AP-1在腋臭患者发病过程中的作用

目的：腋臭是美容整形外科的常见病,目前发病机制尚不明确,已证实人体大汗腺中的载脂蛋白D（ApoD）在腋臭患者大汗腺中高表达,并且与腋臭的发生密切相关。探明ApoD在大汗腺细胞中的信号转导通路,可以进一步明确其在腋臭发病过程中的作用机制。JNK信号转导通路与多种疾病的发生有关。课题组前期已经做了JNKl对ApoD调控作用的相关研究,证明了在腋臭发病过程中JNK1是通过调控ApoD的转录来上调ApoD的表达。本实验在课题组前期研究基础上,探讨JNKl下游转录因子AP-1是否在JNKl上调ApoD通路中发挥作用。方法：取腋臭志愿者腋区皮肤组织,进行汗腺细胞培养。把汗腺细胞分为5．二氢睾酮处理组、5-二氢睾酮联合姜黄素处理组和空白对照3个组,用姜黄素抑制AP-1的活性,通过Real．timePCR实验方法检测ApoD在姜黄素抑制下的表达变化。结果：在姜黄素的抑制下,ApoD表达明显降低。在体外培养汗腺细胞加入5．二氢睾酮联合姜黄素处理后,ApoD的表达量在mRNA水平低于单独的5-二氢睾酮处理组和正常对照组（P〈0．05）。结论：姜黄素抑制了AP．1的活化导致ApoD的表达降低。在腋臭的发病过程中,JNKl的下游转录因子AP-1对ApoD有明显的上调作用。AP-1可能在JNKl上调ApoD这条通路中扮演了很重要的角色,它可能是JNK1和ApoD的中间转录因子。     

问题解答

问 :为什么有人会有狐臭 ?答 :狐臭又称腋臭 ,医学上叫“臭汗症”。主要发生在腋下、外生殖器、肚脐和乳头周围等部位。患者的汗液有一种刺鼻难闻的特殊臭味。臭味是怎样产生的呢 ?我们人身上有两种汗腺。一种叫小汗腺 ,除了在唇红缘、小阴唇和阴茎头等处没有以外 ,在全身表面其他各处都有分布。人出生后 ,小汗腺就有分泌汗液的功能。这种汗液主要是水分 ,没有臭味。小汗腺的功能受气温和植物性神经的控制。另一种叫大汗腺 ,分布于腋下、外生殖器 ,肚脐和乳头周围等部位。大汗腺的发育受性激素控制 ,青春期后 ,大汗腺的分泌活动增强。它分泌…     

MRP8蛋白在腋臭中的表达及其意义

为了比较腋臭患者与正常人顶泌汗腺中MRP8表达情况,并对其临床应用价值作出评价。随机选取我院2015～2016年就诊患者90例对其进行回顾性研究,其中腋臭病确诊患者30例作为实验组,肺癌患者30例为阳性对照组,正常人腋下皮肤组织30例作为空白对照组,采用免疫组化法检测MRP8蛋白的表达情况并作统计学分析。实验显示:实验组腋臭顶泌汗腺中MRP8的表达阳性率(60%)高于空白对照组(33.3%),差异具统计学意义(p<0.05);阳性对照组中MRP8的表达阳性率(90%)高于实验组,两组间差异具统计学意义(p<0.05)。腋臭患者的汗腺中MRP8蛋白表达较正常人高,提示腋臭的发生、发展与该蛋白表达的变化具有密切关系,能够为腋臭临床诊断提供重要依据。     

三阴性乳腺癌组织AR、MMP-9、E-cadhenrin表达与临床病理特征及预后的关系研究

摘要 目的：探讨三阴性乳腺癌（TNBC）组织雄激素受体（AR）、基质金属蛋白酶9（MMP-9）、E-钙黏蛋白（E-cadhenrin）表达与临床病理特征及预后的关系。方法：选取2014年1月至2017年1月徐州医科大学附属沭阳医院收集的91例TNBC患者手术切除的癌组织和癌旁组织以及61例乳腺增生组织（对照组）石蜡标本，免疫组化法检测AR、MMP-9、E-cadhenrin表达情况。分析AR、MMP-9、E-cadhenrin表达与TNBC患者临床病理参数之间的关系，Kaplan-Meier生存曲线、COX风险比例回归分析AR、MMP-9、E-cadhenrin表达与TNBC患者预后的关系。结果：TNBC癌组织中MMP-9阳性表达率高于癌旁组织和对照组，AR、E-cadhenrin阳性表达率低于癌旁组织和对照组（P<0.05）。AR表达与分化程度、组织学分级、淋巴结状态有关，MMP-9表达与组织学分级、淋巴结状态、Ki-67表达有关，E-cadhenrin表达与组织学分级、淋巴结状态有关（P<0.05）。Kaplan-Meier生存分析结果显示MMP-9阳性表达患者生存率均低于MMP-9阴性表达患者，AR、E-cadhenrin阴性表达患者生存率均低于AR、E-cadhenrin阳性表达患者（P<0.05）。COX风险比例回归分析结果显示淋巴结状态N1-2、MMP-9阳性表达、AR、E-cadhenrin阴性表达是TNBC患者预后不良的危险因素（P<0.05）。结论：MMP-9过度表达和AR、E-cadhenrin表达缺乏与TNBC患者肿瘤恶性侵袭行为和预后不良有关，评价AR、MMP-9、E-cadhenrin表达状态可为TNBC患者预后预测提供一定的依据。     

慢性重度乙型肝炎患者肝组织中NF-κ Bp65和Caspase-3的表达及其意义

目的:探讨慢性重度乙型肝炎患者肝组织中NF-κBp65和Caspase-3的表达及其意义.方法:选择慢性重度乙型肝炎肝组织标本68例(慢重肝组),正常肝组织标本20例(对照组).采用免疫组化方法检测肝组织中NF-κBp65和Caspase-3的表达.结果:慢重肝组患者肝组织中NF-κBp65和Caspase-3阳性表达程度均明显强于对照组(P＜0.05);慢重肝患者死亡组肝组织中NF-κBp65和Caspase-3阳性表达程度均明显强于存活组(P＜0.05).Spearman相关分析发现,慢重肝组患者肝组织中NF-κBp65和Caspase-3表达之间有明显的正相关性(r=0.449,P＜0.05).结论:NF-κBp65和Caspase-3可能参与了慢性重度乙型肝炎的肝细胞凋亡过程,且具有一定相关性,并对判断患者预后有重要临床价值.     

癫痫患者额叶及颞叶脑组织A型GABA受体α_1亚型基因表达定量研究

为研究A型GABA受体α1亚型(GABRA1)在癫痫患者病灶额叶及颞叶脑组织中的表达变化与癫痫发病机制的关系,采用TaqMan探针荧光定量PCR检测GABRA1在癫痫患者病灶额叶和颞叶脑组织及对照组额叶和颞叶脑组织中的表达量的差异.结果表明,对照组及癫痫患者额叶GABRA1平均相对表达强度为3.785±1.444和4.399±2.89,两者间无显著差异(P>0.05).对照组颞叶脑组织中GABRA1平均表达量是癫痫患者的4.5倍,对照组及癫痫患者颞叶GABRA1平均相对表达强度为26.802±8.983和5.986±5.07,结果具有统计学意义(P<0.05).提示,难治性癫痫患者GABRA1表达在不同组织中的改变并非单一性改变,GABRA1表达量的改变导致癫痫的发生存在组织特异性;GABRA1在颞叶脑组织中的表达减少与癫痫的发生,尤其是难治性癫痫的发生有密切的关系,可能是难治性癫痫致病的因素之一.该研究结果为进一步研究癫痫的发病机制及防治提供了科学依据.     

人膝骨关节炎软骨下骨OPN的表达及其意义

目的:通过检测人膝骨关节炎裸露软骨下骨中OPN的表达,探讨OPN在OA发病及病情进展中的意义。方法:选取接受膝关节置换手术的膝关节骨关节炎患者软骨下骨标本50例,采用综合评分法对OA患者进行严重程度分级,分为轻、中、重度三组,取正常膝关节软骨下骨(股骨髁关节面)10例作为正常软骨下骨对照;对标本进行免疫组织化学染色,用SPSS 17.0统计软件包分析各组间OPN表达的差异及OA患者OPN表达与综合评分、K-L分期的相关性。结果:人膝骨关节炎裸露软骨下骨OPN表达明显高于正常软骨下骨组,差异有统计学意义(P<0.01);OPN在轻、中、重度膝骨关节炎裸露软骨下骨的表达差异有统计学意义(P<0.05);膝骨关节炎裸露软骨下骨OPN的表达与骨关节炎的综合评分、K-L分期呈正相关。结论:OA患者膝关节软骨下骨OPN表达与疾病严重程度呈正相关,提示OPN在骨关节炎发病及病情进展中可能起作用。     

FXR在糖尿病大鼠回肠的表达水平及意义

目的:探索法尼酯衍生物受体(farnesoid X receptor,FXR)在链脲佐菌素(Streptozotocin,STZ)诱导的1型糖尿病(diabetes mellitus,DM)大鼠模型回肠组织中的表达水平及意义。方法:将大鼠随机分为正常对照组(NC组)和DM模型组(DM组)。腹腔注射STZ建立DM大鼠模型,NC组予无水乙醇生理盐水溶液腹腔注射。通过实时荧光定量PCR检测FXR在回肠组织m RNA表达水平。结果:(1)DM组FXR m RNA表达量减少、糖化血红蛋白升高、平均血糖升高、体重下降与NC组之间的差异有统计意义(P0.05);(2)FXR m RNA表达量pearson相关分析:DM组平均血糖、糖化血红蛋白、最终体重与最高体重相比下降的程度、最终体重与造模时体重相比下降的程度与FXR m RNA表达量呈负相关;(3)FXR m RNA表达量多元线性回归分析:DM组平均血糖、最终体重与最高体重相比下降的程度、糖化血红蛋白对FXR m RNA表达量的影响大(P0.05),而NC组各个指标对FXR m RNA表达量无影响(P0.05)。结论:FXR表达异常与糖尿病的发病和糖尿病患者的体重下降相关。     

癫痫患者额叶及颞叶脑组织A型GABA受体α1亚型基因表达定量研究

为研究A型GABA受体α₁亚型(GABRA1)在癫痫患者病灶额叶及颞叶脑组织中的表达变化与癫痫发病机制的关系, 采用TaqMan探针荧光定量PCR检测GABRA1在癫痫患者病灶额叶和颞叶脑组织及对照组额叶和颞叶脑组织中的表达量的差异. 结果表明, 对照组及癫痫患者额叶GABRA1平均相对表达强度为3.785±1.444和4.399±2.89, 两者间无显著差异(P>0.05). 对照组颞叶脑组织中GABRA1平均表达量是癫痫患者的4.5倍, 对照组及癫痫患者颞叶GABRA1平均相对表达强度为26.802± 8.983和5.986±5.07, 结果具有统计学意义(P<0.05). 提示, 难治性癫痫患者GABRA1表达在不同组织中的改变并非单一性改变, GABRA1表达量的改变导致癫痫的发生存在组织特异性; GABRA1在颞叶脑组织中的表达减少与癫痫的发生, 尤其是难治性癫痫的发生有密切的关系, 可能是难治性癫痫致病的因素之一. 该研究结果为进一步研究癫痫的发病机制及防治提供了科学依据.     

新疆食管癌中Myc、TP53表达及其与临床病理因素相关性研究

目的:检测Myc和TP53在食管癌组织和远端无癌组织的表达情况,并分析其与临床病理因素之间的关系,初步探讨Myc和TP53在新疆食管癌发生发展中可能存在的特点。方法:经Trizol一步法提取88例新疆地区食管癌组织及其远端无癌组织标本总RNA,m RNA逆转录为c DNA,经聚合酶链式反应生成产物,运用光密度值即半定量RT-PCR技术检测88例新疆地区食管癌组织、远端无癌组织中Myc和TP53的m RNA表达情况及二者阳性表达率,并分析Myc和TP53的表达与临床病理因素之间的相关性。结果:1 Myc的m RNA相对表达量在食管癌组织中高于远端无癌组织,差异有显著性(P0.01);TP53的m RNA相对表达量在远端无癌组织中高于癌组织(P0.05);2 Myc的阳性表达率在88例食管癌组织中高于远端无癌组织(P0.05);TP53的阳性表达率在远端无癌组织中高于癌组织(P0.05);3Myc的表达与分化程度(P0.01)、TNM分期(P0.01)、淋巴结转移(P0.05)、侵犯深度(P0.05)和族别(P0.05)有关,与性别无关;TP53的表达与侵犯程度(P0.01)有关,与性别、分化程度、TNM分期、淋巴结转移和族别均无关;4 88例食管癌组织中,Myc和TP53的表达呈现负相关(r=-0.501,P0.0 1)。结论:Myc在新疆地区食管癌组织中表达上调,TP53则表达减弱。说明Myc参与食管癌的发生和发展,而TP53则可能保护正常组织不发生癌变。     

Increased JNK1 activity contributes to the upregulation of ApoD in the apocrine secretory gland cells from axillary osmidrosis

Axillary osmidrosis is a benign disorder that causes functional and emotional problems in Asian patients. Recently, ApoD has been identified as an axillary odorant binding protein. The present study was designed to compare the expression of ApoD in normal and osmidrosis subjects. Compared with the normal subjects, osmidrosis subjects had a higher expression of AR and ApoD in the apocrine samples, both at mRNA and protein level. Further study showed that, consistent with the increased ApoD and AR, phosphorylated JNK1 was higher in apocrine samples from axillary osmidrosis subjects, while with no obvious differences of the total expression of JNK1. In the cultured apocrine epithelial cells from normal subjects, 5α-dihydrotestosterone (5α-DHT) increased the expression of ApoD in a dose dependent manner, which can be inhibited by the JNK1 inhibitor. In contrast, in the cultured apocrine epithelial cells from axillary osmidrosis subjects, inhibition of JNK1 significantly reduced the expression of ApoD. Taken together, our study here revealed that increased JNK1 activation in the apocrine cells from axillary osmidrosis contributes to the increased ApoD expression, which in turn involved in the process of axillary osmidrosis.     

Is the treatment of axillary osmidrosis with liposuction better than open surgery?

Axillary osmidrosis is an annoying, although not life-threatening, problem that includes unpleasant odor and the occasional staining of clothing. Suction-assisted lipectomy has been tested as a treatment for axillary osmidrosis with variable success. The authors retrospectively reviewed 134 patients who underwent superficial liposuction for bilateral axillary osmidrosis in their division between June of 1998 and June of 2002. The surgical complications and results were compared with those reported in their previous report of 343 patients (102 available for postoperative result evaluation) who received open surgical treatment with partial excision of axillary skin and subcutaneous tissue. The overall complication rate was 3.73 percent, significantly lower than the 11.08 percent complication rate seen with open surgical treatment. Of their 134 patients, 114 were available for long-term follow-up. Thirteen patients (11.40 percent) had very good results, 79 patients (69.30 percent) had good results, and 22 patients (19.30 percent) had poor results. Significant differences were found between those who underwent superficial liposuction and those who underwent open surgery. The number of patients with very good and good results decreased significantly from 91.18 percent (open surgery) to 80.70 percent (liposuction), and those with little or no improvement increased from 8.82 percent (open surgery) to 19.29 percent (liposuction). Compared with open surgery for the treatment of osmidrosis, liposuction produces significantly fewer complications but is less effective. Of the patients who underwent liposuction for osmidrosis, 80 percent were satisfied with the result. Further study is needed to determine whether liposuction for osmidrosis can be improved.     

miR-19a 在正常妊娠及重度子痫前期患者胎盘中的表达

目的:通过检测正常妊娠及重度子痫前期患者胎盘组织中miR-19a的表达,探讨其与子痫前期发病的关系。方法:收集10例重度子痫前期患者胎盘组织(实验组)和10例正常产妇胎盘组织(对照组),应用荧光实时定量PCR(Real Time PCR)的方法检测两组miR-19a的表达差异。结果:重度子痫前期患者胎盘组织中miR-19a表达升高(P<0.05)。结论:子痫前期患者胎盘组织中存在差异表达的miRNA,miR-19a在胎盘组织中的高表达可能与子痫前期的发病有关。     

外周血单核细胞CD58和CD58mRNA表达与HBV感染关系的研究

为了探讨PBMCCD58(LFA3)表达与乙型肝炎病毒感染关系,应用逆转录荧光定量聚合酶链反应(RTFQPCR)法和流式细胞术分别检测43例HBV感染者(慢性肝炎轻度组12例,中度组11例,重度组10例,重型乙型肝炎组10例)和11例正常对照的外周血单核细胞(PBMC)CD58mRNA及CD58+细胞百分率的水平,同时检测血清ALT、AST水平。结果显示,乙型肝炎各组患者PBMCCD58mRNA及CD58+细胞百分率水平较正常对照组明显增高,差异均有显著性(P<0.05);CD58水平由低到高依次分别为慢性乙型肝炎轻度组、中度组、重度组及重型乙型肝炎组,各组患者间相比较,差异亦有显著性(P<0.05);乙型肝炎患者PBMCCD58mRNA及CD58+细胞百分率水平与血清ALT、AST呈显著正相关。因此,乙型肝炎患者PBMCCD58mRNA及CD58+细胞百分率水平与疾病严重程度及肝细胞损伤严重程度有关。     

Testosterone inhibits estrogen-induced mammary epithelial proliferation and suppresses estrogen receptor expression.

This study investigated the effect of sex steroids and tamoxifen on primate mammary epithelial proliferation and steroid receptor gene expression. Ovariectomized rhesus monkeys were treated with placebo, 17beta estradiol (E2) alone or in combination with progesterone (E2/P) or testosterone (E2/T), or tamoxifen for 3 days. E2 alone increased mammary epithelial proliferation by approximately sixfold (P:<0.0001) and increased mammary epithelial estrogen receptor (ERalpha) mRNA expression by approximately 50% (P:<0.0001; ERbeta mRNA was not detected in the primate mammary gland). Progesterone did not alter E2's proliferative effects, but testosterone reduced E2-induced proliferation by approximately 40% (P:<0.002) and entirely abolished E2-induced augmentation of ERalpha expression. Tamoxifen had a significant agonist effect in the ovariectomized monkey, producing a approximately threefold increase in mammary epithelial proliferation (P:<0.01), but tamoxifen also reduced ERalpha expression below placebo level. Androgen receptor (AR) mRNA was detected in mammary epithelium by in situ hybridization. AR mRNA levels were not altered by E2 alone but were significantly reduced by E2/T and tamoxifen treatment. Because combined E2/T and tamoxifen had similar effects on mammary epithelium, we investigated the regulation of known sex steroid-responsive mRNAs in the primate mammary epithelium. E2 alone had no effect on apolipoprotein D (ApoD) or IGF binding protein 5 (IGFBP5) expression, but E2/T and tamoxifen treatment groups both demonstrated identical alterations in these mRNAs (ApoD was decreased and IGFBP5 was increased). These observations showing androgen-induced down-regulation of mammary epithelial proliferation and ER expression suggest that combined estrogen/androgen hormone replacement therapy might reduce the risk of breast cancer associated with estrogen replacement. In addition, these novel findings on tamoxifen's androgen-like effects on primate mammary epithelial sex steroid receptor expression suggest that tamoxifen's protective action on mammary gland may involve androgenic effects.     

Expression of osteoprotegerin in placenta and its association with preeclampsia

Background

Osteoprotegerin (OPG), a key regulatory factor in bone metabolism, was documented also a potential pro-angiogenic factor, which acts an important role in protecting vascular endothelial cells. Since preeclampsia has gradually been employed to be vascular diseases, we speculated that OPG might be associated with preeclampsia. The study was to evaluate the level of OPG protein and mRNA in placenta, and investigate the relationship between OPG and the pathogenesis of preeclampsia.

Methodology/Principal Findings

Placental specimens from 30 term normal pregnancy, 30 severe preeclampsia and 30 mild cases were studied. The expression and levels of OPGs’ protein and mRNA were detected by immunohistochemisty, western blot analysis and real-time quantitative PCR analysis respectively. The expression of OPG protein was found in cytoplasm of placenta cytotrophoblasts and syncytiotrophoblasts in three groups. There were no significant differences of OPG protein between the maternal and fetal side in each group. The OPG protein and mRNA levels in severe preeclampsia were significantly higher than those in mild cases and normal pregnancy. However, there were no markedly differences of the OPG protein and mRNA levels between term delivery and preterm delivery in severe cases. In preeclampsia, the OPG protein and mRNA level was positively correlated with systolic blood pressure and 24 h urinary protein respectively.

Conclusions/Significance

OPG protein and mRNA level in placentas of preeclampsia were found abnormal compared with normal pregnancy. In preeclampsia, the OPG protein and mRNA levels were closely related with its important clinical parameters. Taken together, OPG might be closely correlated with the pathogenesis of preeclampsia.     

miR-19a在正常妊娠及重度子痫前期患者胎盘中的表达

目的：通过检测正常妊娠及重度子痫前期患者胎盘组织中miR-19a的表达,探讨其与子痫前期发病的关系。方法：收集10例重度子痫前期患者胎盘组织（实验组）和10例正常产妇胎盘组织（对照组）,应用荧光实时定量PCR（Real Time PCR）的方法检测两组miR-19a的表达差异。结果：重度子痫前期患者胎盘组织中miR-19a表达升高（P〈0.05）。结论：子痫前期患者胎盘组织中存在差异表达的miRNA,miR-19a在胎盘组织中的高表达可能与子痫前期的发病有关。     

rRNA-based profiling of bacteria in the axilla of healthy males suggests right-left asymmetry in bacterial activity

The activity of the human armpit microbiota triggers the formation of body odor. We used differential 16S rRNA gene (rDNA)- and rRNA-based terminal-restriction fragment length polymorphism fingerprinting in combination with cloning and sequencing to identify active members of the human armpit microbiota. DNA and RNA were isolated from skin scrub samples taken from both armpits of 10 preconditioned, healthy males. The fingerprint profiles indicated pronounced similarities between the armpit microbiota in the right and the left axillae of an individual test person, but larger differences between the axilla microbiota of different individuals. Using 16S rDNA and rRNA sequence data, the majority of peaks in the armpit profiles were assigned to bacteria affiliated with well-known genera of skin bacteria. The relative abundances of all groups were similar among the rDNA and rRNA samples, suggesting that all groups of armpit bacteria were active. Surprisingly, the relative abundance of sequences affiliated with Peptoniphilus sp. was by far and with statistical significance the highest in the rRNA samples of the right armpits. Thus, bacteria affiliated with Peptoniphilus sp. might have been particularly active in the right axillae of the test persons, possibly owing to the handedness of the test persons, which might cause different environmental conditions in the right axillae.