Nitidine chloride inhibited the expression of S phase kinase-associated protein 2 in ovarian cancer cells

Nitidine chloride (NC) has been reported to exert its anti-tumor activity in various types of human cancers. However, the molecular mechanism of NC-mediated tumor suppressive function is largely unclear. In the current study, we used several approaches such as MTT, FACS, RT-PCR, Western blotting analysis, invasion assay, transfection, to explore the molecular basis of NC-triggered anti-cancer activity. We found that NC inhibited cell growth, induced cell apoptosis, caused cell cycle arrest in ovarian cancer cells. Emerging evidence has demonstrated that Skp2 plays an important oncogenic role in ovarian cancer. Therefore, we also explored whether NC exerts its biologic function via downregulation of Skp2 in ovarian cancer cells. We observed that NC significantly inhibited the expression of Skp2 in ovarian cancer cells. Notably, overexpression of Skp2 abrogated the anti-cancer activity induced by NC in ovarian cancer cells. Consistently, downregulation of Skp2 expression enhanced the sensitivity of ovarian cancer cells to NC treatment. Thus, inactivation of Skp2 by NC could be a novel strategy for the treatment of human ovarian cancer.     

自体吸疱表皮移植术结合搔刮术治疗白癜风的临床评价

目的:观察和比较搔刮术结合负压吸疱术和传统负压吸疱术对白癜风复色的疗效。方法:将90例稳定期白癜风患者随机分成搔刮术结合负压吸疱术组(45例)和传统负压吸疱术组(45例),分别给予搔刮术结合负压吸疱术和传统负压吸疱术治疗。治疗后,比较两组的复色情况,是否留有白斑缝隙,并进行白癜风疗效评价。进一步分析皮损部位、性别、临床类型对搔刮术结合负压吸疱术和传统负压吸疱术临床疗效的影响。结果:治疗后,搔刮术结合负压吸疱术组和传统负压吸疱术组在整体疗效无显著性差异(P0.05)。搔刮术结合负压吸疱术组术后获得成片复色比例显著高于传统负压吸疱术组(88.9%vs. 4.4%,P0.001)。不同性别患者接受搔刮术结合负压吸疱术和传统负压吸疱术的疗效比较均无统计学差异(P0.05)。表皮移植术结合搔抓术组和单一表皮移植术组中,皮损发生在颈部、面部相比于躯干部、四肢、手足部的疗效明显更佳,局限型和节段型相比于散发型、肢端型的疗效更佳。结论:自体吸疱表皮移植术结合搔刮术用于稳定期白癜风的复色效果相比于传统自体吸疱表皮移植术疗效更佳。     

Application and future perspective of CRISPR/Cas9 genome editing in fruit crops

Fruit crops, including apple, orange, grape,banana, strawberry, watermelon, kiwifruit and tomato, not only provide essential nutrients for human life but also contribute to the major agricultural output and economic growth of many countries and regions in the world. Recent advancements in genome editing provides an unprecedented opportunity for the genetic improvement of these agronomically important fruit crops. Here, we summarize recent reports of applying CRISPR/Cas9 to fruit crops,including efforts to reduce disease susceptibility, change plant architecture or flower morphology, improve fruit quality traits, and increase fruit yield. We discuss challenges facing fruit crops as well as new improvements and platforms that could be used to facilitate genome editing in fruit crops, including d Cas9-base-editing to introduce desirable alleles and heat treatment to increase editing efficiency. In addition, we highlight what we see as potentially revolutionary development ranging from transgene-free genome editing to de novo domestication of wild relatives. Without doubt, we now see only the beginning of what will eventually be possible with the use of the CRISPR/Cas9 toolkit. Efforts to communicate with the public and an emphasis on the manipulation of consumerfriendly traits will be critical to facilitate public acceptance of genetically engineered fruits with this new technology.     

Strategies for Self-organization: Learning from a Village-level Community-based Conservation Initiative in India

Self-organization is a key condition to the success of community-based conservation initiatives, including those recognized by the Equator Initiative of the UNDP. This paper contributes to emerging scholarship that focuses on community-based conservation in South Asia and in particular examines self-organization strategies within a small-scale community-based conservation initiative in a cross-cultural setting to further understanding about how such initiatives originate, sustain and grow. This is achieved through a case study of the Baripada Forest Protection Initiative in India by utilizing in-depth interviews and focus groups. In addition to certain often-cited strategies for self-organization, the Baripada initiative included unique features of self-organization such as village community design, implementation and adaptation of rules for local natural resources use and conservation, little need for financial support, and significant mobilization of human resources. These strategies, along with emerging social learning opportunities (e.g., a community plant diversity register) inspired by the Baripada initiative, inform and enrich the criteria for designing and evaluating conservation and development initiatives, irrespective of their scale.     

Comparison of the cardiac effects between quinazoline-based α<Subscript>1</Subscript>-adrenoceptor antagonists on occlusion–reperfusion injury

Quinazoline-based compounds such as prazosin and its congeners including doxazosin, bunazosin, and terazosin are widely used as antihypertensive agents. However, there were many clinical observations showing that using these agents may result in higher risk of cardiovascular accidents in recent years. In this study, we compared the effects of four α-adrenoceptor antagonists: prazosin, doxazosin, bunazosin, and terazosin on occlusion–reperfusion injury. Langendorff-perfused rat hearts were pretreated with these four antagonists, and then the left main coronary artery was occluded. After 30 min occlusion, the hearts were reperfused for 2 h and the infarct sizes were measured. Two of the compounds studied, prazosin and doxazosin, apparently increased infarct size, CK-MB, and LDH activities after 2 h reperfusion. In contrast, bunazosin decreased infarct size and those biochemical indicators of cellular damage compared to control hearts. Although infarct size after reperfusion was differently changed by these four α-adrenoceptor antagonists, TUNEL-positive nuclei and caspase-3 protein expressions of all the groups were not significantly different. We supposed that the different effects of these four agents on infarct size came from the difference in necrosis rather than apoptosis.     

Cole Disease Results from Mutations in ENPP1

The coexistence of abnormal keratinization and aberrant pigmentation in a number of cornification disorders has long suggested a mechanistic link between these two processes. Here, we deciphered the genetic basis of Cole disease, a rare autosomal-dominant genodermatosis featuring punctate keratoderma, patchy hypopigmentation, and uncommonly, cutaneous calcifications. Using a combination of exome and direct sequencing, we showed complete cosegregation of the disease phenotype with three heterozygous ENPP1 mutations in three unrelated families. All mutations were found to affect cysteine residues in the somatomedin-B-like 2 (SMB2) domain in the encoded protein, which has been implicated in insulin signaling. ENPP1 encodes ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which is responsible for the generation of inorganic pyrophosphate, a natural inhibitor of mineralization. Previously, biallelic mutations in ENPP1 were shown to underlie a number of recessive conditions characterized by ectopic calcification, thus providing evidence of profound phenotypic heterogeneity in ENPP1-associated genetic diseases.