AIM： To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS： In a mouse model of gastric bleeding with high dose of indo...AIM： To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS： In a mouse model of gastric bleeding with high dose of indomethacin （20 mg/kg）, an EP4-selective agonist was administered orally. Stomach lesions and gastric mucous regeneration were monitored. In a mouse model of chronic gastric ulcer induced by acetic acid, EP4 agonist effect on the healing of chronic gastric ulcer was evaluated in the presence or absence of low dose indomethadn （3 mg/kg）. In cultured human gastric mucous cells, EP4 agonist effect on indomethacin- induced apoptosis was assessed by flow cytometry. RESULTS： The EP4-selective agonist reduced high dose indomethacin-induced acute hemorrhagic damage and promoted mucous epithelial regeneration. Low-dose indomethacin aggravated ulcer bleeding and inflammation, and delayed the healing of the established chronic gastric ulcer. The EP4 agonist, when applied locally, not only offset indomethacin-induced gastric bleeding and inflammation, but also accelerated ulcer healing. In the absence of indomethacin, the EP4 agonist even accelerated chronic gastric ulcer healing and suppressed inflammatory cell infiltration in the granulation tissue. In vitro, the EP4 agonist protected human gastric mucous cells from indomethacin-induced apoptosis.CONCLUSION： EP4-selective agonist may prevent indomethacin-induced gastric lesions and promote healing of existing and i ulcers, via promoting mucous epithelial cells. proliferation and survival of mucous epithelial cells.展开更多
Objective: The results of a previous study showed that a clear dysregulation was evident in the global gene expression of the BCL11A-suppressed B-lymphoma cells. In this study, the bone morphogenetic protein receptor,...Objective: The results of a previous study showed that a clear dysregulation was evident in the global gene expression of the BCL11A-suppressed B-lymphoma cells. In this study, the bone morphogenetic protein receptor, type II(BMPR2), E1 A binding protein p300(EP300), transforming growth factor-β2(TGFβ2), and tumor necrosis factor, and alpha-induced protein 3(TNFAIP3) gene expression patterns in B-cell malignancies were studied. Methods: The relative expression levels of BMPR2, EP300, TGFβ2, and TNFAIP3 mRNA in B-lymphoma cell lines, myeloid cell lines, as well as in cells from healthy volunteers, were determined by real-time quantitative reverse transcriptpolymerase chain reaction(qRT-PCR) with SYBR Green Dye. Glyceraldehyde-3-phosphate dehydrogenase(GAPDH) was used as reference. Results: The expression level of TGFβ2 mRNA in B-lymphoma cell lines was significantly higher than those in the cells from the healthy control(P<0.05). However, the expression level of TNFAIP3 mRNA in B-malignant cells was significantly lower than that of the healthy control(P<0.05). The expression levels of BMPR2 and EP300 mRNA showed no significant difference between B-malignant cell lines and the healthy group(P>0.05). In B-lymphoma cell lines, correlation analyses revealed that the expression of BMPR2 and TNFAIP3(r=0.882, P=0.04) had significant positive relation. The expression levels of BMPR2, EP300, and TNFAIP3 mRNA in cell lines from myeloid leukemia were significantly lower than those in the cells from the healthy control(P<0.05). The expression levels of TGFβ2 mRNA showed no significant difference between myeloid leukemia cell lines and the healthy control or B-malignant cell lines(P>0.05). The expression levels of BMPR2, EP300, and TNFAIP3 mRNA in B-lymphoma cells were significantly higher than those of the myeloid leukemia cells(P<0.05).Conclusion: Different expression patterns of BMPR2, EP300, TGFβ2, and TNFAIP3 genes in B-lymphoma cells exist.展开更多
背景与目的:三阴乳腺癌(triple-negative breast cancer)指雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)和HER2/neu均无表达的乳腺癌,被认为是一种独立的临床病理类型,以侵袭性强、预后较差为主要特征的乳...背景与目的:三阴乳腺癌(triple-negative breast cancer)指雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)和HER2/neu均无表达的乳腺癌,被认为是一种独立的临床病理类型,以侵袭性强、预后较差为主要特征的乳腺癌。本研究目的在于分析三阴乳腺癌的临床特征和影响预后的因素。方法:收集2000年1月至2004年12月中山大学肿瘤防治中心收治的经病理组织学证实、有完整随访资料的1280例可手术乳腺癌患者的临床资料,经病理学检查证实ER、PR和HER2/neu均为阴性的三阴乳腺癌305例(23.8%)。回顾性分析三阴乳腺癌患者的临床特征、复发及生存情况。结果:本组乳腺癌患者中有23.8%(305/1280)是三阴乳腺癌,多见于年轻患者,诊断时肿块较大、局部淋巴结阳性者较多,有乳腺癌家族史的患者较多。截止至2007年6月,三阴乳腺癌组患者中位随访时间为52个月(28～89个月),有234例患者出现复发及转移,94例已死亡。三阴乳腺癌组局部复发率与非三阴乳腺癌患者相比无显著性差异;但三阴乳腺癌患者远处转移发生率显著增高,主要表现肺转移(HR=4.41,P<0.001)和肝转移(HR=2.13,P=0.006)发生率高。生存分析显示,三阴乳腺癌患者的5年无病生存率和总生存率分别为73.7%和88.5%,均显著低于非三阴乳腺癌患者(80.8%和92.8%,P=0.025,P=0.010)。多因素分析显示,肿块大小和淋巴结状况是影响三阴乳腺癌预后的两个主要因素。结论:三阴乳腺癌在乳腺癌中占有约1/4的比例。这些患者往往年轻、有乳腺癌家族史、肿块较大、淋巴结阳性多。三阴乳腺癌容易出现肺转移和肝转移,这可能是导致三阴乳腺癌预后较差的重要原因。展开更多
Fever is an adaptive host response coordinated by the central nervous system （CNS） during systemic immune challenge. Recent research shed light on the mechanism of fever generation, particularly the underlying neura...Fever is an adaptive host response coordinated by the central nervous system （CNS） during systemic immune challenge. Recent research shed light on the mechanism of fever generation, particularly the underlying neural pathways. In this review, we first briefly summarize current views on the mechanism of sensing microbial infection by the nervous system, and the roles of prostaglandin E2 （PGE2） and its receptors in fever; then we focus on the neural circuits underlying fever generation, particularly their relationship with the distribution of PGE2 receptors within the CNS. At the end, an overall neurochemical model of fever generation is presented, pointing to the direction for future studies.展开更多
Objective To determine the expression of E-prostanoid1 (EP 1) and F-prostanoid (FP) receptor mRNAs in iris-ciliary bodies of the human eye using in situ hybridization.Methods EP 1 and FP receptor mRNAs were detect...Objective To determine the expression of E-prostanoid1 (EP 1) and F-prostanoid (FP) receptor mRNAs in iris-ciliary bodies of the human eye using in situ hybridization.Methods EP 1 and FP receptor mRNAs were detected by riboprobes labeled with digoxigenin on paraffin sections of the iris-ciliary body tissue of the human eye using in situ hybridization. Results EP 1 and FP receptor mRNAs were highly expressed in blood vessels, muscles and the endothelia of the iris. EP 1 receptor hybridization signals were present in all muscle fibers of the ciliary body. Hybridization signal corresponding to FP receptor mRNA transcript was predominantly expressed in the circular muscle and in the collagenous connective tissues of the ciliary body. FP receptor mRNA was not detected in radial and longitudinal muscles. Conclusions EP 1 and FP receptor mRNAs in human ocular tissues appear to be widely localized in the functional sites of the respective receptor agonists. Selective localization of EP 1 and FP receptor mRNAs in the circular muscles and collagenous connective tissues of the ciliary body suggests that EP 1 and FP receptors play an important role in enhancing uveoscleral outflow of aqueous humor.展开更多
Objective The glial cells of the central nervous system are involved in tripartite signaling,therefore we have been investigating the relationship between sensory neurons and non-neuronal cells in isolated preparation...Objective The glial cells of the central nervous system are involved in tripartite signaling,therefore we have been investigating the relationship between sensory neurons and non-neuronal cells in isolated preparations of dorsal root ganglia(DRG).Methods The mixed cell cultures of dissociated DRG cells were separated to yield enriched fractions of IB4-positive cells(small diameter,non-peptidergic cells),IB4-negative cells(small diameter,peptidergic cells,and large diameter cells),and non-neuronal cells(principally satellite glial cells,Schwann cells and fibroblasts).Adenylyl cyclase activity was assayed by measuring production of [3H]cAMP from cells preloaded with [3H]adenine.Results PGE2 and the PGI2 mimetic cicaprost stimulated adenylyl cyclase activity which was inhibited by ONO-AE3-208(EP4 antagonist)or CAY10441(IP antagonist)with estimated pA2 values of 8.9 and 8.2,respectively.Surprisingly,both PGE2 and cicaprost-stimulated [3H] cAMP production was greatest in the non-neuronal cell preparation.Furthermore,when the number of non-neuronal cells was kept constant and the number of neuronal cells was increased,we observed a progressive decrease in prostanoid-stimulated activity.Conclusions Sensory neurons appear to regulate prostanoid receptor-mediated cell signaling in non-neuronal cells within the DRG.展开更多
文摘AIM： To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS： In a mouse model of gastric bleeding with high dose of indomethacin （20 mg/kg）, an EP4-selective agonist was administered orally. Stomach lesions and gastric mucous regeneration were monitored. In a mouse model of chronic gastric ulcer induced by acetic acid, EP4 agonist effect on the healing of chronic gastric ulcer was evaluated in the presence or absence of low dose indomethadn （3 mg/kg）. In cultured human gastric mucous cells, EP4 agonist effect on indomethacin- induced apoptosis was assessed by flow cytometry. RESULTS： The EP4-selective agonist reduced high dose indomethacin-induced acute hemorrhagic damage and promoted mucous epithelial regeneration. Low-dose indomethacin aggravated ulcer bleeding and inflammation, and delayed the healing of the established chronic gastric ulcer. The EP4 agonist, when applied locally, not only offset indomethacin-induced gastric bleeding and inflammation, but also accelerated ulcer healing. In the absence of indomethacin, the EP4 agonist even accelerated chronic gastric ulcer healing and suppressed inflammatory cell infiltration in the granulation tissue. In vitro, the EP4 agonist protected human gastric mucous cells from indomethacin-induced apoptosis.CONCLUSION： EP4-selective agonist may prevent indomethacin-induced gastric lesions and promote healing of existing and i ulcers, via promoting mucous epithelial cells. proliferation and survival of mucous epithelial cells.
基金supported by the Guangdong Province Key Foundation of Science and Technology Program (Grant No.2009B0507000029)the Guangdong Province Science and Technology Program (Grant No.2012B031800474)a grant from the Overseas Chinese Affairs Office of the State Council Key Discipline Construction Fund (Grant No.51205002)
文摘Objective: The results of a previous study showed that a clear dysregulation was evident in the global gene expression of the BCL11A-suppressed B-lymphoma cells. In this study, the bone morphogenetic protein receptor, type II(BMPR2), E1 A binding protein p300(EP300), transforming growth factor-β2(TGFβ2), and tumor necrosis factor, and alpha-induced protein 3(TNFAIP3) gene expression patterns in B-cell malignancies were studied. Methods: The relative expression levels of BMPR2, EP300, TGFβ2, and TNFAIP3 mRNA in B-lymphoma cell lines, myeloid cell lines, as well as in cells from healthy volunteers, were determined by real-time quantitative reverse transcriptpolymerase chain reaction(qRT-PCR) with SYBR Green Dye. Glyceraldehyde-3-phosphate dehydrogenase(GAPDH) was used as reference. Results: The expression level of TGFβ2 mRNA in B-lymphoma cell lines was significantly higher than those in the cells from the healthy control(P<0.05). However, the expression level of TNFAIP3 mRNA in B-malignant cells was significantly lower than that of the healthy control(P<0.05). The expression levels of BMPR2 and EP300 mRNA showed no significant difference between B-malignant cell lines and the healthy group(P>0.05). In B-lymphoma cell lines, correlation analyses revealed that the expression of BMPR2 and TNFAIP3(r=0.882, P=0.04) had significant positive relation. The expression levels of BMPR2, EP300, and TNFAIP3 mRNA in cell lines from myeloid leukemia were significantly lower than those in the cells from the healthy control(P<0.05). The expression levels of TGFβ2 mRNA showed no significant difference between myeloid leukemia cell lines and the healthy control or B-malignant cell lines(P>0.05). The expression levels of BMPR2, EP300, and TNFAIP3 mRNA in B-lymphoma cells were significantly higher than those of the myeloid leukemia cells(P<0.05).Conclusion: Different expression patterns of BMPR2, EP300, TGFβ2, and TNFAIP3 genes in B-lymphoma cells exist.
文摘背景与目的:三阴乳腺癌(triple-negative breast cancer)指雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)和HER2/neu均无表达的乳腺癌,被认为是一种独立的临床病理类型,以侵袭性强、预后较差为主要特征的乳腺癌。本研究目的在于分析三阴乳腺癌的临床特征和影响预后的因素。方法:收集2000年1月至2004年12月中山大学肿瘤防治中心收治的经病理组织学证实、有完整随访资料的1280例可手术乳腺癌患者的临床资料,经病理学检查证实ER、PR和HER2/neu均为阴性的三阴乳腺癌305例(23.8%)。回顾性分析三阴乳腺癌患者的临床特征、复发及生存情况。结果:本组乳腺癌患者中有23.8%(305/1280)是三阴乳腺癌,多见于年轻患者,诊断时肿块较大、局部淋巴结阳性者较多,有乳腺癌家族史的患者较多。截止至2007年6月,三阴乳腺癌组患者中位随访时间为52个月(28～89个月),有234例患者出现复发及转移,94例已死亡。三阴乳腺癌组局部复发率与非三阴乳腺癌患者相比无显著性差异;但三阴乳腺癌患者远处转移发生率显著增高,主要表现肺转移(HR=4.41,P<0.001)和肝转移(HR=2.13,P=0.006)发生率高。生存分析显示,三阴乳腺癌患者的5年无病生存率和总生存率分别为73.7%和88.5%,均显著低于非三阴乳腺癌患者(80.8%和92.8%,P=0.025,P=0.010)。多因素分析显示,肿块大小和淋巴结状况是影响三阴乳腺癌预后的两个主要因素。结论:三阴乳腺癌在乳腺癌中占有约1/4的比例。这些患者往往年轻、有乳腺癌家族史、肿块较大、淋巴结阳性多。三阴乳腺癌容易出现肺转移和肝转移,这可能是导致三阴乳腺癌预后较差的重要原因。
文摘Fever is an adaptive host response coordinated by the central nervous system （CNS） during systemic immune challenge. Recent research shed light on the mechanism of fever generation, particularly the underlying neural pathways. In this review, we first briefly summarize current views on the mechanism of sensing microbial infection by the nervous system, and the roles of prostaglandin E2 （PGE2） and its receptors in fever; then we focus on the neural circuits underlying fever generation, particularly their relationship with the distribution of PGE2 receptors within the CNS. At the end, an overall neurochemical model of fever generation is presented, pointing to the direction for future studies.
文摘Objective To determine the expression of E-prostanoid1 (EP 1) and F-prostanoid (FP) receptor mRNAs in iris-ciliary bodies of the human eye using in situ hybridization.Methods EP 1 and FP receptor mRNAs were detected by riboprobes labeled with digoxigenin on paraffin sections of the iris-ciliary body tissue of the human eye using in situ hybridization. Results EP 1 and FP receptor mRNAs were highly expressed in blood vessels, muscles and the endothelia of the iris. EP 1 receptor hybridization signals were present in all muscle fibers of the ciliary body. Hybridization signal corresponding to FP receptor mRNA transcript was predominantly expressed in the circular muscle and in the collagenous connective tissues of the ciliary body. FP receptor mRNA was not detected in radial and longitudinal muscles. Conclusions EP 1 and FP receptor mRNAs in human ocular tissues appear to be widely localized in the functional sites of the respective receptor agonists. Selective localization of EP 1 and FP receptor mRNAs in the circular muscles and collagenous connective tissues of the ciliary body suggests that EP 1 and FP receptors play an important role in enhancing uveoscleral outflow of aqueous humor.
文摘Objective The glial cells of the central nervous system are involved in tripartite signaling,therefore we have been investigating the relationship between sensory neurons and non-neuronal cells in isolated preparations of dorsal root ganglia(DRG).Methods The mixed cell cultures of dissociated DRG cells were separated to yield enriched fractions of IB4-positive cells(small diameter,non-peptidergic cells),IB4-negative cells(small diameter,peptidergic cells,and large diameter cells),and non-neuronal cells(principally satellite glial cells,Schwann cells and fibroblasts).Adenylyl cyclase activity was assayed by measuring production of [3H]cAMP from cells preloaded with [3H]adenine.Results PGE2 and the PGI2 mimetic cicaprost stimulated adenylyl cyclase activity which was inhibited by ONO-AE3-208(EP4 antagonist)or CAY10441(IP antagonist)with estimated pA2 values of 8.9 and 8.2,respectively.Surprisingly,both PGE2 and cicaprost-stimulated [3H] cAMP production was greatest in the non-neuronal cell preparation.Furthermore,when the number of non-neuronal cells was kept constant and the number of neuronal cells was increased,we observed a progressive decrease in prostanoid-stimulated activity.Conclusions Sensory neurons appear to regulate prostanoid receptor-mediated cell signaling in non-neuronal cells within the DRG.
