美国发现一氧化氮可定细胞生死

美国杜克大学医学中心的研究人员近日发现,一氧化氮分子对负责指导细胞最基本活动的蛋白质网络具有“召集”作用,这些蛋白质往往能够决定细胞的生与死。

细胞存活信号和细胞生死的群体控制

程控性细胞死亡（ＰＣＤ）是细胞死亡的一种特殊形式。当细胞完成其功能使命，或遭受严重伤害，或发生异常时，由各种细胞内外信号分子激活细胞所固有的自杀程序而导致细胞死亡。ＰＣＤ的调节控制是由于某种缺失所引起的，即细胞不能接受对细胞内在的自杀程序有抑制作用的...

细胞凋亡与生殖

通过改变基因的表达或激素水平 ,可人为地调节生殖细胞的凋亡 ,对于了解生殖系统疾病及其本质和防治方法具有非常重要的意义。本文就生殖细胞凋亡的现象。

鞍区生殖细胞瘤3例报告及文献复习

本文通过3例鞍区生殖细胞瘤的诊治及文献复习，提出对鞍区生殖细胞瘤的治疗，由于周围重要的神经结构，外科手术应以明确诊断，解除颅高压和保护视力为目的，不必要求全切，而放疗应作为主要的治疗手段，术后充分合理的放疗，能使肿瘤明显缩小，甚至消失。

蓖麻蚕性细胞发育过程染色体的银染观察

用银染法观察了蓖麻蚕生殖细胞的染色体。结果表明：有丝分裂中期染色体上无特异的ＮＯＲｓ；精母细胞减数分裂偶线期和粗线期核仁逐步弥散，粗线期之后有一个染色体分散为染色质，核仁弥散于其中形成嗜银的二价体的第二收缩期和混乱期；卵母细胞的相应时期，有一个核仁扩增的过程。依据染色体嗜银性的强弱，探讨了前期Ⅰ，中期Ⅰ以及有丝分裂中期染色体的ｒＤＮＡ转录活性。

Effects of Oestrogen on Ischemia-induced Neurogenesis in the Dentate Gyrus of Rats

To study the effects of oestrogcn on ischemia-induced neurogenesis in the hippocampal dentate gyms, thirty-two adult male rats were randomly divided into four groups： the control surgery group with eestrogen administration （SE）, the control surgery group with normal saline administration （SN）, the middle cerebral artery occlusion （MCAO） group with oestrogen administration （ME） and the MCAO group with normal saline administration （MN）. The MCAO rats were occluded for 90 rain by an intraluminal filament and then recirculated. After 1, 3, 12, 24 and 28 h of MCAO, the rats of the four groups were killed to investigate the infarct volume, apoptosis and neurogenesis. The cerebral infarct volume in the ME group was significantly smaller than that of the MN group （P 〈 0.05）. No significant cell loss was seen in the dentate gyms. Cerebral ischemia led to increased neurogenosis, which is independent of cell death in the ipsilateral dentate gyrus（P 〈 0.05）. BrdU-pesitive cells in the ipsilateral dentate gyms of the ME group were significantly increased when compared with those of the MN group（P 〈 0.05）. In the SE group, BrdU-positive cells in both the ipsilateral and contralateral dentate gyms, were increased when compared with those of the SN group （ P 〈 0.05 ）. We concluded that ocstregen plays an important role in neurogenesis, which is independent of ischemia-induced by MCAO in the hippocampal dentate gyms of rats.

Programmed Cell Death During Secondary Xylem Differentiation in Eucommia ulmoides

Programmed cell death (PCD) during secondary xylem differentiation in Eucommia ulmoides Oliv. was examined using electron microscopy and by investigation of DNA fragmentation and degradation of caspase-like proteases (CLPs). DNA ladders were detected in developing secondary xylem by gel electrophoresis. DNA fragmentation was further confirmed by using the TdT-mediated dUTP nick-end labeling (TUNEL) method. Western blotting analysis showed that CLPs (caspase-8- and caspase-3-like proteases) and PARP (poly (ADP-ribose) polymerase) were degraded during secondary xylem differentiation. The results thus indicated that secondary xylem differentiation in E ulmoides was a typical process of PCD and the degradation of CLPs might be a constitutive PCD event during secondary xylem differentiation.

Biological Characteristics of Endothelial Progenitor Cell and Its Influence on Angiogenesis Improvement

Endothelial progenitor cell （EPC） is a term that refers to multiple cell types that play roles in the regeneration of the endothelial lining of blood vessels. The EPCs in bone marrow will participate in the internal circulation in a body sub- jected to the stimulation by external factors such as injury, ischemia or drug. EPCs regulate the angiogenic switch via paracrine secretion of proangiogenic growth factors and by direct luminal incorporation into sprouting nascent vessels. Therefore, this paper reviews the sources, isolation and culture of EPCs, the factors influencing the proliferation and activity of EPCs, and the roles of EPCs in angiogenesis.

Morphological Changes in Nucellar Cells Undergoing Programmed Cell Death (PCD) During Pollen Chamber Formation in Ginkgo biloba

Programmed cell death (PCD) of the nucellar cells at the micropylar end is involved in pollen chamber morphogenesis in Ginkgo biloba L. A development-course observation of the morphological changes in the nucellar cells undergoing PCD to form pollen chamber was performed. During the PCD, the nucellar cells degraded their cellular components through an orderly progression. Through the vactiolation, the cytosol was engulfed by the enlarging vacuole, leaving out various organelles, which remained morphologically integrated. As the vacuolation continued, the vacuole collapsed with the breakage of the tonoplast and the cytosol disappeared completely. Organelles were subsequently destroyed. Ultimately, nucellar cells digested away all of their cytoplasm, leaving with cell walls. They became collapsed as the nucellus developed. Intracellular membranes were strikingly changed, playing a role in leading to cell death. Some of these noticeable changes were the appearance of multivesicular body, multicycle-like membranes, membrane-bounded bodies containing some organelles, tonoplast rupture and numerous vesicles. The dehiscence of the apical epidermis, resulting in the opening, appeared to have followed two different pathways with one involving a specific epidermal cell autolysis and the other by detachment from middle lamella of two neighboring epidermal cells without cell autolysis. The specific epidermal cells had been dead prior to the dehiscence of the apical epidermis, which marked the sites of the dehiscence followed. In view of the changes in the cellular morphology, a process of nucellar cell PCD in the course of the pollen chamber formation was demonstrated.

Gastric carcinogenesis

Gastric cancer is the second most common cancer worldwide and the second most common cause of cancer-related deaths. Despite complete resection of gastric cancer and lymph node dissection, as well as improvements in chemotherapy and radiotherapy, there are still 700 000 gastric cancer-related deaths per year worldwide and more than 80% of patients with advanced gastric cancer die of the disease or recurrent disease within 1 year after diagnosis. None of the treatment modalities we have been applying today can influence the overall survival rates:at present, the overall 5-year relative survival rate for gastric cancer is about 28%. Cellular metaplasia due to chronic inflammation, injury and repair are the most documented processes for neoplasia. It appears that chronic inflammation stimulates tumor development and plays a critical role in initiating, sustaining and advancing tumor growth. It is also evident that not all inflammation is tumorigenic. Additional mutations can be acquired, and this leads to the cancer cell gaining a further growth advantage and acquiring a more malignant phenotype. Intestinalization of gastric units, which is called "intestinal metaplasia"; phenotypic antralization of fundic units, which is called "spasmolytic polypeptide-expressing metaplasia"; and the development directly from the stem/progenitor cellzone are three pathways that have been described for gastric carcinogenesis. Also, an important factor for the development of gastrointestinal cancers is peritumoral stroma. However, the initiating cellular event in gastric metaplasia is still controversial. Understanding gastric carcinogenesis and its precursor lesions has been under intense investigation, and our paper attempts to highlight recent progress in this field of cancer research.

Activation-induced cell death in B lymphocytes

Upon encountering the antigen (Ag), the immune system can either develop a specific immune response or enter a specific state of unresponsiveness, tolerance. The response of B cells to their specific Ag can be activation and proliferation, leading to the immune response, or anergy and activation-induced cell death (AICD), leading to tolerance. AICD in B lymphocytes is a highly regulated event initiated by crosslinking of the B cell receptor (BCR). BCR engagement initiates several signaling events such as activation of PLCr, Ras, and PI3K, which generally speaking, lead to survival. However, in the absence of survival signals (CD40 or IL-4R engagement), BCR crosslinking can also promote apoptotic signal transduction pathways such as activation of effector caspases, expression of pro-apoptotic genes, and inhibition of pro-survival genes. The complex interplay between survival and death signals determines the B cell fate and, consequently, the immune response.

BASIC FIBROBLAST GROWTH FACTOR GENE TRANSFECTION TO ENHANCE THE REPAIR OF AVASCULAR NECROSIS OFTHE FEMORAL HEAD

Objective To explore a new method for the therapy of avascular necrosis of the femoral head. Method The recombinant plasmid pCD-rbFGF was mixed with collagen and was implanted in the necrotic femoral head. Expression of basic fibroblast growth factor (bFGF) was examined by RT-PCR and immunohistochemical method. Re-pair of the femoral head was observed by histological and histomorphometric analysis. Result Expression of bFGF was detected in the femoral head transfected with bFGF gene, indicating significant increase of angiogenesis 2 weeks after gene transfection and increased new bone formation 8 weeks after gene transfection on histom-orphometric analysis (P< 0.01). Conclusion Transfection of bFGF gene enhances bone tissue angiogenesis. Repair in osteonecrosis would be accelerated accordingly.

Reduced Expression of Programmed Cell Death 5 Protein in Tissue of Human Prostate Cancer

Objective To investigate the expression of programmed cell death 5 （PDCD5） in tissues of normal human prostate （NP）, benign prostatic hyperplasia （BPH）, and prostate cancer （PCa） in order to assess the clinical role of PDCD5 in PCa. Methods PDCD5 expression was determined by EnVision immunohistochemical staining in forma-lin-fixed and paraffin-embedded specimens obtained from 12 subjects with NP, 22 with BPH, and 22 with PCa. In addition, PCa cases were classified as low/middle-risk （Gleason sumS7） and high-risk （Gleason sum〉7） on the basis of Gleason grade. Positive expression rates and intensity of PDCD5 protein were observed under light microscope and analyzed with computer imaging technique. Expression of PDCD5 was compared among different prostatic tissues. Results The expression of PDCD5 was significantly lower in tissue of PCa than in tissues of NP and BPH （P〈0.01）. However, there was no significant difference in PDCD5 expression between tissues of NP and BPH. In addition, the expression of PDCD5 was further downregulated with the increase of Gleason sum in PCa. Conclusions By downregulating apoptosis, low PDCD5 expression may play an important role in the occurrence and development of PCa. PDCD5 is supposed to have a potential clinical value to be a new predictor of progression and target of gene therapy in PCa.

Theoretical Investigation on QSAR of(2-Methyl-3-biphenylyl)methanol Analogs as PD-L1 Inhibitor

Cancer is one of the most serious issues in human life.Blocking programmed cell death protein 1 and programmed death ligand-1(PD-L1)pathway is one of the great innovations in the last few years,a few numbers of inhibitors can be able to block it.(2-Methyl-3-biphenylyl)methanol derivative is one of them.Here,the quantitative structure-activity relationship(QSAR)established twenty(2-methyl-3-biphenylyl)methanol derivatives as the programmed death ligand-1 inhibitors.Density functional theory at the B3LPY/6-31+G(d,p)level was employed to study the chemical structure and properties of the chosen compounds.Highest occupied molecular orbital energy EHOMO,lowest unoccupied molecular orbital energy ELUMO,total energy ET,dipole moment DM,absolute hardnessη,absolute electronegativityχ,softness S,electrophilicityω,energy gap?E,etc.,were observed and determined.Principal component analysis(PCA),multiple linear regression(MLR)and multiple nonlinear regression(MNLR)analysis were carried out to establish the QSAR.The proposed quantitative models and interpreted outcomes of the compounds were based on statistical analysis.Statistical results of MLR and MNLR exhibited the coefficient R^2 was 0.661 and 0.758,respectively.Leave-one-out cross-validation,r_m^2 metric,r_m^2 test,and"Golbraikh&Tropsha’s criteria"analyses were applied for the validation of MLR and MNLR,which indicate two models are statistically significant and well stable with data variation in the external validation towards PD-L1.The obtained results showed that the MNLR model predicts the bioactivity more accurately than MLR,and it may be helpful and supporting for evaluation of the biological activity of PD-L1 inhibitors.

Investigation into the hemolytic activity of tentacle venom from jellyfish Cyanea nozakii Kishinouye

Cyanea nozakii Kishinouye （C. nozakii）, a giant cnidarian of the class Scyphomedusae, order Semaeostomeae and family Cyaneidae, is widely distributed in the East China Sea, the Yellow Sea and the Bohai Sea, and is abundant from late summer to early autumn. Venom produced by C. nozakii during mass agglomerations can contaminate seawater resulting in death of the halobios and seriously damage commercial fisheries. Swimmers and fishermen commonly suffer painful stings from this j ellyfish, resulting in local edema, tingling, breathing difficulties, depressed blood pressure and even death. Such effects arise from the complex mixture of biologically active molecules that make up jellyfish venom. In the present study, the hemolytic activity of venom from tentacles of C. nozakii and factors affecting its activity were assayed. The HUso （defined as the amount of protein required to lyse 50% of erythrocytes） of the venom against dove and chicken erythrocytes was 34 and 59 gg/mL, respectively. Carboxylmethyl chitosan and glycerol could increase hemolytic activity at concentrations greater than 0.06% and 0.2 mol/L, respectively.

p53 INDEPENDENT G_1 ARREST AND APOPTOSIS INDUCED BY ADRIAMYCIN

The biological activity of adriamycin was investigated in human breast carcinoma (HBC) cells. Adri-amycin inhibited the growth of a number of HBC cell lines and induced G1 arrest followed by apoptosis. In MCF-7 cells that harbor wild-type p53, adriamycin-induced G1 arrest and apoptosis was accompanied by p53-independent regulation of WAF1/CIP1 as well as bax mRNA levels. In MDA-MB-231 cells which possess a mutant p53, adriamycin-induced G1 arrest and apoptosis was also associated with a cpncomitant up-regulation of WAF1/CIP1 mRNA while these cells did not express bax or bcl-2 messages. Thus, adriamycin induces G1 arrest and apoptosis via a unique pathway which appears to involve activation of downstream effectors of p53-independent manner.

Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart

Cannabinoid receptor type 2(CB2)activation is recently reported to promote proliferation of some types of resident stem cells(e.g.,hematopoietic stem/progenitor cell or neural progenitor cell).Resident cardiac progenitor cell(CPC)activation and proliferation are crucial for endogenous cardiac regeneration and cardiac repair after myocardial infarction(MI).This study aims to explore the role and possible mechanisms of CB2receptor activation in enhancing myocardial repair.Our results revealed that CB2receptor agonist AM1241 can significantly increase CPCs by c-kit and Runx1 staining in ischemic myocardium as well as improve cardiomyocyte proliferation.AM1241 also decreased serum levels of MDA,TNF-αand IL-6 after MI.In addition,AM1241 can ameliorate left ventricular ejection fraction and fractional shortening,and reduce fibrosis.Moreover,AM1241 treatment markedly increased p-Akt and HO-1 expression,and promoted Nrf-2 nuclear translocation.However,PI3K inhibitor wortmannin eliminated these cardioprotective roles of AM1241.In conclusion,AM1241 could induce myocardial regeneration and improve cardiac function,which might be associated with PI3K/Akt/Nrf2 signaling pathway activation.Our findings may provide a promising strategy for cardiac endogenous regeneration after MI.

Nanomedicine enables autophagy-enhanced cancer-cell ferroptosis

Ferroptosis and autophagy, playing significant roles in tumor treatment, are two typical forms of the programmed cell death. However, the rational combination of ferroptosis and autophagy for synergistic tumor therapy is still highly challenging. Herein, we report on an intriguing nanomedicine strategy for achieving autophagy-enhanced ferroptosis on efficiently combating cancer, which was based on the construction of trehalose-loaded mSiO_(2)@MnO_(x)-mPEG(Tre MMM) nanoparticles with satisfactory biocompatibility. The nanoparticles are endowed with high glutathione(GSH) consumption efficiency, thereby inducing cancer-cell ferroptosis via inactivating glutathione peroxidases 4(GPX4). Subsequently, the Tre MMM degradation due to the GSH depletion and p H sensitivity contributed to the trehalose release for inducing autophagy, promoting/enhancing ferroptosis by NCOA4-mediated degradation of ferritin.A substantial in vitro and in vivo antitumor effect was achieved by such an intriguing autophagyenhanced ferroptosis. Therefore, the rational combination of GSH-consumption-induced ferroptosis and trehalose-induced autophagy by nanomedicine design provides an alternative but effective strategy for tumor treatment.