Distribution of lithostathine in the mouse lemur brain with aging and Alzheimer's-like pathology

We analyzed the cellular distribution of the pancreatic inflammatory protein lithostathine and its receptor EXTL3 in the brain of the lemurian primate Microcebus murinus which develops amyloid deposits along with aging. In adult animals (2-4.5 years old), lithostathine and EXTL3 immunoreactivities were largely distributed in the whole brain, and more intensively in almost all cortical layers and hippocampal formation. Lithostathine was observed in the perikarya and neurites of cortical neurons but also in glial cells in the border of the ventricle and the corpus callosum. In healthy aged animals (8-13 years old), highest densities of lithostathine-containing cells were observed, mainly in occipital and parietal cortex. In aged animals with Aβ deposits, the increase in lithostathine immunoreactivity was lower as compared with aged animals. Noteworthy, lithostathine-immunopositive cells did almost never colocalize with Aβ plaques. In conclusion, lithostathine immunoreactivity in adult Microcebus murinus appeared ubiquitous and particularly in visual, sensorial, and cognitive brain areas. Immunoreactivity increased with aging and appeared markedly affected in neuropathological conditions. Its possible neuroprotection or neurodegeneration role in Alzheimer pathology deserves therefore to be investigated.     

HIP/PAP, a member of the reg family, is expressed in glucagon-producing enteropancreatic endocrine cells and tumors

Hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) protein, a member of the reg family, is constitutively expressed by some specialized epithelial cell subsets in the digestive tract and the pancreas. We performed a detailed analysis of the expression of HIP/PAP protein in normal digestive endocrine cells according to their localization, lineage, and differentiation stage, and in digestive endocrine tumors according to their site of origin and hormonal profile. In both adult and fetal normal tissues, HIP/PAP expression was detected only in endocrine cells of the small intestine, ascending colon, and pancreas. Two different expression patterns were identified: (a) a strong cytoplasmic labeling observed in the endocrine cells of the digestive mucosa and the outer rim of Langerhans islets specialized in the synthesis of glucagon and glucagon-like peptides; (b) a weak cytoplasmic immunoreactivity observed in the other pancreatic endocrine cell populations. HIP/PAP expression was detected in 36 of the 184 cases of digestive endocrine tumors examined; 32 of these cases (89%) were pancreatic. The 2 patterns observed in the normal state were retained: (a) a strong labeling was observed in 5% to 100% of tumor cells in 26 tumors, all expressing glucagon or glucagon-like peptides; (b) a weak labeling was present in 10 tumors, presenting various hormonal profiles. In conclusion, a strong expression of HIP/PAP is characteristic of glucagon-producing normal and neoplastic enteropancreatic endocrine cells. Our results lend further support to the concept that members of the reg family play regulatory roles in various endocrine cell populations and that their expression in endocrine cells is lineage-specific.     

血清Reg Ⅳ蛋白在胃癌中的表达

目的 检测Reg Ⅳ蛋白在胃癌患者血清中的表达,探讨其作为浸润性胃癌检测标志物的可能性。 方法 酶联免疫分析法定量检测64例胃癌患者血清中Reg Ⅳ蛋白的表达水平。结果 肿瘤浸润至肌层（T2）和浆膜层（T3）的胃癌患者血清Reg Ⅳ蛋白水平要显著高于肿瘤局限在黏膜层和黏膜下层（T1）者（P=0.009）;有淋巴结转移者血清Reg Ⅳ蛋白水平要高于无淋巴结转移者（P=0.047）; 病理Ⅲ期患者血清Reg Ⅳ蛋白水平高于病理Ⅰ期患者（P=0.024）。结论 Reg Ⅳ蛋白可能与胃癌的生长侵袭有关。     

狭叶红景天中百脉根甙分离方法改进的研究

目的 寻找更有效提取红景天植物中红景天甙和百脉根甙的方法.方法 红景天粗粉用乙醇回流提取,浓缩至小体积,MgO粉拌样去除杂质,用石油醚、氯仿、乙酸乙酯、甲醇分别加热回流再提取,浓缩至小体积的浓缩液上SiO2─MgO混合柱,用乙酸乙酯、甲醇:乙酸乙酯溶剂梯度洗脱.结果 分离得到红景天甙和百脉根甙两种化合物.结论 此提取方法可得到纯的红景天甙和百脉根甙.     

Regenerating gene (REG) product and its potential clinical usage

Introduction: The regenerating gene (Reg) was identified in regenerating islets and its related genes were revealed to constitute the Reg gene family. Reg family proteins act as growth factors for several cells. Recently, autoimmunity against the Reg family proteins has been reported in several diseases. In addition, the Reg family genes were found to be expressed in a large number of cancers and to influence prognosis.

Areas covered: The historical background and current view of the structure, function, and expression of Reg family genes/proteins and their physiological/pathological significance in several diseases are described. Based on the findings, the diagnostic/therapeutic potential of Reg family genes/proteins is also discussed.

Expert opinion: Autoimmunity against Reg family proteins may be a new diagnostic marker and/or therapeutic target for immune-mediated diseases. Treatment aimed at the expansion of the β-cell mass by the Reg genes/proteins, combined with the abrogation of autoimmunity, constitutes a potential approach for the treatment of diabetes. Conversely, some cancer cells have gained the ability to overexpress the Reg genes/proteins, thereby enhancing their proliferative capacities, resulting in these cells having a considerable growth advantage. Thus, the Reg genes/proteins are expected to be a new prognostic marker in cancer and/or a future therapeutic target.     

血清PGⅠ、PGⅡ及RegⅣ水平检测在胃癌患者中的临床意义

目的 研究血清PGⅠ、PGⅡ及RegⅣ水平检测对胃癌患者的临床意义.方法 整群选取该院2012年3—12月收治的216例胃部病变患者,检测所有患者血清中PGⅠ、PGⅡ、RegⅣ以及CEA、CA19-9水平,其中18例胃癌患者,设为胃癌组,198 例胃病患者,设为胃病组. 结果 血清PG 和RegⅣ 联合检测胃癌的敏感性、特异性分别为 83.3%、78.2%,血清CEA联合CA19-9检测胃癌的敏感性、特异性分别为55.6%、59.1%. PG联合RegⅣ检验胃癌的敏感性、特异性都明显比CEA联合CA19-9检验高. 差异有统计学意义. 结论 PG和Reg联合检验具有很高的敏感性和特异性,对胃癌的诊断具有高的辅助诊断价值.     

Pancreatic regenerating protein (reg I) and reg I receptor mRNA are upregulated in rat pancreas after induction of acute pancreatitis

AIM: Pancreatic regenerating protein (reg Ⅰ) stimulates pancreatic regeneration after pancreatectomy and is mitogenic to ductal and β-cells. This suggests that reg Ⅰ and its receptor may play a role in recovery after pancreatic injury. We hypothesized that reg Ⅰ and its receptor are induced in acute pancreatitis.METHODS: Acute pancreatitis was induced in male Wistar rats by retrograde injection of 3% sodium taurocholate into the pancreatic duct. Pancreata and serum were collected 12, 24, and 36 hours after injection and from normal controls (4 rats/group). Reg Ⅰ receptor mRNA, serum reg Ⅰ protein, and tissue reg Ⅰ protein levels were determined by Northern analysis, enzymelinked immunosorbent assay (ELISA), and Western analysis, respectively. Immunohistochemistry was used to localize changes in reg Ⅰ and its receptor.RESULTS: Serum amylase levels and histology confirmed necrotizing pancreatitis in taurocholate treated rats. There was no statistically significant change in serum reg Ⅰ concentrations from controls. However,Western blot demonstrated increased tissue levels of reg Ⅰ at 24 and 36 h. This increase was localized primarily to the acinar cells and the ductal cells by immunohistochemistry. Northern blot demonstrated a significant increase in reg Ⅰ receptor mRNA expression with pancreatitis. Immunohistochemistry localized this increase to the ductal cells, islets, and acinar cells.CONCLUSION: Acute pancreatitis results in increased tissue reg Ⅰ protein levels localized to the acinar and ductal cells, and a parallel threefold induction of reg Ⅰ receptor in the ductal cells, islets, and acinar cells. These changes suggest that induction of reg Ⅰ and its receptor may be important for recovery from acute pancreatitis.     

胃癌细胞中再生蛋白Ⅰ基因第2内含子的调控功能

目的:观察胃癌细胞中再生蛋白Ⅰ (Reg Ⅰ)基因第2内含子的调控功能.方法:分别从人外周血、胃癌细胞BGC823和SGC7901中提取基因组DNA,克隆Reg Ⅰ第2内含子.构建荧光素酶报告载体pGL4-Human-intron 2、pGL4-BGC823-intron 2和pGL4-SGC7901-intron 2,分别转染胃癌细胞BGC823和SGC7901,荧光检测仪检测荧光素酶活性.结果:RegⅠ基因第2内含子序列与GenBank公布的序列基本一致,但517～531的腺嘌呤A在不同来源的DNA中有差异重复.重组质粒转染胃癌细胞中的萤光素酶活性均高于对照组;转染胃癌细胞来源的intron 2重组质粒,荧光素酶活性低于转染人来源的intron 2.胃泌素孵育后,荧光素酶活性无明显改变.结论:胃癌细胞中Reg Ⅰ第2内含子具有促进基因表达的功能.     

胃癌组织芯片快速制备及RegIV编码产物检测

目的：建立快速胃癌组织芯片（tissuemicroarray,TMA）制作方法,探讨其在RegⅣ编码产物检测和研究中的应用。方法：收集日本富山大学医学部1993-04-20-2010-11-29胃癌石蜡标本372例和相应癌旁黏膜标本（距离癌组织〉4cm）198例,应用AZUMAYA芯片机构建48阵列组织芯片,利用免疫组化和原位杂交检测RegIV蛋白和mRNA的原位表达。在OlympusBX41显微镜下选定切取部位,利用2mm的穿刺针切除供体蜡块,不用制备受体蜡块,直接将切除组织放入金属包埋皿的固定盒上制备48阵列芯片。结果：组织芯片经HE染色确定了组织病理学诊断,免疫组化和原位杂交均发现在肠上皮化生和黏液分泌性肿瘤细胞质中存在RegⅣ蛋白和tuRNA表达。胃黏膜肠化生中RegⅣ蛋白表达为100％（63／63）,高于胃炎的29．0％（27／93,χ^2=73．67,P〈0．001）、腺瘤的85．7％（36／42,χ^2=9．54,P〈0．005）和胃癌的45．2％（168／372,χ^2=65．06,P〈0．001）。胃癌组织中,印戒细胞癌阳性率为95．3％（41／43）,高于低分化癌的27．4％（32／117）,χ^2=55．89,P〈0．001。原位杂交发现,癌旁黏膜肠化生上皮细胞中RegIVmRNA表达阳性率为95．2％（40／42）,高于癌旁正常黏膜的38．6％（17／44,χ^2=30．63,P〈0．001）和胃癌的20．3％（14／69,X2=55．74,P〈0．001）。结论：制备TMA不需要制备受体蜡块,提高了TMA制作速度。异常RegⅣ表达与胃黏膜肠化生球样异型增生-印戒细胞癌的发生途径关系密切。