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Featured researches published by Yongyi Fan.


The Journal of Physiology | 2004

Ghrelin stimulates neurogenesis in the dorsal motor nucleus of the vagus

Weizhen Zhang; Theodore R. Lin; Yuexuan Hu; Yongyi Fan; Lili Zhao; Edward L. Stuenkel; Michael W. Mulholland

Ghrelin, a gastric peptide hormone, has been reported to regulate growth hormone secretion and energy homeostasis. Here we show that ghrelin promotes neural proliferation in vivo and in vitro in the rat dorsal motor nucleus of the vagus (DMNV). Ghrelin receptor mRNA and immunoreactivity were detected in tissues from DMNV. Systemic administration of ghrelin (130 nmol kg−1) significantly increased 5‐bromo‐2′‐deoxyuridine (BrdU) incorporation in the DMNV in adult rats with cervical vagotomy (BrdU positive cells; from 27 ± 4 to 69 ± 14 n= 5, P < 0.05). In vitro, exposure of cultured DMNV neurones to ghrelin significantly increased the percentage of BrdU incorporation into cells in both dose‐dependent (10−9–10−6m), and time‐dependent (6 h to 48 h) manners. Ghrelin significantly increased voltage‐activated calcium currents in isolated single DMNV neurones from a mean maximal change of 141 ± 26 pA to 227 ± 37 pA. Upon removal of ghrelin, calcium currents slowly returned to baseline. Blocking L‐type calcium channels by diltiazem (10 μm) significantly attenuated ghrelin‐mediated increments in BrdU incorporation (n= 5, P < 0.05). Ghrelin acts directly on DMNV neurones to stimulate neurogenesis.


Annals of Surgery | 2002

Interferon-gamma expression by intraepithelial lymphocytes results in a loss of epithelial barrier function in a mouse model of total parenteral nutrition

Hua Yang; İrfan Kırıştıoğlu; Yongyi Fan; Benjamin Forbush; D. Keith Bishop; Paul A. Antony; Hong Zhou; Daniel H. Teitelbaum

ObjectiveTo determine the etiology of the loss of epithelial barrier function observed with the administration of total parenteral nutrition (TPN) in a mouse model. Summary Background DataRemoval of enteral nutrition with the administration of TPN is associated with a loss of intestinal epithelial barrier function. The etiology of this barrier loss is not clear. Because intraepithelial lymphocytes (IELs) produce a number of cytokines that may alter epithelial permeability, the authors investigated IEL cytokine expression in a mouse model of TPN. MethodsAdult C57BL/6 mice received TPN or enteral diet for 7 days. IELs were subsequently harvested and the mRNA expression of cytokines was measured. Epithelial barrier function was assessed in vitro with 51Cr-EDTA in Ussing chambers and was expressed as the permeability coefficient (Papp). ResultsIEL mRNA expression of interferon-gamma (IFN-&ggr;) rose from 0.14 ± 0.07 in the control (enterally fed) group to 0.44 ± 0.11 attomoles/&mgr;L in the TPN group (P < .05). Transforming growth factor-&bgr;1 declined slightly but not significantly, from 0.75 ± 0.35 to 0.55 ± 0.18 attomoles/&mgr;L in the control and TPN groups, respectively. Epithelial barrier function declined significantly with TPN compared to controls. To assess the relevance of IFN-&ggr; changes, permeability in IFN-&ggr; knockout mice was studied. Barrier function was significantly higher in IFN-&ggr; knockout mice on TPN compared to C57BL/6 mice that received TPN. ConclusionsIEL cytokine expression changes significantly with TPN administration. The partial correction with IFN-&ggr; knockout mice suggests that an upregulation of IFN-&ggr; expression is one mechanism responsible for the loss of the epithelial barrier associated with TPN.


Digestive Diseases and Sciences | 2002

Total Parenteral Nutrition-Associated Changes in Mouse Intestinal Intraepithelial Lymphocytes

İrfan Kırıştıoğlu; Paul A. Antony; Yongyi Fan; Benjamin Forbush; R. Lee Mosley; Hua Yang; Daniel H. Teitelbaum

Intraepithelial lymphocytes (IEL) play a major role in mucosal defense mechanisms against intraluminal foreign antigens. To address the role luminal nutrients have on the phenotype and function of the IEL, we administered total parenteral nutrition (TPN) to mice, with the absence of enteral intake. We hypothesized that administration of TPN would result in changes in the phenotype and function of the IEL. For this, we utilized a mouse model of TPN. A significant decline in the CD4+ IEL population occurred with TPN. Additionally, the CD8+,CD44+ IEL subset showed a 65% decline (P < 0.05), and the CD4+,CD44+ subset declined by 55% with TPN (P < 0.05). The CD8αβ+ population (a marker of thymic-dependence) also declined by 92% (P < 0.01) with TPN. IEL in the TPN group showed a significantly lower degree of in vitro proliferation. In conclusion, the IEL showed significant phenotypic changes with TPN including the loss of the thymic-derived population. Functionally, the IEL showed a significant decline in proliferation. Such changes demonstrate the important role luminal nutrients have on IEL phenotype and function.


Journal of Surgical Research | 2003

Alteration of intestinal intraepithelial lymphocytes after massive small bowel resection.

Hua Yang; Yongyi Fan; Robert Finaly; Daniel H. Teitelbaum

BACKGROUND Intraepithelial lymphocytes (IEL) comprise the inner most layer of the gut immune system, and play a critical role in protecting the host from enteric organisms. Massive small bowel resection (MSBR) is one such clinical condition where patients are at particularly high risk for the development of such enteric infectious complications. Because of this, we hypothesized that the IEL may change significantly after the formation of a MSBR. To address this, a mouse model of MSBR was created and the acute phenotypic and functional characteristics of the IEL were studied. MATERIALS AND METHODS Mice underwent a 70% mid-small bowel resection. After 7 days, IEL were isolated and analyzed for phenotypic changes by flow cytometry. IEL cytokine expression was performed with semiquantitative polymerase chain reaction techniques. To assess the functional significance of these changes, IEL proliferative response was assessed in vitro.Results. MSBR led to significant decreases in specific IEL subpopulations: CD 44+ (used as a marker of cell maturity); CD 8alphabeta+ (marker of thymic derivation), and CD 69+ (marker of T cell activation). Compared with controls, IEL TNF-alpha mRNA expression increased 84%, while IL-2 and IL-10 mRNA expression decreased by 69 and 72%, respectively. Spontaneous proliferation of IEL in the MSBR group was significantly higher than controls, however, proliferation failed to increase with T cell stimulation.Conclusion. These changes suggest a shift to a more immature and possibly less activated cell population. It is possible that such alterations may play an important role in the increase in enterically derived infections in patients with MSBR.


American Journal of Physiology-gastrointestinal and Liver Physiology | 2003

Intraepithelial lymphocyte-derived interferon-γ evokes enterocyte apoptosis with parenteral nutrition in mice

Hua Yang; Yongyi Fan; Daniel H. Teitelbaum


Journal of Surgical Research | 2005

Thrombin and PAR-1-AP Increase Proinflammatory Cytokine Expression in C6 Cells1

Yongyi Fan; Weizhen Zhang; Michael W. Mulholland


Journal of Surgical Research | 2007

Interleukin-1β and Interleukin-6 Stimulate Matrix Metalloproteinase-9 Secretion in Cultured Myenteric Glia

Theodore R. Lin; Weizhen Zhang; Yongyi Fan; Michael W. Mulholland


Gastroenterology | 2000

Altered expression of intraepithelial lymphocyte (IEL) keratinocyte growth factor (KGF) mRNA in the mouse

Paul A. Antony; Hua Yang; Yongyi Fan; Daniel H. Teitelbaum


Gastroenterology | 2000

Villus atrophy in a mouse model of total parenteral nutrition: Apoptosis as a cause and potential mechanisms

Hua Yang; Yongyi Fan; Paul A. Antony; Daniel H. Teitelbaum


Gastroenterology | 2001

Interferon-ψ mediates epithelial cell apoptosis through a Fas/FasL interaction in a mouse model of total parenteral nutrition (TPN)

Hua Yang; Yongyi Fan; Daniel H. Teitelbaum

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Hua Yang

University of Michigan

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