肾母细胞瘤与胚胎肾发育及肾源性剩余的关系

目的 探讨肾母细胞瘤发生与胚胎肾分化发育及肾源性剩余的关系。方法 在光学显微镜下比较３０例肾母细胞瘤和１６例不同胎龄肾组织的形态特点;观察比较２２例肾母细胞瘤瘤旁肾组织和３０例非肿瘤成熟肾组织中肾源性剩余的阳性率。结果 肾母 细胞瘤与早期胚胎肾在组织形态上有相似之处;２２例肾母细胞瘤瘤旁肾组织中６例见肾源性剩余存在,３０例非肿瘤成熟肾组织中仅１例见肾源性剩余存在。结论 肾母细胞瘤的发生与胚胎肾分化     

Leptin受体在人胚胎皮肤附件发育过程中的表达特征

目的:探讨Leptin受体在人胚胎皮肤形成和附件发育过程中的表达特点及可能的生物学意义。方法:取8-38周龄人胚胎的背部全层皮肤,制成石蜡切片．进行常规组织学观察和免疫组织化学染色(SP法),动态观察皮肤形成过程和附件发育过程中Leptin受体的表达特点。结果:胚胎8周开始,胎儿周皮已有Leptin受体表达,随后逐渐增强。至胚胎11-16周表达最强,尤其在附件原基中呈局灶性表达;胚胎22周后,Leptin受体的表达逐渐减弱,至胚胎31周后仅在皮脂腺中表达。结论:Leptin可能通过其受体参与皮肤附件的发育过程。     

生长抑素受体2在结直肠癌中表达与预后的关系

目的 研究生长抑素受体2（SSTR2）表达与结直肠癌患者预后的关系.方法 采用免疫组织化学染色检测121例结直肠癌组织中的SSTR2表达,并采用Cox比例风险模型分析SSTR2表达与结直肠癌预后的关系.结果 本组121例结直肠标本中SSTR2低表达58例（47.9%）,高表达63例（52.1%）.接受随访的111例患者5年总体生存率为70%,其中SSTR2低表达者为53%,明显低于高表达者（83%,P＜0.01）.多因素预后分析证实,SSTR2表达是本组患者的独立预后因素（均P＜0.05）.结论 SSTR2表达有可能成为一项新的生物学预后指标.     

联合检测诱骗受体-3和白细胞介素-17在人脑胶质瘤的表达及意义

目的 探讨诱骗受体-3(DcR-3)和白细胞介素-17(IL-17)在人脑胶质瘤中的表达及意义.方法 连续收集90例胶质瘤患者及脑外伤患者10例,应用酶联免疫吸附试验(ELISA)试剂盒检测各组血清DcR-3和IL-17浓度,Western blot和免疫荧光染色方法检测脑组织中的DcR-3和IL-17蛋白的表达.结果 胶质瘤患者DcR-3和IL-17在不同的性别、年龄中表达差异无统计学意义(P＞0.05),但与肿瘤病理分级有关,Ⅲ/Ⅳ级胶质瘤患者DcR-3和IL-17表达阳性例数明显高于Ⅰ/Ⅱ级患者(P＜0.01).绝大多数胶质瘤患者DcR-3表达升高伴有IL-17表达阳性.不同级别(Ⅰ、Ⅱ、Ⅲ、Ⅳ)的胶质瘤患者术前血清DcR-3和IL-17浓度均明显高于对照组(P＜0.01).术后DcR-3和IL-17浓度显著降低,Ⅰ～Ⅳ级的胶质瘤患者术前术后DcR-3和IL-17比较差异均有统计学意义(P＜0.01).术前血清DcR-3和IL-17水平与胶质瘤患者预后复发和存活密切相关.存活组胶质瘤患者血清DcR-3和IL-17平均浓度分别为(56.22±18.33)和(72.89士16.58)ng/L,显著低于死亡组[DcR-3和IL-17平均浓度分别为(103.27±10.47)和(121.00±9.02)ng/L,P＜0.01].结论 DcR-3和IL-17表达与人脑胶质瘤的病理分级呈正相关,联合检测血清DcR-3和IL-17浓度有助于胶质瘤患者的诊断、疗效观察和预后判断.     

移植肾白细胞介素2受体的表达及其临床意义

我们连续观察了７１例１７５次同种异体尸体肾移植患者移植肾白细胞介素２受体（ＩＬ－２Ｒ）表达的变化，探讨其在肾移植排斥反应诊断及鉴别诊断中的意义。一、临床资料１．病例选择：７１例异体肾移植患者，术后常规应用环孢素（ＣｓＡ）、泼尼松（Ｐｒｅｄ）和硫唑嘌呤...     

高表达蛋白hSav1对人胚肾HEK293增殖能力的影响

目的 观察高表达人Salvadorl(hSav1)蛋白对人胚肾293(HEK293)细胞增殖的影响.方法 构建含有绿色荧光蛋白(GFP)的hSav1质粒GFP-N1-hSav1;将构建好的GFP-N1-hSav1质粒在脂质体Lipofectamine 2000的介导下转染HEK293细胞,荧光显微镜下观察质粒转染效率;分别在转染后12、24、36、48 h通过噻唑蓝(MTT)比色法计算细胞增殖抑制率,抑制率=[(对照-空白)-(给药-空白)]/(对照-空白)×100%;转染后36 h加入5-溴-2'-脱氧尿苷(BrdU),通过其掺入比率来显示hSav1对细胞增殖的影响.结果 质粒GFP-N1-hSav1构建成功,转染效率为70%-80%左右,蛋白hSav1明显高表达;MTT结果显示转染质粒后12、24、36、48 h,高表达蛋白hSav1组的细胞增殖抑制率分别为2%、5%、15%、23%,而阴性对照分别为2%、3%、2%、2%;BrdU结果显示,在HEK293细胞中高表达蛋白hSav1后细胞增殖抑制率为(27.3±3.8)%,阴性对照组的细胞增殖抑制率为(12.9±5.3)%,差异有统计学意义(P<0.05).结论 在人胚肾HEK293中高表达蛋白hSav1可明显抑制细胞增殖能力.     

高表达蛋白hSav1对人胚肾HEK293增殖能力的影响

Objective To elucidate the effects of human Salvador 1 (hSav1 ) on cell proliferation of human embryonic kidney cell line HEK293. Methods The plasmid CFP-N1-hSav1 was constructed and transfected into HEK293 cells with lipofectamine 2000. The transfection efficiency was detected by fluorescent microscopy. The effects of hSav1 on cell proliferation were measured by MTT and BrdU incorporation. Results The transfection efficiency was about 70% -80%. The MTT results showed that the inhibition rate of cell proliferation in transfected group at the 12th, 24th, 36th, and 48th h was 2% , 5% , 15% , and 23% , respectively;while that in the control group was 2% , 3% , 2% , and 2% respectively. The BrdU incorporation revealed that the BrdU incorporation rate in transfected group (12. 9 ±5. 3)% was significantly lower than in control group (27.3±3.8)% (P<0.05). Conclusion hSav1 is a newly identified protein that can cause cell proliferation inhibition in HEK293 cells.     

高表达蛋白hSav1对人胚肾HEK293增殖能力的影响

Objective To elucidate the effects of human Salvador 1 (hSav1 ) on cell proliferation of human embryonic kidney cell line HEK293. Methods The plasmid CFP-N1-hSav1 was constructed and transfected into HEK293 cells with lipofectamine 2000. The transfection efficiency was detected by fluorescent microscopy. The effects of hSav1 on cell proliferation were measured by MTT and BrdU incorporation. Results The transfection efficiency was about 70% -80%. The MTT results showed that the inhibition rate of cell proliferation in transfected group at the 12th, 24th, 36th, and 48th h was 2% , 5% , 15% , and 23% , respectively;while that in the control group was 2% , 3% , 2% , and 2% respectively. The BrdU incorporation revealed that the BrdU incorporation rate in transfected group (12. 9 ±5. 3)% was significantly lower than in control group (27.3±3.8)% (P<0.05). Conclusion hSav1 is a newly identified protein that can cause cell proliferation inhibition in HEK293 cells.     

人胚肾细胞SGLT2基因异源表达体系的构建

目的 构建钠依赖的葡萄糖转运蛋白2（SGLT2）基因异源表达体系,为探讨突变引起SGLT2蛋白功能及表达异常的分子机制提供实验依据。 方法 利用RT-PCR法从人肾组织中获得SGLT2基因,将该基因克隆到真核表达载体PEXL-GFP（绿色荧光蛋白）中,将携带有SGLT2基因的PEXL载体转染人胚肾细胞系（HEK293细胞）,获得目的蛋白的瞬时表达。应用Western印迹及激光共聚焦显微镜检测融合蛋白在HEK293细胞的表达和分布,并通过摄取实验进一步验证SGLT2蛋白的转运功能。 结果 SGLT2-GFP蛋白可在HEK293细胞表达,激光共聚焦显微镜观察发现,SGLT2-GFP蛋白在细胞膜上呈点状分布,并且与细胞膜标记物（DiI）有良好的共定位,转染SGLT2-GFP质粒的HEK293细胞的转运活性较对照组（未转染及转染空质粒细胞组）强约3.5倍（P < 0.01）。 结论 成功构建了SGLT2真核表达载体,为探讨SGLT2基因表达、功能及SGLT2突变在家族性肾性糖尿发病的遗传机制提供了重要的依据。     

人肾间质纤维母细胞培养及血管紧张素Ⅱ2型受体转染表达

目的：体外培养人肾间质纤维母细胞（hRIF)并用腺病毒介导转染表达血管紧张素Ⅱ（AngⅡ）2型受体（AT2R）。方法：用肾穿刺活检法取慢性肾小球肾炎病人肾组织,以常规组织块贴壁法培养hRIF;构建带AT2R基因的重组复制缺陷型腺病毒载体（AdCMV-AT2R),体外转染hRIF;用RT-PCR方法检测AT2RmRNA表达,免疫组织化学法及蛋白免疫印迹法检测AT2R蛋白表达,流式细胞仪检测AT2R表达0率,同时检测AT1R的表达变化。结果：用肾活检组织成功培养出hRIF,构建的AdCMV-AT2R体外转染培养hRIF表达率为90.57%,以免疫组化、免疫印迹和RT-PCR检测AT2R表明,转染后AT2R表达明显增强。并随表达时间延长而增加,48h为表达峰值。AT2R转染表达不影响AT1R表达,结论：腺病毒载体可较高效率介导AT2R在hRIF的转染表达,ATIR表达不受其影响。转染表达AT2R的hRIF可作为研究AngⅡ在肾间质纤维化中作用的良好细胞模型。     

Aberrant expression of decoy receptor 3 in human breast cancer: relevance to lymphangiogenesis

Background

Decoy receptor 3 (DcR3), a decoy receptor against Fas ligand belonging to the tumor necrosis factor receptor superfamily, is overexpressed in some forms of cancer. It was recently reported that DcR3 could protect endothelial cells from apoptosis, implying a potential role in the development of vessels, whereas its role in the lymphangiogenesis remains unclear. In the present study, we studied the DcR3 expression and its relationship with the lymphatic microvessel density (LMVD) to investigate if it played a role in the lymph metastasis of human breast cancer.

Materials and methods

Real-time polymerase chain reaction and immunohistochemistry were performed to measure the messenger RNA and protein expression of DcR3 in the breast cancer tissues, noncancerous counterparts, and axillary lymph node from 63 patients. LMVD in these specimens was assessed by counting the D2-40 labeled–microvessels. Furthermore, the correlations between DcR3 expression and LMVD and other clinicopathologic parameters were analyzed.

Results

DcR3 was overexpressed in the breast cancer tissue of 58 patients (92.1%) and was also expressed in vascular endothelial cells and tumor cells in the lymph nodes. LMVD in cancer tissue and lymph nodes were both positively correlated to the aberrant expression of DcR3.

Conclusions

The relevance between DcR3 overexpression and LMVD revealed the existence of possible links between DcR3 and lymphangiogenesis. Based on these findings, it is important to further explore the regulation of lymphangiogenesis operated by the reverse tumor necrosis factor signaling of DcR3.     

线粒体DNA拷贝数与胚胎发育潜能的关系

依靠胚胎形态学评分来评价胚胎发育潜能,容易受到人为主观因素的影响。尽管通过胚胎植入前遗传学检测,能够对胚胎染色体非整倍性进行识别,选择染色体整倍性胚胎植入,但还是有很大一部分整倍性的胚胎,即使在内分泌因素适合的条件下,也依然不能获得临床妊娠。这就需要通过新的技术来改善辅助生殖的结局。通过胚胎发育潜能来选择胚胎就是目前最新的研究技术之一。在诸多方法中,通过线粒体DNA含量的评估来预测胚胎发育潜能,获得了广大学者持续性的关注。     

Soluble interleukin 2 receptor (Tac chain) is not a reliable marker in kidney transplant recipient monitoring

T lymphocyte expansion is triggered through interaction of interleukin 2 (IL-2) with its high-affinity receptor (IL-2R). This molecule is a heterodimer comprising an antigen-inducible component, the Tac chain (P55). Activation of T lymphocytes also generates a soluble form of this P55 called S-IL-2R. S-IL-2R is elevated in many T-cell-related pathologies (leukaemia, autoimmunity, etc.). In graft recipients, rejection is a result of T-cell activation by graft antigens and therefore might induce a release of S-IL-2R in the circulation; this parameter is now said to be a good indicator of rejection. We have performed a study in renal graft recipients in order to assess the usefulness of circulating S-IL-2R particularly to discriminate the origin of renal failure in cases of rejection or of cyclosporin-A (CsA)-induced nephrotoxicity. We demonstrated that there are no differences between isolated values in the clinical groups at the time of diagnosis. Variations in S-IL-2R are increased compared to steady-state periods during rejection and cytomegalovirus infections, although not in CsA toxicity episodes. However, at the individual level there are too many false-positive and false-negative results, making this parameter no more meaningful than serum creatinine levels alone or even in association (as tested in logistic discriminant analysis). In addition, it seems that the variations in S-IL-2R are patly related to renal function itself, as suggested by the correlation between S-IL-2R levels and serum creatinine levels. This association may explain the increase in S-IL-2R that can be observed without T cell activation. In conclusion, S-IL-2R may not be of major interest in discriminating between rejection of kidney and CsA-induced nephrotoxicity episodes in kidney allograft recipients.     

Overexpression of toll-like receptor 2 in glomerular endothelial cells and podocytes in septic acute kidney injury mouse model

Abstract

Acute kidney injury (AKI) is one of the most common complications in patients with severe sepsis. The development of septic AKI increases patients’ mobility and even mortality. Toll-like receptor 2 (TLR2), as a membrane surface receptor for bacterial, fungal, viral and certain endogenous substances, has been described to contribute to the development of septic AKI; however, the renal cell types associating TLR2 overactivation in septic AKI has not been described. In the current study, we investigated the TLR2 activation patterns in the kidney of lipopolysaccharide-induced septic AKI mice. Our results demonstrated that mRNA level of TLR2 significantly increased in the kidney of lipopolysaccharide-treated mice. Immunohistochemistry revealed the overactivation of TLR2 in the glomeruli. Double immunofluorescence analysis shows the precise distribution of TLR2 by showing the colocalization of TLR2 in glomeruli with synaptopodin, a podocyte marker, and Tie2, an endothelial marker. In addition, proapoptotic molecules Bax and Caspase-3 were increased in the glomeruli of lipopolysaccharide-treated mice. Together, the current study indicates that TLR2 is overactivated in the glomerular endothelial cells and podocytes in septic AKI mice, while the abundance of Bax and Caspase-3 were increased in the glomeruli of these mice, it may supply a clue that TLR2 induced these cell apoptosis in AKI. This finding provides an alternative mechanism to understand AKI development and potential targets for treatment.     

Cinnamaldehyde attenuates kidney senescence and injury through PI3K/Akt pathway-mediated autophagy via downregulating miR-155

BackgroundTo prove the internal connection, we deciphered the effect of cinnamaldehyde on kidney senescence through establishing animal and cell models.MethodsIn vivo, a rat senescence model was constructed using D-galactose (D-gal), and the modeled rats were further treated with cinnamaldehyde. In vitro, rat renal tubular epithelial cells (NRK-52E) were transfected with miR-155 mimic or inhibitor and then treated with cinnamaldehyde, D-gal or PI3K inhibitor (LY294002). The serum levels of blood urea nitrogen (BUN) and serum creatinine (Scr) of the rats were measured by an automatic biochemical analyzer. Pathological changes of kidney were determined by hematoxylin-eosin staining. The senescence and viability of NRK-52E cells were assessed by SA-β-gal staining and CCK-8 assay, respectively. The levels of miR-155, p-PI3K/PI3K, p-Akt/Akt, LC3B (LC3-II and LC3-I) and Beclin1 were detected by qRT-PCR, immunohistochemistry, or western blot.ResultsD-gal elevated the levels of BUN, Scr and miR-155 in the kidney, induced the renal pathological damage, inhibited the cell viability, increased the numbers of SA-β-gal-, LC3B- and Beclin1-positive cells and upregulated the levels of LC3-II/LC3-I and Beclin1 both in the kidney and cells. Cinnamaldehyde reversed D-gal-induced effects on the kidney and cells, and moreover, the cinnamaldehyde-induced anti-D-gal effects on cells could be suppressed by miR-155 mimic but promoted by miR-155 inhibitor. LY294002 potentiated D-gal-induced effects, and reversed cinnamaldehyde- and miR-155 inhibitor-caused impacts on the PI3K/Akt pathway and LC3-II/LC3-I level in D-gal-induced cells.ConclusionCinnamaldehyde attenuates kidney senescence and injury through PI3K/Akt pathway-mediated autophagy via downregulating miR-155.     

Beta2‐adrenergic receptor in kidney biology: A current prospective

Beta2‐adrenergic receptor (β₂‐AR) is a G‐protein‐coupled adrenergic receptor family member, whose clinical significance has been extensively investigated in lung, cardiovascular and muscular diseases, but its role in kidney biology remains understudied. In this review, we discuss some of the recent studies, where the effect of agonist/antagonist‐mediated activation/inhibition of β₂‐AR on disease pathogenesis process was studied, and highlighted the role of β₂‐AR in kidney biology. The expression of β₂‐AR has been noted in many kidney subunits including proximal tubules, glomeruli and podocytes. In vivo studies have shown that in cultured proximal tubules β₂‐AR is involved in Na‐ATPase activity and transcellular Na‐transport through protein kinase‐C activation; whereas in cultured podocytes, it was associated with depolarization of the membrane. The animal studies further revealed that β₂‐AR activation by short‐acting β₂ agonists attenuated monocyte activation, pro‐inflammatory and pro‐fibrotic responses through β‐arrestin2 dependent NF‐kB inactivation in diabetic kidney disease; in contrast, activation by long‐acting β₂ agonists restored mitochondrial and renal function in the acute kidney injury mice models through PGC‐1α dependent mitochondrial biogenesis. In conclusion, the activation of β₂‐AR may present a rapidly developing therapeutic target for renal diseases.     

芳香烃受体与肿瘤的关系

芳香烃受体是一个配体依赖性激活的转录因子,外源性芳香烃化合物能与其结合并使其激活,从而引起多种代谢酶升高,活性增强,致癌性代谢产物增多,最终导致肿瘤的发生.现就芳香烃受体的基本概念及其与肿瘤的关系作简要综述.     

人类表皮生长因子受体2表达与胃癌组织学的相关性研究

目的 分析内镜下不同活检部位胃癌组织中人类表皮生长因子受体2（HER2）表达阳性率及与胃癌组织学特点相关性。方法 收集本院2017年1月至2020年1月收治的胃癌患者87例列入胃癌组,选取同期住院治疗的慢性浅表型胃炎患者21例列入正常胃黏膜组,入院后将内镜或手术获得的标本行病理检查,比较内镜标本中不同活检部位组织的HER2阳性率和胃癌病理学特征与人类表皮生长因子受体2表达水平的关系。结果 胃癌组HER2阳性率较胃黏膜正常组更高（17.2%和0.0%,P<0.05）,内镜下肿瘤浅表弥漫部、溃疡隆起部、溃疡床及肿块突起部组织HER2阳性率分别是100%、90%、44%、100%,病理类型为管状腺癌及镜下不含印戒细胞较其他组织类型癌和镜下含印戒细胞HER2阳性率高（分别是23.0%、23.6%和3.8%、6.3%,P<0.05）。结论 胃癌HER2表达水平与其病理组织学特点具有相关性,镜下不含印戒细胞的胃癌组织HER2阳性率可能更高,在评估内镜活检标本HER2表达时应着重选择肿瘤浅表弥漫部和肿块突起部,可以为胃癌靶向治疗提供参考。