Kaplan-Meier survival curve revealed that the median overall survival was 10.000 months, while 26 (44.83%) patients died within 12 months. We compared the overall mean survival time of all patients with that of stage I patients (42.418 vs 42.047 months), which suggests that ovarian LCNEC has a very poor prognosis even at stage I. Mean survival was longer for patients who had undergone postoperative chemotherapy than for those without postoperative chemotherapy (48.082 vs 9.778 months). A small series, such as this, does not provide adequate data to establish a firm correlation between the postoperative chemotherapy and prognosis (p = 0.176). In our review of 58 cases with ovarian LCNEC, prognosis was unfavorable in most cases. Given the rarity of LCNEC, it is highly recommended that a global medical database of ovarian LCNEC and a standard system of diagnosis and treatment is established.
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http://dx.doi.org/10.1186/s13048-019-0543-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657379PMC
July 2019

Acute changes in morphology and renal vascular relaxation function after renal denervation using temperature-controlled radiofrequency catheter.

BMC Cardiovasc Disord 2019 03 22;19(1):67. Epub 2019 Mar 22.

Department of Cardiology, Zhengzhou University People's Hospital, No.7 Weiwu road, Jinshui District, Zhengzhou, 450003, China.

Background: Resistant hypertension and renal sympathetic hyperactivity are closely linked, and catheter-based renal denervation (RDN) is regarded as a new treatment strategy. However, the acute changes in vascular morphology and relaxation function have yet to be evaluated, and these may be important for the efficacy and safety of the procedure. In this study, we explored these questions by conventional temperature-controlled cardiac radiofrequency catheter-based RDN in a pig model.

Methods: Six mini-pigs were randomly divided into the renal denervation (RDN) group (n = 3) and the Sham-RDN group (n = 3). Animals in the RDN group underwent unilateral radiofrequency ablation, and those in the Sham-RDN group underwent the same procedure except for the ablation. The pigs were examined by angiography pre- and post-RDN and were euthanized immediately thereafter. Renal arteries were processed for histological and molecular biology analyses as well as for in vitro vascular tension testing.

Results: Compared with the Sham-RDN group, the RDN caused vascular intima and media injury, renal nerve vacuolization, mild collagen fiber hyperplasia and elastic fiber cleavage (all p < 0.05). The RDN group also significantly exhibited nitric oxide synthase pathway inhibition and decreased endothelium-independent vascular relaxation function Compared to the Sham-RDN group (all p < 0.05).

Conclusions: In this porcine model, renal artery denervation led to vascular wall injury and endothelial dysfunction in the acute phase, which negatively affected vascular relaxation function. Thus, this process may be detrimental to the prognosis and progress of hypertension patients.
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http://dx.doi.org/10.1186/s12872-019-1053-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431051PMC
March 2019

The autophagy-related gene in regulates both neuron and midgut homeostasis.

J Biol Chem 2019 04 13;294(14):5666-5676. Epub 2019 Feb 13.

From the Division of Human Reproduction and Developmental Genetics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China 310058,

is an autophagy-related gene identified in worms, flies, mice, and mammals, which encodes a protein that functions in autophagosome formation by associating with the ULK1-Atg13-Fip200 complex. In the last few years, the critical role of Atg101 in autophagy has been well-established through biochemical studies and the determination of its protein structure. However, Atg101's physiological role, both during development and in adulthood, remains less understood. Here, we describe the generation and characterization of an loss-of-function mutant in and report on the roles of Atg101 in maintaining tissue homeostasis in both adult brains and midguts. We observed that homozygous or hemizygous mutants were semi-lethal, with only some of them surviving into adulthood. Both developmental and starvation-induced autophagy processes were defective in the mutant animals, and mutant adult flies had a significantly shorter lifespan and displayed a mobility defect. Moreover, we observed the accumulation of ubiquitin-positive aggregates in mutant brains, indicating a neuronal defect. Interestingly, mutant adult midguts were shorter and thicker and exhibited abnormal morphology with enlarged enterocytes. Detailed analysis also revealed that the differentiation from intestinal stem cells to enterocytes was impaired in these midguts. Cell type-specific rescue experiments disclosed that Atg101 had a function in enterocytes and limited their growth. In summary, the results of our study indicate that Atg101 is essential for tissue homeostasis in both adult brains and midguts. We propose that Atg101 may have a role in age-related processes.
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http://dx.doi.org/10.1074/jbc.RA118.006069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462509PMC
April 2019

Drosophila Pif1A is essential for spermatogenesis and is the homolog of human CCDC157, a gene associated with idiopathic NOA.

Cell Death Dis 2019 02 11;10(2):125. Epub 2019 Feb 11.

Division of Human Reproduction and Developmental Genetics, the Women's Hospital, Zhejiang University School of Medicine, Yuhangtang Road 866, 310012, Hangzhou, Zhejiang, China.

The dynamic process of spermatogenesis shows little variation between invertebrate models such as Drosophila, and vertebrate models such as mice and rats. In each case, germ stem cells undergo mitotic division to proliferate and then continue, via meiosis, through various stages of elongation and individualization from spermatogonia to spermatid to finally to form mature sperm. Mature sperm are then stored in the seminal vesicles for fertilization. Errors in any of these stages can lead to male infertility. Here, we identify that Drosophila Pif1A acts as a key regulator for sperm individualization. Loss of Pif1A leads to male sterility associated with irregular individualization complex and empty seminal vesicles without mature sperm. Pif1A is highly expressed in the testes of mated male adult flies and the Pif1A protein is expressed at a higher level in male than in female flies. Pif1A is homologous to mammalian coiled-coil domain-containing protein 157 (CCDC157), which is also enriched in the testes of humans and mice. Human CCDC157, with unknown function, was identified to be downregulated in men with idiopathic non-obstructive azoospermia (NOA). We map the function of Drosophila Pif1A during spermatogenesis, showing that Pif1A is essential for spermatide individualization and involved in the regulation of the lipid metabolism genes. Our findings might be applicable for studying the function of CCDC157 in spermatogenesis and other aspects of human male fertility.
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http://dx.doi.org/10.1038/s41419-019-1398-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370830PMC
February 2019

Hcf regulates the Hippo signaling pathway via association with the histone H3K4 methyltransferase Trr.

Biochem J 2019 02 28;476(4):759-768. Epub 2019 Feb 28.

Division of Human Reproduction and Developmental Genetics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China

Control of organ size is a fundamental aspect in biology and plays important roles in development. The Hippo pathway is a conserved signaling cascade that controls tissue and organ size through the regulation of cell proliferation and apoptosis. Here, we report on the roles of Hcf (host cell factor), the homolog of Host cell factor 1, in regulating the Hippo signaling pathway. Loss-of-Hcf function causes tissue undergrowth and the down-regulation of Hippo target gene expression. Genetic analysis reveals that Hcf is required for Hippo pathway-mediated overgrowth. Mechanistically, we show that Hcf associates with the histone H3 lysine-4 methyltransferase Trithorax-related (Trr) to maintain H3K4 mono- and trimethylation. Thus, we conclude that Hcf positively regulates Hippo pathway activity through forming a complex with Trr and controlling H3K4 methylation.
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http://dx.doi.org/10.1042/BCJ20180717DOI Listing
February 2019

RanGAP-mediated nucleocytoplasmic transport of Prospero regulates neural stem cell lifespan in Drosophila larval central brain.

Aging Cell 2019 02 13;18(1):e12854. Epub 2018 Dec 13.

Division of Human Reproduction and Developmental Genetics, The Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

By the end of neurogenesis in Drosophila pupal brain neuroblasts (NBs), nuclear Prospero (Pros) triggers cell cycle exit and terminates NB lifespan. Here, we reveal that in larval brain NBs, an intrinsic mechanism facilitates import and export of Pros across the nuclear envelope via a Ran-mediated nucleocytoplasmic transport system. In rangap mutants, the export of Pros from the nucleus to cytoplasm is impaired and the nucleocytoplasmic transport of Pros becomes one-way traffic, causing an early accumulation of Pros in the nuclei of the larval central brain NBs. This nuclear Pros retention initiates NB cell cycle exit and leads to a premature decrease of total NB numbers. Our data indicate that RanGAP plays a crucial role in this intrinsic mechanism that controls NB lifespan during neurogenesis. Our study may provide insights into understanding the lifespan of neural stem cells during neurogenesis in other organisms.
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http://dx.doi.org/10.1111/acel.12854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351831PMC
February 2019

Tpeak-Tend/QT interval predicts ST-segment resolution and major adverse cardiac events in acute ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention.

Medicine (Baltimore) 2018 Oct;97(43):e12943

Department of Cardiology, People's Hospital of Zhengzhou University (Henan Provincial People's Hospital), Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan Province, China.

Elevated ST-segment and increased Tpeak-Tend interval (Tp-e) were prognostic predictors in major adverse cardiac events (MACEs) in ST-segment elevation myocardial infarction (STEMI). The electrophysiologic relationship between them during percutaneous coronary intervention (PCI) needs to elucidate.Patients with STEMI admitted to hospital were prospectively evaluated. ST-segment resolution (STR) (defined as ≥50% reduction as the complete-STR [CSTR] group, <50% as incomplete-STR [ISTR] group), Tp-e interval, and ratio of Tp-e to QT interval (Tp-e/QT) were measured, calculated and analyzed with MACEs.Tp-ec interval (corrected Tp-e interval, P < .001) and Tp-e/QT ratio (P < .001) were significantly increased by myocardial infarction and partly recovered post-PCI. Patients with ISTR showed more increased Tp-ec interval (P < .001) and Tp-e/QT ratio (P < .001) than those in CSTR groups post-PCI. In multivariate analysis and receiver operating characteristic curves analysis, Tp-e/QT was an independent and strongest predictor for STR. STR and electrocardiogram parameters with a cutoff value for predicting STR showed prognostic value for MACE in STEMI in Kaplan-Meier survival analysis.Both STR and change of Tp-e parameters were not only predictors of arrhythmia, but also prognostic factors of MACE in patients with STEMI after PCI.
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http://dx.doi.org/10.1097/MD.0000000000012943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221564PMC
October 2018

A positive role of Sin3A in regulating Notch signaling during Drosophila wing development.

Cell Signal 2019 01 12;53:184-189. Epub 2018 Oct 12.

Division of Human Reproduction and Developmental Genetics, The Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Institute of Genetics, Department of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. Electronic address:

Notch is a transmembrane receptor that mediates intercellular signaling through a conserved signaling cascade in all animal species. Transcriptional and posttranscriptional regulation of Notch receptor are important for maintaining Notch signaling activity. Here, we show that depletion of Drosophila Sin3A leads to loss of the adult wing margin and downregulation of Notch target gene expression in the developing wing disc. Sin3A regulates the Notch pathway downstream of Delta and upstream of Notch activation. The role of Sin3A in the Notch pathway is partly mediated by its ability to modulate Notch receptor transcription. Furthermore, the transcriptional activation of Notch receptor is autoregulated by Notch itself. We also provide evidence that Sin3A is required for Notch activation mediated Notch transcription. Together, our data demonstrate that Sin3A activates Notch signaling by promoting Notch transcription and reveal a previously unknown autoregulatory mechanism for Notch signaling activation during Drosophila wing development.
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http://dx.doi.org/10.1016/j.cellsig.2018.10.008DOI Listing
January 2019

Prominin-like, a homolog of mammalian CD133, suppresses di lp6 and TOR signaling to maintain body size and weight in Drosophila.

FASEB J 2019 02 11;33(2):2646-2658. Epub 2018 Oct 11.

Division of Human Reproduction and Developmental Genetics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

CD133 (AC133/prominin-1) has been identified as a stem cell marker and a putative cancer stem cell marker in many solid tumors. Its biologic function and molecular mechanisms remain largely elusive. Here, we show that a fly mutant for prominin-like, a homolog of mammalian CD133, shows a larger body size and excess weight accompanied with higher fat deposits as compared with the wild type. The expression levels of prominin-like are mediated by ecdysone signaling where its protein levels increase dramatically in the fat body during metamorphosis. Prominin-like mutants exhibit higher Drosophila insulin-like peptide 6 (di lp6) levels during nonfeeding stages and increased Akt/ Drosophila target of rapamycin (dTOR) signaling. On an amino acid-restricted diet, prominin-like mutants exhibit a significantly larger body size than the wild type does, similar to that which occurs upon the activation of the dTOR pathway in the fat body. Our data suggest that prominin-like functions by suppressing TOR and dilp6 signaling to control body size and weight. The identification of the physiologic function of prominin-like in Drosophila may provide valuable insight into the understanding of the metabolic function of CD133 in mammals.-Zheng, H., Zhang, Y., Chen, Y., Guo, P., Wang, X., Yuan, X., Ge, W., Yang, R., Yan, Q., Yang, X., Xi, Y. Prominin-like, a homolog of mammalian CD133, suppresses di lp6 and TOR signaling to maintain body size and weight in Drosophila.
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http://dx.doi.org/10.1096/fj.201800123RDOI Listing
February 2019

The histone deacetylase HDAC1 positively regulates Notch signaling during wing development.

Biol Open 2018 Feb 20;7(2). Epub 2018 Feb 20.

Division of Human Reproduction and Developmental Genetics, The Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China

The Notch signaling pathway is highly conserved across different animal species and plays crucial roles in development and physiology. Regulation of Notch signaling occurs at multiple levels in different tissues and cell types. Here, we show that the histone deacetylase HDAC1 acts as a positive regulator of Notch signaling during wing development. Depletion of causes wing notches on the margin of adult wing. Consistently, the expression of Notch target genes is reduced in the absence of HDAC1 during wing margin formation. We further provide evidence that HDAC1 acts upstream of Notch activation. Mechanistically, we show that HDAC1 regulates Notch protein levels by promoting Notch transcription. Consistent with this, the HDAC1-associated transcriptional co-repressor Atrophin (Atro) is also required for transcriptional activation of Notch in the wing disc. In summary, our results demonstrate that HDAC1 positively regulates Notch signaling and reveal a previously unidentified function of HDAC1 in Notch signaling.
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http://dx.doi.org/10.1242/bio.029637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861358PMC
February 2018

Real-time observation of perturbation of a Drosophila embryo's early cleavage cycles with microfluidics.

Anal Chim Acta 2017 Aug 13;982:131-137. Epub 2017 Jun 13.

Institute of Microanalytical Systems, Department of Chemistry, Zhejiang University, Hangzhou 310058, China. Electronic address:

It is of great importance to understand biochemical system's behavior toward environmental perturbation during the development of living organisms. Here a microfluidic platform for Drosophila embryo's online development and observation is presented. The system is capable of developing the embryo's anterior and posterior halves controlled at different temperature environments, and it can be easily coupled with a confocal microscope for real-time image acquisition. The microfluidic chip is consisted of a polymethylmethacrylate (PMMA) substrate with a thickness of 4.0 mm and a polydimethylsiloxane (PDMS) cover designed with a typical 'Y' channel with a depth of 400 μm, width of 800 μm. Temperature gradients were created across the anterior half and posterior half of the embryo by utilizing two streams of laminar flow with different temperatures. It was found that thermal gradient would result in asynchronous development of the two halves of the embryos, and the developing difference was related to the direction of thermal gradient. This may result from the presence of an unknown mechanism located in the anterior half of the embryo, which oversees nuclear division synchronicity. These observations would help better understand compensatory mechanisms of Drosophila embryo's development under environmental perturbations.
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http://dx.doi.org/10.1016/j.aca.2017.05.024DOI Listing
August 2017

Inscuteable maintains type I neuroblast lineage identity via Numb/Notch signaling in the Drosophila larval brain.

J Genet Genomics 2017 03 6;44(3):151-162. Epub 2017 Mar 6.

Division of Human Reproduction and Developmental Genetics, The Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China; Institute of Genetics, Zhejiang University, Hangzhou 310012, China; Department of Genetics, School of Medicine, Zhejiang University, Hangzhou 310012, China; Joint Institute of Genetics and Genomic Medicine Between Zhejiang University and University of Toronto, Zhejiang University, Hangzhou 310012, China. Electronic address:

In the Drosophila larval brain, type I and type II neuroblasts (NBs) undergo a series of asymmetric divisions which give rise to distinct progeny lineages. The intermediate neural progenitors (INPs) exist only in type II NB lineages. In this study, we reveal a novel function of Inscuteable (Insc) that acts to maintain type I NB lineage identity. In insc type I NB clones of mosaic analyses with a repressible cell marker (MARCM), the formation of extra Deadpan (Dpn) NB-like and GMC-like cells is observed. The lack of Insc leads to the defective localization and segregation of Numb during asymmetric cell division. By the end of cytokinesis, this results in insufficient Numb in ganglion mother cells (GMCs). The formation of extra Deadpan (Dpn) cells in insc clones is prevented by the attenuation of Notch activity. This suggests that Insc functions through the Numb/Notch signaling pathway. We also show that in the absence of Insc in type I NB lineages, the cellular identity of GMCs is altered where they adopt an INP-like cell fate as indicated by the initiation of Dpn expression accompanied by a transient presence of Earmuff (Erm). These INP-like cells have the capacity to divide multiple times. We conclude that Insc is necessary for the maintenance of type I NB lineage identity. Genetic manipulations to eliminate most type I NBs with overproliferating type II NBs in the larval brain lead to altered circadian rhythms and defective phototaxis in adult flies. This indicates that the homeogenesis of NB lineages is important for the adult's brain function.
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http://dx.doi.org/10.1016/j.jgg.2017.02.005DOI Listing
March 2017

Premature remodeling of fat body and fat mobilization triggered by platelet-derived growth factor/VEGF receptor in .

FASEB J 2017 05 26;31(5):1964-1975. Epub 2017 Jan 26.

Division of Human Reproduction and Developmental Genetics, The Women's Hospital, and

In fat-body remodeling accompanied with fat mobilization is an ecdysone-induced dynamic process that only occurs during metamorphosis. Here, we show that the activated platelet-derived growth factor/VEGF receptor (PVR) is sufficient to induce shape changes in the fat body, from thin layers of tightly conjugated polygonal cells to clusters of disaggregated round-shaped cells. These morphologic changes are reminiscent of those seen during early pupation upon initiation of fat-body remodeling. Activation of PVR also triggers an early onset of lipolysis and mobilization of internal storage, as revealed by the appearance of small lipid droplets and up-regulated lipolysis-related genes. We found that PVR displays a dynamic expression pattern in the fat body and peaks at the larval-prepupal transition under the control of ecdysone signaling. Removal of PVR, although it does not prevent ecdysone-induced fat-body remodeling, causes ecdysone signaling to be up-regulated. Our data reveal that PVR is active in a dual-secured mechanism that involves an ecdysone-induced fat-body remodeling pathway and a reinforced PVR pathway for effective lipid mobilization. Ectopic expression of activated c-kit-the mouse homolog of PVR in the fat body-also results in a similar phenotype. This may suggest a novel function of c-kit as it relates to lipid metabolism in mammals.-Zheng, H., Wang, X., Guo, P., Ge, W., Yan, Q., Gao, W., Xi, Y., Yang, X. Premature remodeling of fat body and fat mobilization triggered by platelet-derived growth factor/VEGF receptor in .
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http://dx.doi.org/10.1096/fj.201601127RDOI Listing
May 2017

Effects of electronically stimulating Tianshu (ST 25) and Dachangshu (BL 25), Quchi (LI 11) and Shangjuxu (ST 37) on the expressions of jejunum c-kit protein and c-kit mRNA in rats with functional diarrhea.

J Tradit Chin Med 2016 12;36(6):779-83

Objective: To investigate the effects of electronically stimulating Tianshu (ST 25) and Dachangshu (BL 25), Quchi (LI 11) and Shangjuxu (ST 37) on the jejunum c-kit protein and c-kit mRNA in rats with functional diarrhea (FD).

Methods: FD models were established through intragastric administration with folium sennae. Experimental rats were then divided into 4 groups: blank group, model group, electroacupuncture group Ⅰ [Tianshu (ST 25) and Dachangshu (BL 25) of both sides] and electroacupuncture group Ⅱ [Quchi (Li 11) and Shangjuxu (ST 37) of both sides], 10 in each. After treatment with electroacupuncture for 10 days, The expressions of jejunum c-kit protein and c-kit mRNA in each group were detected with Western blot and Real-Time quantitative real-time polymerase chain reaction (PCR).

Results: The expressions of c-kit protein and c-kit mRNA in the model group increased significantly compared to those in the blank group (P < 0.01); the expressions in electroacupuncture group Ⅰsignificantly decreased compared to those in the model group (P < 0.01).

Conclusion: Our findings suggest that electronicall stimulating both Tianshu (ST 25) and Dachangshu (BL 25) significantly increased the expressions of jejunum c-kit protein and c-kit mRNA in FD rats, which means the treatment might have better therapeutic effects on FD.
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http://dx.doi.org/10.1016/s0254-6272(17)30014-6DOI Listing
December 2016

Fat body remodeling and homeostasis control in Drosophila.

Life Sci 2016 Dec 20;167:22-31. Epub 2016 Oct 20.

Division of Human Reproduction and Developmental Genetics, the Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Institute of Genetics, Zhejiang University and Department of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. Electronic address:

Remarkable advances have been made in recent years in our understanding of the Drosophila fat body and its functions in energy storage, immune response and nutrient sensing. The fat body interplays with other tissues to respond to the physiological needs of the body's growth and coordinates various metabolic processes at different developmental stages and under different environmental conditions. The identification of various conserved genetic functions and signaling pathways relating to the Drosophila fat body may provide clues to lipometabolic disease and other aspects of tissue remodeling in humans. Here, we discuss recent insights into how regulation of fat body remodeling contributes to hemostasis with a special focus on how signaling networks and internal physiological states shape different aspects of the lipid metabolism in Drosophila.
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http://dx.doi.org/10.1016/j.lfs.2016.10.019DOI Listing
December 2016

Stox1 as a novel transcriptional suppressor of Math1 during cerebellar granule neurogenesis and medulloblastoma formation.

Cell Death Differ 2016 12 26;23(12):2042-2053. Epub 2016 Aug 26.

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

Cerebellar granule neuronal progenitors (GNPs) are the precursors of cerebellar granule cells (CGCs) and are believed to be the cell of origin for medulloblastoma (MB), yet the molecular mechanisms governing GNP neurogenesis are poorly elucidated. Here, we demonstrate that storkhead box 1 (Stox1), a forkhead transcriptional factor, has a pivotal role in cerebellar granule neurogenesis and MB suppression. Expression of Stox1 is upregulated along with GNP differentiation and repressed by activation of sonic hedgehog (SHH) signaling. Stox1 exerts its neurogenic and oncosuppressing effect via direct transcriptional repression of Math1, a basic helix-loop-helix transcription activator essential for CGC genesis. This study illustrates a SHH-Stox1-Math1 regulatory axis in normal cerebellar development and MB formation.
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http://dx.doi.org/10.1038/cdd.2016.85DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136492PMC
December 2016
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