Earticle

Nanomedicine constitutes the emerging field of medical applications for nanotechnology such as nanomaterial-based drug delivery systems. This technology may hold exceptional potential for novel therapeutic approaches to liver diseases. Activ ation of apoptosis pathway is a key mechanism by which cytotoxic drugs kill tumor cells. Delivering drugs sele ctively to cancer cells but not to nearby normal cells is a major obstacle in drug therapy. In this study, lithoch olic acid (LCA), a potent anti-cancer drug, is converted to two forms of poly(ethyleneglycol) (PEG) conjugates, viz., PEG-LCA (PL) and lactobionic acid (LBA) conjugated PEG-LCA (LPL). The latter form contains a galacto se ligand in LBA to target the hepatocytes. Both forms are self-assembled to form nanoparticle formulation, and they have high potency than LCA to kill HepG2 cancer cells, sparing normal LO2 cells. Besides, LPL has high specificity to mouse liver cells in vivo after intravenous (IV) injection. Western blot results confirm that the cel l death is occurred through apoptosis induced by LPL nanoparticles. In conclusion, the induction of apoptosis a nd cell death is much more efficient with LPL nanoparticles than LCA molecules as well as good hepatocyte specificity in vitro and in vivo.

Background: Multiple myeloma (MM) is the second most prevalent hematologic malignancy and it is uniformly fatal. Although survival rate has been increased over the last few decades, MM remains as a largely incurable disease with mortality rate. A second generation of kinesin spindle protein (KSP) inhibitor is a new anti-cancer treatment and its targets the mitotic motor kinesin. Methods: MM cell line-KMS20 exhibited cell death, cell cycle arrest and mitochondrial Ca2+ concentrations, mitochondrial ROS level, mitochondrial membrane potential (ψΔm), oxygen consumption and ATP production, under non-treated and SB743921 treated conditions. Results: we report that SB743921 induces mitochondria-mediated cell death via inhibition of the NF-κB signaling pathway, but does not cause cell cycle arrest in KMS20 MM cells. SB743921-mediated inhibition of the NF-κB pathway results in reduced expression of SOD2 and Mcl-1, leading to mitochondrial dysfunction. Moreover, we found that combination treatment with SB743921 and bortezomib induces death in bortezomib- resistant KMS20 cells. Conclusion: Taken together, these data suggest that treatment with SB743921 alone or in combination with bortezomib offers excellent translational potential and promises to be a novel MM therapy.

온라인 소셜 네트워크 서비스가 대중화되고 있는 가운데 개인 정보 보호에 대한 사용자들의 관심이 높아지면서 중앙집중 형 방식이 아닌 P2P 기반 소셜 네트워크 서비스에 대한 연구가 활발히 이루어지고 있다. 소셜 네트워크 분석에 있어서 최단경로 탐색은 매우 중요한데, 본 논문에서는 P2P 기반 SNS 상에서 최단경로 탐색방법을 제안한다. 본 논문에서 제안하는 방법은 시작 노드와 목표 노드에서 번갈아 Query flooding 을 수행하여 두 노드의 매개 노드를 찾아내는 것이다. 이는 일반적인 Query flooding 보다 발생하는 쿼리의 양과 수행시간을 줄여주고 순수 P2P 기반 시스템에서 정확한 최단 경로를 찾아 낼 수 있다.

Trichomonas vaginalis is a flagellated protozoan parasite that causes vaginitis and cervicitis in women and asymptomatic urethritis and prostatitis in men, respectively. Mast cells have been reported to be predominant in the vaginal smears and vaginal walls of patients infected with T. vaginalis. Mitogenactivated protein kinase (MAPK) activated by various stimuli also regulate the transcriptional activity of various cytokine genes in the mast cells. Because of their essential role in intracellular signaling network, also appropriate targets for pharmacological treatment of inflammatory disorders. In this study, we investigated whether MAPK were involved ROS generation and exocytotic degranulation in HMC-1 induced by T. vaginalis-derived secretory products (TvSP). We first examined that TvSP could induce activation of MAPK and NADPH oxidase in HMC-1 cells. Stimulation with TvSP induced phosphorylation of MAPK and p47phox in HMC-1 cells. Phosphorylation of p47phox is main source of ROS generation. Next, to determine involvement activation of MAPK in ROS generation and degranulation in HMC-1 cells induced by TvSP. ROS generation is required for exocytotic degranulation of mast cells induced by TvSP. Stimulation with TvSP induced phosphorylation of p47phox, ROS generation, surface up-regulation of CD63 in human mast cells. CD63 is a marker for exocytosis. Pretreatment with MAPK inhibitors strongly inhibited TvSP-induced ROS generation and exocytotic degranulation. Finally, our results suggest that TvSP could induce intracellular ROS generation and exocytotic degranulation in HMC-1 via MAPK signaling pathway.

There is cumulative evidence that the Akt and Ras are involved in neuronal survival and protection. The Akt and Ras activates, resulting in the regulation of survival proteins such as BAD and Bcl-xL. Thus, Akt/Ras signaling pathway may be one propitious target for treatment of neurological disease. Pulsed electromagnetic field (PEMF) is known to have effects on biological properties, such as differentiation, regulation of transcription factor and cell proliferation. However, the cell protective effect of PEMF exposure is largely unknown. The aim of this study is to understand the underlying mechanisms that PEMF suppressing apoptosis and promoting survival, including PEMF induced neuronal differentiation. In induced human BM-MSCs treated with PEMF, the expression of neural msarkers such as NF-L, NeuroD1 and Tau increased. Moreover, treatment of induced human BM-MSCs with PEMF exposure greatly decreased cell death in the dose and time dependent manner. Additionally, Analysis indicated that PEMF exposure dramatically promoted activities of Akt, Rsk, Creb, Erk, Bcl-xL and Bad phosphorylation. Meanwhile, the PEMF dependent cell protection was notably reversed by pretreatment with LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). Our data suggest that PI3K/Akt/Bad signalling pathway may be a possible mechanism involved in the cell protective effect of PEMF.