Ovarian cancer is a common malignant tumor in women, and 70 % of ovarian cancer patients are diagnosed at an advanced stage. Drug chemotherapy is an important method for treating ovarian cancer, but recurrence and chemotherapy resistance often lead to treatment failure. In this study, we screened 10 extracts of Tripterygium wilfordii, a traditional Chinese herb, and found that triptonide had potent anti-ovarian cancer activity and an IC50 of only 3.803 nM against A2780 cell lines. In addition, we determined that triptonide had a better antitumor effect on A2780 cell lines than platinum chemotherapeutic agents in vitro and that triptonide had no significant side effects in vivo. We found that triptonide induced apoptosis in ovarian cancer cells through activation of the p38/p53 pathway and it also induced cell cycle arrest at the S phase. In addition, we demonstrated that triptonide could activate lethal autophagy, which led to growth inhibition and cell death in ovarian cancer cells, resulting in an anti-ovarian cancer effect. Triptonide exerts its anti-ovarian cancer effect through activation of the p38/p53 pathway and induction of autophagy to promote apoptosis, which provides a new candidate drug and strategy for the treatment of ovarian cancer.

肺癌肉瘤是肺肉瘤样癌的一种组织学亚型，发病率低，具有高度侵袭性，易于复发和转移。该文报道1例53岁女性原发性肺癌肉瘤病例，为肺腺癌和未分化肉瘤两种成分混合。分子检测显示间变性淋巴瘤激酶（ALK）基因重排。总结其临床病理学特征、组织形态和免疫表型、诊断与鉴别诊断，以及分子生物学特征，以提高对本病的认识。.

Astaxanthin (Ast) is an effective neuroprotective and antioxidant compound used to treat Alzheimer's disease (AD); however, the underlying in vivo molecular mechanisms remain unknown. In this study, we report that Ast can activate the mammalian target of rapamycin (mTOR) pathway in the 8-month-old APP/PS1 transgenic mouse model of AD. Our results suggest that Ast could ameliorate the cognitive defects in APP/PS1 mice by activating the mTOR pathway. Moreover, mTOR activation perturbed the mitochondrial dynamics, increased the synaptic plasticity after 21 days of treatment with Ast (10 mg/kg/day), and increased the expression of Aβ-degrading enzymes, mitochondrial fusion, and synapse-associated proteins and decreased the expression of mitochondrial fission proteins. Intraperitoneal injection of the mTOR inhibitor, rapamycin, abolished the effects of Ast. In conclusion, Ast activates the mTOR pathway, which is necessary for mitochondrial dynamics and synaptic plasticity, leading to improved learning and memory. Our results support the use of Ast for the treatment of cognitive deficits. Graphical abstract In summary, Ast ameliorates cognitive deficits via facilitating the mTOR-dependent mitochondrial dynamics and synaptic damage, and reducing Aβ accumulation. This model supports the use of Ast for the treatment of cognitive deficits.

Oxidative stress is a potential pathological mechanism of Alzheimer’s disease (AD). Berberine (BBR) can improve antioxidative capacity and inhibit Aβ protein aggregation and tau protein hyperphosphorylation in AD, and stem cell therapy is also increasingly recognized as a therapy for AD. Bone marrow mesenchymal stem cells (BMSCs) have many advantages, as they exhibit antioxidant and anti-inflammatory activity and secrete a variety of neurotrophic factors, and play important roles in neurodegenerative disease treatment. In this study, we investigated the antioxidant effects of secretions from BMSCs pretreated with BBR on tert -butyl hydroperoxide ( t -BHP)–damaged neurons. We demonstrated that BBR can enhance BMSC viability and the secretion of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), both of which are vital neurotrophic factors that maintain neuronal growth. Moreover, conditioned medium from BBR-treated BMSCs (BBR-BMSC-CM) reduced reactive oxygen species (ROS) production, attenuated a decrease in the mitochondrial membrane potential, and ameliorated neuronal apoptosis by decreasing levels of the apoptotic proteins Bax/Bcl-2, cytochrome c, and cleaved caspase-3/caspase-3. In addition, increased synaptophysin (SYP) and postsynaptic density protein 95 (PSD95) levels indicated that neuronal synaptic function was restored. Further study revealed that BBR-BMSC-CM activated the antioxidant proteins Keap1, Nrf2, and HO-1. In conclusion, our results showed that BBR-BMSC-CM attenuated apoptosis and oxidative damage in neurons by activating the Keap1-Nrf2-HO-1 signaling pathway. Taken together, these results also suggest BBR as a drug to stimulate the secretion of nutritional cytokines with the potential to treat AD.

Oxidative stress is a key factor of and closely implicated in the pathogenesis of Alzheimer’s disease (AD). We herein used tert-butyl hydroperoxide (t-BHP) to induce oxidative stress and mimic oxidative neurotoxicity in vitro. Lycopene is a natural antioxidant that has a strong ability to eliminate free radicals and shows effective protection in some neurodegenerative disease models. However, the effect of lycopene on t-BHP-induced neuronal damage in primary mouse neurons is unknown. This study aimed to investigate the effects of lycopene on t-BHP-induced neuronal damage and the related mechanisms. We found that lycopene pretreatment effectively enhanced the cell viability, improved the neuron morphology, increased the GSH/GSSG level, restored the mitochondrial membrane potential (ΔΨm) and decreased reactive oxygen species generation. Furthermore, lycopene reduced the ratios of Bax:Bcl-2 and cleaved caspase-3:caspase-3 and the level of cytochrome C, increased the levels of synaptophysin (SYP) and postsynaptic density 95 (PSD95) and activated the PI3K/Akt pathway. In conclusion, lycopene attenuated oxidative stress and reduced t-BHP-induced cell apoptosis, and the mechanism is likely related to activation of the PI3K/Akt pathway. Therefore, lycopene is a potential agent for preventing oxidative stress-mediated AD.

A promising intervention for Alzheimer's disease (AD) would ideally target key pathological factors that are involved in AD pathogenesis. Soluble factors produced by engrafted mesenchymal stem cells (MSCs) mediate potential therapeutic effects in AD. However, these therapeutic benefits are largely hampered by the limited paracrine capacity of MSCs. In this study, we used adenovirus-mediated gene transduction of bone marrow MSCs to deliver exogenous proteins into the brain of APPswe/PSEN1dE9 (APP/PS1) mice in the early stage of impairment. We observed that engrafted MSCs carrying exogenous (C-X3-C motif) ligand 1 (CX3CL1) alone reduced the production of the inflammatory cytokine TNF-ɑ and improved synapse-related protein expression but not cognitive function. Transplantation of MSCs carrying CX3CL1 and Wnt3a (CX3CL1-Wnt3a-MSC) significantly attenuated the learning and memory impairment when compared with a control group. The improvement of neurobehavioral functions in APP/PS1 mice treated with CX3CL1-Wnt3a-MSC was related to the inhibition of microglial neurotoxicity and promotion of hippocampal neurogenesis. Transplantation of CX3CL1-Wnt3a-MSC also regulated phosphoinositide 3-kinase/activated protein kinase B (PI3K/AKT) signaling to inhibit the activity of glycogen synthase kinase 3 beta (GSK3β). Taken together, these results indicate that the delivery of exogenous proteins via MSCs can modulate microglial function and enhance neurogenesis, thereby providing new insights into AD intervention.

Neural stem cells (NSCs) hold great potential for the treatment of Alzheimer's disease (AD) through both cellular replacement and their secretion of trophic factors. Lycopene is a potent β-carotenoid antioxidant that has been shown to ameliorate oxidative damage in previous studies. However, it is unclear if lycopene can interact with NSCs to induce the secretion of growth factors, and whether pretreatment with lycopene will allow NSCs to secrete enough trophic factors to reduce oxidative damage to neurons. We pretreated cultured NSCs with lycopene, then applied the lycopene-treated-NSC-conditioned media (Ly-NSC-CM) to primary neuronal cultures exposed to tert-butyl hydroperoxide (t-BHP) to induce oxidative damage. We found that lycopene promoted the secretion of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF) from NSCs. In addition, Ly-NSC-CM attenuated oxidative stress and reduced t-BHP-induced cell apoptosis. We found an antiapoptotic effect related to inhibited expression of Bax/Bcl-2, cytochrome C, and cleaved caspase-3. Moreover, Ly-NSC-CM increased the levels of synaptic proteins, including synaptophysin (SYP) and postsynaptic density 95 (PSD-95), and activated the PI3K/Akt pathway in cultured neurons. Collectively, these data indicate that Ly-NSC-CM could protect neurons from t-BHP-induced oxidative damage.

AIM:To investigate the protective effect of lycopene on primary mouse cerebrocortical neurons ex -posed to tert-butyl hydroperoxide ( t-BHP) and its mechanisms of in vitro.METHODS:Primary cerebrocortical neurons of newborn C57 mice were extracted and divided into normal group , t-BHP group, lycopene +t-BHP group and lycopene group.The neuronal damage was induced by t-BHP exposure for 24 h, and the cell viability was examined by MTT assay . ROS content was measured by flow cytometry , and the protein levels of Bax , Bcl-2, caspase-3, cleaved caspase-3 and cyto-chrome C were examined by Western blot .RESULTS:The primary mouse cortical neurons expressed MAP-2 protein.Ly-copene at concentration of 4μmol/L reversed the decrease in cell viability .Flow cytometry revealed that lycopene treatment attenuated ROS content under the condition of t-BHP exposure.In addition, the protein level of Bcl-2 was increased, and the expression of Bax , cleaved caspase-3 and cytochrome-C was suppressed in lycopene +t-BHP group.CONCLUSION:The protective effect of lycopene on cortical neurons with t-BHP-induced injury may be involved in the mechanism of neuro-nal antioxidative response by down-regulating caspase-3 and Bax/Bcl-2 through the mitochondrial apoptotic pathway .

AIM:To investigate the effect of bone marrow mesenchymal stem cell(BMSC) transplantation on learning and memory abilities and pathological changes of Alzheimer disease (AD) mice and the molecular mechanisms. METHODS:C57/BL6 wild-type (WT) and transgenic(Tg) mice were randomly divided into 4 groups:WT/PBS group, WT/BMSCs group,Tg/PBS group and Tg/BMSCs group. The mice were administered with PBS or BMSCs via intracere-broventricular injection. Spatial learning and memory abilities of the mice were evaluated by Morris water maze test on the 3rd day after surgery. Real-time PCR was applied to detect the mRNA expression of CX3C chemokine ligand 1 (CX3CL1),CX3C chemokine receptor 1 (CX3CR1), IL-1β, TNF-α, Nurr1, YM1, insulin-degrading enzyme (IDE) and matrix metalloproteinase 9(MMP9). The protein levels of CX3CL1 and Aβ42 were measured by ELISA. Western blot was used to detect the protein expression of postsynaptic density protein 95 (PSD95) and synaptophysin (SYP). RE-SULTS:The transplanted BMSCs were observed near the hippocampus of APP/PS1 mice on the 10th postoperative day. The escape latency of the mice in Tg/PBS group was significantly longer than that in the WT/PBS mice(P<0.05). Com-pared with Tg/PBS group,the escape latency of Tg/BMSCs group was significantly shorter (P<0.05), and the mRNA and protein levels of CX3CL1 in Tg/BMSCs group were significantly higher than those in Tg/PBS group (P<0.01). The results of immunohistofluorescence staining showed that BMSC transplantation promoted the activation of microglia in the brain of WT and Tg mice. The mRNA expression of YM1 was up-regulated in WT/BMSCs group and Tg/BMSCs group (P<0.05). Compared with WT/PBS mice, the mRNA expression of TNF-α in the cortex and hippocampus of Tg/PBS group was significantly increased (P<0.05),and the mRNA expression of Nurr1 in the cortex was significantly decreased (P<0.01). Meanwhile,the mRNA expression of TNF-α in the cortex of Tg/BMSCs mice was decreased(P<0.01) and the mRNA expression of CX3CR1 and Nurr1 was up-regulated compared with Tg/PBS group (P<0.05). The results of Western blot showed that the protein levels of PSD95,p85,p110 and p-Akt in Tg/BMSCs group were significantly higher than those in Tg/PBS group (P<0.05). Finally, BMSC transplantation reduced the protein level of Aβ42 in APP/PS1 mice(P<0.05), and increased the mRNA expression of IDE and MMP9 in the hippocampus (P <0.05). CONCLU-SION:BMSC transplantation modulates neuroinflammatory responses and promotes neuroprotective factor and synaptic pro-tein expression,thus improving the learning and memory abilities in the APP/PS1 mice,which may be achieved by up-reg-ulating the expression of CX3CL1.

目的:观察叶黄素(lutein)对叔丁基过氧化氢(t-BHP)处理的视网膜神经节细胞(RGC-5细胞系)的保护效应并探讨其作用机制.方法:用免疫荧光染色检测视网膜神经节特异性蛋白Bm-3和神经微管结合蛋白MAP-2的表达来鉴定RGC-5细胞;将RGC-5细胞随机分为对照组、t-BHP处理组、t-BHP和lutein共同处理组、lutein处理组,培养24 h,MTT实验检测细胞活力;Annexin V-FITC/PI双染流式细胞术检测细胞凋亡;免疫细胞化学技术检测easpase-3蛋白的活化情况;Western blot检测Bcl-2/Bax、cleaved caspase-3、JNK和c-Jun蛋白的变化.结果:MTT实验和流式细胞检测结果显示,lutein能提高t-BHP处理的RGC-5细胞的活力,并降低t-BHP诱导的RGC-5细胞凋亡;免疫荧光结果显示lutein能抑制t-BHP诱导的caspase-3的活化;与对照组比较,t-BHP处理后RGC-5细胞抗凋亡蛋白Bcl-2表达下调(P＜0.05),Bax/Bcl-2比率升高,cleaved caspase-3表达上调(P＜0.05),JNK和c-Jun蛋白的磷酸化水平增加(P＜0.05),t-BHP的上述作用可被lutein部分逆转.结论:Lutein能够降低t-BHP诱导的RGC-5细胞凋亡,其机制与其上调Bcl-2的表达、抑制caspase-3的活化并降低JNK和c-Jun蛋白的磷酸化有关.

Objective To investigate the genomic amplification of human telomerase gene ( hTERC ) in paraffin -embedded tissues of cervical intraepithelial neoplasia (CIN) and cervical cancer (CC) by fluorescence in situ hybridization (FISH) in order to&nbsp;evaluate its clinical significance in cervical cancer screening .Methods The genomic amplification of hTERC gene in 166 cases of cervical paraffin-embedded tissues were delected by FISH collected The First Affiliated Hospital of Jinan University from October 2008 to February 2011.According to the histology biopsy , 166 cases divided into the control group (18 cases of normal , chronic cervicitis or metaplasia of squamous epithelium )and the study groups (166 cases), including CINⅠ(30 cases), CINⅠ-Ⅱ(28 cases), CINⅡ(35 cases), CINⅢ(35 cases) and cervical cancer (20 cases), of which 15 cases of initial treatment (11 cases of squamous cell carcinoma, 3 cases adenosquamous carcinoma , and 1 case adenocarcinoma ) and 5 cases of relapse after treatment .To detect the genomic amplification of hTERC gene in the paraffin tissues of each group by FISH , and compared with the results of cervical cytology , HPV-DNA detection, colposcopy.Results (1)The genomic amplification rate of hTERC gene in the control group , CIN Ⅰ, CINⅠ-Ⅱ, CIN Ⅱ, CINⅢand cervical cancer group were 5.6%, 10.0%, 32.1%, 65.7%, 88.6% and 95.0% respectively .The difference of hTERC genomic amplification between control group , CINⅠand CINⅠ -Ⅱ, CINⅡ, CINⅢ, cervical cancer was statistically significant (P<0.05).The genomic amplification rate of hTERC increased with the degree of cervical lesion gradually increased (χ2 =12.270, P<0.05).(2) The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood ratio , negative likelihood ratio and Youden index of the genomic amplification of hTERC in the paraffin specimens for predicting high -grade cervical lesions were 81.1%, 79.3%, 80.4%, 85.9%, 73.0%, 3.92, 0.24 and 0.60 respectively. Conclusion The amplification of hTERC in the paraffin -embedded tissues have high positive rate for predicting high -grade cervical lesions.

目的：观察叶黄素对视网膜神经节细胞系（ RGC－5）的保护作用，并对其机制进行初步探讨。方法：将RGC－5细胞随机分为：对照组、t－BHP组、t－BHP和叶黄素共同作用组、叶黄素组，培养24 h，MTT检测细胞活力；Annexin V－FITC／PI 双染流式细胞仪检测细胞凋亡率；免疫细胞化学法检测caspase－3蛋白的活化情况；Western blot检测Bcl－2／Bax、cleaved caspase－3、JNK和c－Jun蛋白的变化。结果：MTT法和流式细胞检测结果显示叶黄素可对抗t－BHP诱导的RGC－5细胞凋亡；免疫荧光结果显示叶黄素可减少t－BHP诱导的caspase－3的活化；Western blot结果显示t－BHP处理后RGC－5细胞抗凋亡蛋白Bcl－2表达下调，促凋亡蛋白Bax和cleaved caspase－3表达上调，JNK和c－Jun蛋白的磷酸化水平增加，叶黄素能部分逆转上述结果。结论：叶黄素能够对抗t－BHP诱导的RGC－5细胞凋亡而显示其保护作用，其机制是抑制Bax／Bcl－2表达及caspase－3蛋白活化，并降低JNK和c－Jun蛋白的磷酸化。

The aim of this study is to investigate whether partial liver irradiation promotes hepatic regeneration in rat. Left-half liver of rat was irradiated to 10 Gy, and the Right-half to 0, 5, 10 and 15 Gy, respectively. Then, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels were evaluated on 0 day, 15-day, 30-day, 45-day and 60-day after liver irradiation. Next, the serum HGF, NF-κB and TGF-β1 levels were also analyzed on 60-day after liver irradiation. Lastly, the cyclinD1 protein expression was appraised by western blots on 60-day after liver irradiation. ALT, AST and ALP levels were reduced compared with that of controls. The serum HGF, NF-κB and TGF-β1 levels, and the cyclinD1 protein expression in liver irradiation group were increased compared with that of controls group. However, hepatic regeneration of higher dose-irradiated cirrhotic liver was triggered a more enhanced regeneration, compared with that of higher doses group. In summary, these results suggest that different doses of partial liver irradiation promotes hepatic regeneration in rat.

Objective To study the expression and clinical significance of up-regulated gene 11 (URG11) in prostate cancer.Methods Sixty-eight patients diagnosed as prostate cancer from June 2010 to June 2013 at the First Affliated Hospital of Ji' nan University were retrospectively.The expression of URG11 was detected by immunohistochemistry in prostate cancer and benign prostatic hyperplasia tissues.Results The positive expression rate of UGR11 in prostate cancer and benign prostatic hyperplasia tissues was 70.6％ and 21.6％ respectively (x2 =34.32,P ＜0.01).The expression of UGR11 in prostate cancer was significantly correlated with the pathological grading system (Gleason grading system) and TNM staging (r =0.354,0.740,P ＜ 0.05),but not with age (P ＞ 0.05).Conclusion The increased expression of UGR1 1 in prostate cancer is closely correlated with pathogenesis of prostate cancer.

乳腺神经内分泌癌是一种十分少见的乳腺肿瘤， Up-alakalin等［1］统计其发病率约占所有乳腺癌总数的1％；由于报道少、病例不多，目前尚缺乏规范化的诊治指南。乳腺神经内分泌癌分为原发性癌及转移癌2种。原发性癌的临床表现缺乏特异性，往往通过病理确诊，国内外虽有文献报道该病的各种发病特点，但未见有合并性激素改变者。本文结合暨南大学附属第一医院1例合并有高泌乳素血症的原发性神经内分泌癌病例进行文献复习，探讨该病的诊断及其与高泌乳素血症的相关性供临床参考。

目的：研究《傅青主女科》升带汤对子宫内膜异位症模型大鼠的异位内膜的病理影响。方法：自体移植法制备子宫内膜异位症大鼠模型，随机分为模型组、治疗组。模型组每日给予2m L生理盐水灌胃，中药组每日给予升带汤10m L／kg ，连续给药20d。处死大鼠，剥取在位及异位子宫内膜组织，石蜡病理切片，HE染色观察。结果：模型组大鼠在位、异位内膜比较。当大鼠在位内膜处于增生晚期时，其异位内膜组织处于增生早期状态。治疗组大鼠在位、异位内膜比较。大鼠在位子宫内膜处于分泌期时。其异位内膜组织亦处于分泌期，间质部分蜕膜样变。结论：子宫内膜异位症模型大鼠异位与在位内膜组织存在不同步发育现象。升带汤有促使大鼠异位内膜组织蜕膜样变的作用。

Background: Glioma is the most common brain malignancy with poor prognosis. The current treatments for gliomas are mainly based on surgery, chemotherapy, and radiotherapy, which exhibit limited efficacy. Photodynamic therapy (PDT) using photosensitizers has been applied to glioma therapy. However, different photosensitizers usually lead to different therapeutic effects and adverse reactions.Objective: This study investigates the anti-tumor effect of photosensitizer ZnPcS4-BSA in xenograft glioma tumors.Methods: The xenograft glioma tumor model was established by inoculating nude mice with U251 cells. Tumor growth was evaluated by tumor volume, weight, and inhibition rate. Cell apoptosis was evaluated using TUNEL staining. Vascular endothelial growth factor (VEGF) expression and microvessel density were measured by immunohistochemistry.Results: Significant decreases in tumor volume and weight as well as significant increases in tumor inhibition rate, cell apoptosis, VEGF expression, and microvessel density were observed in mice in the low- and high-dose PDT groups compared to the control, irradiation alone, and photosensitizer alone groups. No significant difference in cytotoxicity was observed between control group and photosensitizer alone group. Photosensitizer ZnPcS4-BSA significantly inhibited xenograft glioma tumor growth through induction of apoptosis.Conclusion: PDT using ZnPcS4-BSA may be effective for the therapy of gliomas.

目的 探讨新型光敏剂四磺酸酞菁锌与牛血清白蛋白的配合物(ZnPcS4-BSA)介导的光动力疗法(PDT)对胶质瘤的体内光动力杀伤效应,并分析其杀伤机制.方法 建立裸鼠胶质瘤模型,将30只荷瘤裸鼠随机分为5组:荷瘤对照组、单纯光照组、单纯光敏剂组、低剂量PDT组和高剂量PDT组,经不同处理后处死裸鼠,切除肿瘤,比较各组抑瘤率、血管内皮生长因子(VEGF)表达水平、微血管密度(MVD)以及凋亡指数.结果 抑瘤率、VEGF水平、MVD、凋亡指数等指标检测显示,荷瘤对照组、单纯光照组、单纯光敏剂组3组间差异均无统计学意义,而高、低剂量PDT组均显著高于其它各组,且高剂量PDT组高于低剂量PDT组.结论 ZnPcS4-BSA对荷U251胶质瘤的裸鼠具有良好的光动力效能,其介导的PDT过程存在诱导肿瘤细胞凋亡这一机制,在肿瘤组织中VEGF表达在PDT后升高.