A bursal pentapeptide (BPP-I), a novel bursal-derived peptide, exhibits antiproliferation of tumor cell and immunomodulator activity

The bursa of Fabricius (BF) is the central humoral immune organ unique to birds. Here, we isolated a novel bursal pentapeptide I (BPP-I), LGPGP, from BF. BPP-I could play inhibition effect on MCF-7 but not on CEF or Vero cell proliferation in vitro, and enhance antitumor factor p53 protein expression. Also, BPP-I stimulated antibody production in a dose-dependent manner in hybridoma cell. Furthermore, BPP-I could induce various immune responses in mice immunization experiments, including increase antibody production and cytokines IL-4 and IFN-γ level, and induce T-cell immunophenotyping. These results suggest that BPP-I is a potential immunomodulator of antitumor and immunity. The study could provide some novel insights on the probable candidate reagent for the antitumor and immune improvement.     

Comparative Genome Analysis of Scutellaria baicalensis and Scutellaria barbata Reveals the Evolution of Active Flavonoid Biosynthesis

Scutellaria baicalensis (S. baicalensis) and Scutellaria barbata (S. barbata) are common medicinal plants of the Lamiaceae family. Both produce specific flavonoid compounds, including baicalein, scutellarein, norwogonin, and wogonin, as well as their glycosides, which exhibit antioxidant and antitumor activities. Here, we report chromosome-level genome assemblies of S. baicalensis and S. barbata with quantitative chromosomal variation (2n = 18 and 2n = 26, respectively). The divergence of S. baicalensis and S. barbata occurred far earlier than previously reported, and a whole-genome duplication (WGD) event was identified. The insertion of long terminal repeat elements after speciation might be responsible for the observed chromosomal expansion and rearrangement. Comparative genome analysis of the congeneric species revealed the species-specific evolution of chrysin and apigenin biosynthetic genes, such as the S. baicalensis-specific tandem duplication of genes encoding phenylalanine ammonia lyase and chalcone synthase, and the S. barbata-specific duplication of genes encoding 4-CoA ligase. In addition, the paralogous duplication, colinearity, and expression diversity of CYP82D subfamily members revealed the functional divergence of genes encoding flavone hydroxylase between S. baicalensis and S. barbata. Analyzing these Scutellaria genomes reveals the common and species-specific evolution of flavone biosynthetic genes. Thus, these findings would facilitate the development of molecular breeding and studies of biosynthesis and regulation of bioactive compounds.     

Claudin-7 suppresses the cytotoxicity of TRAIL-expressing mesenchymal stem cells in H460 human non-small cell lung cancer cells

Evidence suggests that the cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapeutics. Studies have also shown that claudin-7 (CLDN7) expression is variably dysregulated in various malignant neoplasms, with a role in lung cancer that has not been definitively decided. This work investigated the differential sensitivity of CLDN7-overexpressing human NSCLC H460 cells to TRAIL in vitro and in mouse xenografts, and explored the molecular mechanisms responsible for these effects. NCI-H460 cells were transfected or not with green fluorescent protein-tagged CLDN7. Each group was then exposed to mesenchymal stem cells (MSCs) or red fluorescent protein-tagged MSCs transduced with lentivirus expressing membrane-bound TRAIL. The effects and related mechanisms of these treatments were evaluated in vitro, and in vivo in murine xenografts. Our results indicate that TRAIL induced apoptosis in H460 cells in vitro, and in established xenograft tumors TRAIL was associated with a decrease in tumor size, tumor weight, and circulating tumor cells. CLDN7 was found to inhibit the MEK/ERK signaling pathway, leading to inhibition of death receptor 5 (TNFRSF10B). The cytotoxicity of TRAIL was confirmed in H460 cells and in vivo, and CLDN7 suppressed the cytotoxicity of TRAIL in H460 cells. Our results indicate that TRAIL may be a useful therapy to enhance apoptosis in CLDN7-negative lung cancer cells.     

Cyclin D1 G870A Polymorphism and Risk of Nasopharyngeal Carcinoma: A Case-Control Study and Meta-Analysis

Background

Cyclin D1 (CCND1) plays a key role in cell cycle regulation. It is a well-established human oncogene which is frequently amplified or overexpressed in cancers. The association between CCND1 G870A polymorphism and cancer risk has been widely assessed. However, a definitive conclusion between CCND1 G870A polymorphism and risk of nasopharyngeal carcinoma (NPC) remains elusive.

Methods

We firstly performed a hospital-based case-control study involving 165 NPC cases and 191 cancer-free controls in central-south China, and then conducted a meta-analysis with six case-control studies to evaluate the association between NPC risk and CCND1 G870A polymorphism.

Results

The case-control study found a significant association between CCND1 G870A polymorphism and NPC risk in various comparison models (AA vs. GG: OR = 2.300, 95% CI 1.089–4.857, p = 0.029; AG vs. GG: OR = 2.832, 95% CI 1.367–5.867, p = 0.005; AA/AG vs. GG: OR = 2.597, 95% CI 1.288–5.237, p = 0.008; AA vs. AG/GG: OR = 0.984, 95% CI 0.638–1.518, p = 0.944). Further meta-analysis showed that there was no significant association between CCND1 G870A polymorphism and NPC risk in overall analysis. In the stratified analysis by race, however, significant associations were only found in Caucasians (for the allele model A vs. G: OR = 0.75, 95% CI 0.59–0.97, p = 0.03; for the co-dominant model AA vs. GG: OR = 0.52, 95% CI 0.32–0.86, p = 0.01; for the dominant model AA/AG vs. GG: OR = 0.49, 95% CI 0.32–0.74, p<0.01; for the recessive model AA vs. AG/GG: OR = 0.90, 95% CI 0.61–1.34, p = 0.60).

Conclusions

A significant association between CCND1 G870A polymorphism and NPC risk was found in the central-southern Chinese population. The meta-analysis indicated that CCND1 G870A polymorphism may contribute to the development of NPC in Caucasians.     

Activation of Nuclear Factor Kappa B in the Hepatic Stellate Cells of Mice with Schistosomiasis Japonica

Schistosomiasis japonica is a serious tropical parasitic disease in humans, which causes inflammation and fibrosis of the liver. Hepatic stellate cells (HSCs) are known to play an important role in schistosome-induced fibrosis, but their role in schistosome-induced inflammation is still largely unknown. Here, we use a murine model of schistosomiasis japonica to investigate the role that nuclear factor kappa B (NF-κB), a critical mediator of inflammatory responses, plays in schistosome-induced inflammation. We revealed that NF-κB was significantly activated in HSCs at the early stage of infection, but not at later stages. We also show that the expression levels of several chemokines regulated by NF-κB signaling (Ccl2, Ccl3 and Ccl5) were similarly elevated at early infection. TLR4 signaling, one of the strongest known inducers of NF-κB activation, seemed not activated in HSCs post-infection. Importantly, we found that levels of miR-146 (a known negative regulator of NF-κB signaling) in HSCs opposed those of NF-κB signaling, elevating at later stage of infection. These results indicate that HSCs might play an important role in the progression of hepatic schistosomiasis japonica by linking liver inflammation to fibrosis via NF-κB signaling. Moreover, our work suggests that miR-146 appeared to regulate this process. These findings are significant and imply that manipulating the function of HSCs by targeting either NF-κB signaling or miR-146 expression may provide a novel method of treating hepatic schistosomiasis japonica.     

Anti-proliferative effects of evodiamine on human prostate cancer cell lines DU145 and PC3

Prostate carcinoma is one of the most common malignant tumors and has become a more common cancer in men. Previous studies demonstrated that evodiamine (EVO) exhibited anti-tumor activities on several cancers, but its effects on androgen-independent prostate cancer are unclear. In the present study, the action mechanisms of EVO on the growth of androgen-independent prostate cancer cells (DU145 and PC3 cells) were explored. EVO dramatically inhibited the growth and elevated cytotoxicity of DU145 and PC3 cells. The flow cytometric analysis of EVO-treated cells indicated a block of G2/M phase and an elevated level of DNA fragmentation. The G2/M arrest was accompanied by elevated Cdc2 kinase activity, an increase in expression of cyclin B1 and phosphorylated Cdc2 (Thr 161), and a decrease in expression of phosphorylated Cdc2 (Tyr 15), Myt-1, and interphase Cdc25C. TUNEL examination showed that EVO-induced apoptosis was observed at 72 h. EVO elevated the activities of caspase 3, 8, and 9 in DU145 cells, while in PC3 cells only the activities of caspase 3 and 9 were elevated. EVO also triggered the processing of caspase 3 and 9 in both DU145 and PC3 cells. We demonstrate that roscovitine treatment result in the reversion of G2/M arrest in response to EVO in both DU145 and PC3. However, inhibitory effect of roscovitine on EVO-induced apoptosis could only be observed in DU145 rather than PC3. In DU145, G2/M arrest might be a signal for initiation of EVO-triggered apoptosis. Whereas EVO-triggered PC3 apoptosis might be independent of G2/M arrest. These results suggested that EVO inhibited the growth of prostate cancer cell lines, DU145 and PC3, through an accumulation at G2/M phase and an induction of apoptosis.     

不同除草剂的田间杂草防效及对糜子生长发育的影响

筛选糜子适宜除草剂来防范农田药害,是糜子高效安全生产和改善生态环境亟待解决的关键问题。本研究以粳性糜子品种‘榆糜2号'为材料,探究22种除草剂对糜子田间杂草的防除效果及对糜子生长发育的影响。结果表明: 1)喷施土壤封闭型除草剂谷友、丁草胺、莠去津、苄嘧·丙草胺和茎叶型除草剂苯唑·二甲钠、阔世玛、藤净、陶氏·优先、阔菲后,基本无药害作用,糜子幼苗生长正常,其余除草剂均对糜子有不同程度的药害影响;2)参试的22种除草剂在糜子田中对杂草均表现出一定的防除效果,总体而言,土壤封闭型除草剂的杂草防效相对优于茎叶型除草剂,但所有参试除草剂对糜子株高、功能叶片叶绿素含量、单株穗重均造成不同程度的影响;3)与人工除草相比,参试除草剂均导致糜子产量有不同程度的下降;但与不除草对照相比,部分除草剂有明显的增产增效作用。土壤封闭型除草剂中,谷友、丁草胺、莠去津、苄嘧·丙草胺的杂草防效较好,较不除草对照增产60%以上;茎叶型除草剂中,阔世玛、苯唑·二甲钠的杂草防效较好,较不除草对照增产50%以上。因此,在糜子出苗前可用38%莠去津或44%单嘧磺隆进行土壤封闭处理,或在出苗后喷施茎叶型除草剂3.6%二磺·甲碘隆或55%苯唑·二甲钠,农田杂草防效较好,且对糜子生长发育的负面影响较小。     

Y盒结合蛋白1单克隆抗体的研制、表位测定及其免疫学应用

建立稳定分泌抗人Y盒结合蛋白1单克隆抗体(anti-YB-1 mAb)的杂交瘤细胞株,鉴定其表位与免疫学应用。将重组YB-1蛋白免疫BALB/c小鼠,取脾细胞与Sp2/0骨髓瘤细胞融合。经ELISA法筛选鉴定、定株后采用腹水诱生法制备anti-YB-1 mAb;Protein G亲和层析法纯化mAb,ELISA法测定mAb效价、亚型及相对亲和力。采用抗原表位预测法鉴定anti-YB-1 mAb识别表位所在区域。Western blot和免疫组化鉴定mAb识别内源性YB-1的特异性。经筛选鉴定获得2株稳定分泌anti-YB-1 mAb的杂交瘤细胞(1-D9,3-E8);腹水抗体效价均≥1×10-6,亚型均为IgGl;1-D9和3-E8单抗识别表位分别位于(134-160aa)与(266-303aa)肽段。Western blot、免疫组化结果证实anti-YB-1 mAb能特异性识别内源性YB-1。该研究为YB-1免疫学定性、定量检测方法的建立、肿瘤靶向抗体治疗及进一步探讨YB-1的生物学功能奠定了基础。     

Clonal integration affects allocation in the perennial herb <Emphasis Type="Italic">Alternanthera philoxeroides</Emphasis> in N-limited homogeneous environments

Most work on clonal growth in plants has focused on the advantages of clonality in heterogeneous habitats. We hypothesized (1) that physiological integration of connected ramets within a clone can also increase plant performance in homogeneous environments, (2) that this effect depends on whether ramets differ in ability to take up resources, and (3) that only ramets with relatively low uptake ability benefit. We tested these hypotheses using the perennial amphibious herb Alternanthera philoxeroides. We grew clonal fragments and varied numbers of rooted versus unrooted ramets, connection between the apical and basal parts of fragments, and availability of nitrogen. Patterns of final size and mass of fragments did not support these hypotheses. By some measures, severance did reduce the growth of more apical ramets and increase the growth of less apical ones, consistent with net apical transfer of resources. Rooting of individual ramets strongly influenced their growth: second and third most apical ramets each grew most when they were the most apical rooted ramet, and this pattern was more pronounced under higher nitrogen levels. This adds to the evidence that signalling between ramets is an important aspect of clonal integration. Overall, the results indicate that physiological integration between ramets within clones in homogeneous environments can alter the allocation of resources between connected ramets even when it does not affect the total growth of clonal fragments.