Responses of CDKs and p53 in Delayed Ischemic Neuronal Death

Stroke is a debilitating disease that affects millions each year.While in many cases cerebral ischemic in jury can be limited by effectivw resuscitation or thrombolytic treatment,the injured neurons wither in a process known as delayed neuronal death(DND).Mounting evidence indicates that DND is not simply necrosis played out in slow motion but apoptosis is triggered.Of particular interest are two groups of signal proteins that participate in apoptosis-cyclin dependent kinases(CDKs) and p53-among a myriad of signaling events after an ischemic insult.Recent investigations have shown that CDKs,a family of enzymes initially known for their role in cell cycle regulation,are activated in injured neurons in DND.As for p53,new reports suggest that its up-regulation may represent a failed attempt to rescue in jured neurons,although its up-regulation was previously considered an indication of apoptosis.These observations thus rekindle an old quest to identify new neuroprotective targets to minimize the stroke damage.In this review,the author will examine the evidence that indicates the participation of CDKs and p53 in DND and then introduce pre-clinical data to explore CDK inhibition as a potential neuroprotective target.Finally,using CDK inhibition as an example,this paper will discuss the pertinent criteria for a viable neuroprotective strategy for ischemic in jury.     

人发中铜的分析研究

发样用HN03-HCO04加热消化，然后用BAO分光光度法直接测微量铜，T（4-TAP）P法测痕量铜。方法的准确度用不同方法对照分析的结果比对，所得结果准确可靠，应用BAO法测定人发、粉尘和尿铜，弄清了发铜的含量水平，铜污染的来源及其迁移，从而为微量铜与健康的研究，环境污染防治以及发铜的标准参照测试提供科学依据。     

Overexpression of S100A4 is closely related to the aggressiveness of gastric cancer

Elevated levels of the calcium-binding protein S100A4 cause metastasis of benign rat mammary tumor cells. To investigate whether S100A4 plays an important role in the invasion and metastasis of gastric cancers, we examined the gene mutations in the coding regions and expression patterns of the S100A4 in gastric adenocarcinoma in Korea. Moderate to strong expression of S100A4 was found in 53 (68.8%) of the 77 gastric adenocarcinomas, whilst normal gastric epithelium either failed to stain or showed weak staining. Interestingly, S100A4 expression was more frequently observed in gastric cancer patients with advanced gastric cancer (p=0.039), positive lymph node metastasis (p=0.001), and peritoneal dissemination (p=0.022). No gene mutations were found in the analyzed genomic area in 77 gastric adenocarcinomas and 15 gastric cancer cell lines. We found one single nucleotide polymorphism without an amino acid change, A99G, in two cases. These data suggest that the overexpression of S100A4 may be closely related to the aggressiveness of gastric cancer in Korea.     

Analysis of microdissected prostate tissue with ProteinChip arrays--a way to new insights into carcinogenesis and to diagnostic tools

Prostate carcinomas are one of the most common malignancies in western societies. The pathogenesis of this tumor is still poorly understood. These tumors present with two characteristic features: epithelial-mesenchymal interactions, which play a pivotal role for tumor development and most of clinically manifest cancers arise in prostate proper compared to a minority of tumors which develop in the transitional zone. Deciphering the epithelial-mesenchymal cross talk and identification of molecular pecularities of the sub-populations of cells in different zones can therefore help understanding carcinogenesis and development of new, non-invasive tools for the diagnosis and prognosis of prostate carcinomas which has remained a challenge until today. A ProteinChip array technology (SELDI = surface enhanced laser desorption ionization) has been developed recently by Ciphergen Biosystems enabling analysis and profiling of complex protein mixtures from a few cells. This study describes the analysis of approximately 500-1000 freshly obtained prostate cells by SELDI-TOF-MS (surface enhanced laser desorption ionization time-of-flight mass spectrometry). Pure cell populations of stroma, epithelium and tumor cells were selected by laser assisted microdissection. Multiple specific protein patterns were reproducibly detected in the range from 1.5 to 30 kDa in 28 sub-populations of 4 tumorous prostates and 1 control. A specific 4.3 kDa peak was increased in the prostate tumor stroma compared to normal prostate proper and transitional zone stroma and increased in prostate tumor glands compared to normal prostate proper and transitional zone glands. Coupling laser assisted microdissection with SELDI provides tremendous opportunities to identify cell and tumor specific proteins to understand molecular events underlying prostate carcinoma development. It underlines the vast potential of this technology to better understand pathogenesis and identify potential candidates for new specific biomarkers in general which could help to screen for and distinguish disease entities, i.e. between clinically significant and insignificant carcinomas of the prostate.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Diagnostic accuracy of Raman spectroscopy for prostate cancer: a systematic review and meta-analysis

BackgroundAlthough various studies have been conducted to demonstrate the possibility of Raman spectroscopy (RS) as a diagnostic tool for prostate cancer (PC), it is difficult to use it in the real clinical area because of imitations in various research processes. Therefore, we did a systematic review and meta-analysis about the accuracy in diagnostic use of RS for PC.MethodsA literature search was done using PubMed, Embase, and Cochrane library databases in March 2019 to analyze the accuracy of RS for diagnosis of PC. The accuracy of RS for diagnosis of PC was evaluated by means of pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC).ResultsFive studies were included for qualitative analysis by screening the remaining articles according to the inclusion and exclusion criteria by means of a systematic review. The pooled sensitivity and specificity of RS were 0.89 (95% CI: 0.87–0.91) and 0.91 (95% CI: 0.89–0.93), respectively. The overall PLR and NLR were 9.12 (95% CI: 4.15–20.08) and 0.14 (95% CI: 0.07–0.29), respectively. The DOR of RS demonstrated high accuracy (73.32; 95% CI: 18.43–291.73). The area under the curves (AUCs) of SROC curves was 0.93.ConclusionsRS is an optical diagnostic method with high potential for diagnosis and grading of PC and has advantages of real-time and convenient use. In order to consider real-time use of RS in an actual clinical setting, more studies for standardization and generalization of RS performance and analytical method must be conducted.     

常温下肝脏缺血/再灌注损伤及其机制的实验研究

目的　研究常温下肝脏缺血 /再灌注损伤及其机制。方法　 2 4只兔随机均分为缺血组和对照组。组织气体分析仪持续测定兔肝组织氧压 (HepatictissueoxygeonpressurePtiO2 ) ;光镜及电镜观察肝脏组织病理改变 ;全自动生化仪测定血清丙氨酸氨基转氨酶 (ALT)。结果　缺血组兔肝脏在缺血后肝PtiO2 值开始下降、30min降至 2 0 1± 2 8,再灌注后的肝PtiO2 值开始恢复 ,再灌注 6 0min肝PtiO2 未恢复正常 (P <0 0 5 )。肝细胞出现变性、坏死 ,血清ALT值显著升高 ,在肝脏再灌注 6 0min时最为严重。结论　常温下用Pringle氏法阻断入肝血流可导致肝脏缺血/再灌注后肝细胞功能障碍和病理损害。其作用机制与缺血期肝细胞缺氧、再灌注期肝脏微循环障碍和肝细胞线粒体的损伤有关。