Suppressive Effects of a Truncated Inhibitor K562 Protein-Derived Peptide on Two Proinflammatory Cytokines, IL-17 and TNF-α.

Inhibitor K562 (IK) protein was first isolated from the culture medium of K562 cells, a leukemia cell line, and is an inhibitory regulator of interferon-γ-induced major histocompatibility complex class II expression. Recently, exogenous truncated IK (tIK) protein showed potential as a therapeutic agent for inflammation-related diseases. In this study, we designed a novel putative anti-inflammatory peptide derived from tIK protein based on homology modeling of the human interleukin-10 (hIL-10) structure, and investigated whether the peptide exerted inhibitory effects against proinflammatory cytokines such as IL-17 and tumor necrosis factor-α (TNF-α). The peptide contains key residues involved in binding hIL-10 to the IL-10 receptor, and exerted strong inhibitory effects on IL- 17 (43.8%) and TNF-α (50.7%). In addition, we used circular dichroism spectroscopy to confirm that the peptide is usually present in a random coil configuration in aqueous solution. In terms of toxicity, the peptide was found to be biologically safe. The mechanisms by which the short peptide derived from human tIK protein exerts inhibitory effects against IL-17 and TNF-α should be explored further. We also evaluated the feasibility of using this novel peptide in skincare products.

Insight into the bovine milk peptide LPcin-YK3 selection in the proteolytic system of Lactobacillus species.

Antimicrobial peptides are class of small, positively charged peptides known for their broad-spectrum antimicrobial activity. Antimicrobial activities for most antimicrobial peptides have largely remained elusive, particularly in the lactic acid bacteria. However, recently our investigation using LPcin-YK3, an antimicrobial peptide from bovine milk, suggests that in vitro antimicrobial activity was reduced over 100-fold compared with pathogenic bacteria. Additionally, for the structural study of how antimicrobial peptide undergoes its reaction at the proteolytic pathway of lactic acid bacteria based on degradation assay and propidium iodide staining, we performed molecular docking for interaction between oligopeptide-binding protein A and LPcin-YK3 peptide. Given that degradation related to the LPcin-YK3 peptide in lactic acid bacteria proteolytic system, the inhibitory inactivity of LPcin-YK3 against beneficial lactic acid bacteria strains may be one of the primary pharmacological properties of recombinant peptide discovered in bovine milk. These results provide structural and functional insights into the proteolytic mechanism and possibility as a putative substrate of oligopeptide-binding protein A in respect of LPcin-YK3 peptide.

Nanoemulsion Vehicles as Carriers for Follicular Delivery of Luteolin.

Luteolin (3',4',5,7-tetrahydroxyflavone), a type of flavonoid found in medicinal herbs and vegetables, has been of great interest due to its antioxidative, anti-inflammatory, and anticarcinogenic effects. Despite these beneficial biological properties, the ease with which luteolin forms molecular crystals in conventional aqueous formulations has hampered much wider applications. In this study, we introduce an oil-in-water (O/W) nanoemulsion vehicle system for enhanced follicular delivery of luteolin. The luteolin-loaded nanoemulsion, which had an average hydrodynamic size of approximately 290 nm, was produced by the assembly of poly(ethylene oxide)-block-poly(ε-caprolactone) and lecithin at the O/W interface. The luteolin-loaded nanoemulsion showed outstanding stability against drop coalescence and aggregation. This was confirmed from the slight drop size increase after repeated freeze-thaw cycling and long-term storage. Moreover, in vivo hair growth evaluation demonstrated that the luteolin-loaded nanoemulsions fabricated in this study possessed the hair growth-promotion activity, which is comparable with the case of using a luteolin solution in an organic solvent.

Synthesis and biological evaluation of arginyl-diosgenin conjugate as a potential bone tissue engineering agent.

Water-soluble arginyl-diosgenin (Arg-DG) conjugate was designed, synthesized, and evaluated for a biological activity. The Arg-DG conjugate was characterized using FT-IR, 1 H NMR, 13 C NMR, and HPLC-MS analyses, followed by a biological activity evaluation. Compared with DG, the Arg-DG conjugate showed a decreased cytotoxicity against L929 cells and an increased antiproliferative activity against hepatocellular cells. The safety of the Arg-DG conjugate was confirmed using the highly sensitive Alamar Blue assay, which indicated that it increased the cellular metabolic activity at suitable concentrations. The Arg-DG conjugate promoted an endothelial tube formation as well. Furthermore, the Arg-DG conjugate improved the bone morphogenetic protein 2 (BMP2)-induced osteoblastic differentiation with synergistic effects on alkaline phosphatase (ALP) activity and mineralization. These results suggest that the Arg-DG conjugate developed in this study has great potentials for biomedical applications such as bone tissue engineering.

Diffuse infiltrative hepatocellular carcinomas in a hepatitis B-endemic area: diagnostic and therapeutic impediments.

BACKGROUND/AIMS: Clinical features of diffuse infiltrative hepatocellular carcinoma (D-HCC) are distinct from those of mass-forming HCCs, and also dependent on etiologic viruses. Moreover, despite a regular HCC-surveillance in those with chronic liver diseases, patients sometimes present with advanced D-HCCs. Thus, in the present study, we were to assess the risk factors, mode of diagnosis and prognosis of D-HCCs in a hepatitis B virus-endemic area. METHODOLOGY: From January to June 2003, 35 patients who had been newly diagnosed as having D-HCC were enrolled. Their clinical characteristics were compared with those with other types of HCCs, who had been enrolled during the same period. Survival rates were analyzed using Kaplan-Meier method and Cox proportional hazard model. RESULTS: D-HCC patients were younger and more commonly positive for HBsAg than those with other types of HCCs. During a regular follow-up, these tumors were not readily detectable in ultrasonography. Transarterial chemoembolization was beneficial in patients with good liver function as compared to supportive care, while this was not evident in those with poor hepatic reserve. CONCLUSIONS: D-HCCs are not readily diagnosed using ultrasonography. These tumors are mostly resistant to treatment, while transarterial chemoembolization might be applied in patients with good liver function.

[A case of infiltrative hepatocellular carcinoma with main portal vein tumor thrombosis successfully treated by transarterial chemoembolization].

A 63-year-old HBsAg-positive male patient was admitted for the evaluation of a liver mass that was detected on ultrasonography. Spiral computed tomography (CT) revealed infiltrative hepatocellular carcinoma (HCC) in the right hepatic lobe with main portal vein tumor thrombosis. His liver function was Child-Pugh class A and the serum alpha fetoprotein level was 7,400 ng/mL. Transarterial chemoembolization (TACE) via the right hepatic artery was performed. Following 3 sessions of TACE every 2 months, spiral CT revealed no evidence of viable tumor. The thrombi within the main portal vein disappeared with performing localized hepatic infarction at the site of the previous tumor. He is still alive 15 months after the third TACE without evidence of recurred tumor and his liver function remains well preserved. This case suggests that TACE might be effective and safe even in the patients with infiltrative HCC with main portal vein tumor thrombosis, if the extent of the tumor is limited and the liver function and portal flow via the collaterals are preserved.