As a sensor of cellular energy status, AMP-activated protein kinase (AMPK) is known to play an important role in the pathophysiology of diabetes and its complications. Because AMPK is also expressed in podocytes, it is possible that podocyte AMPK would be an important contributing factor in development of proteinuria. In recent years, despite intensified interest in AMPK in the kidney, studies on the role of AMPK in podocytes are limited. In this review, I will discuss the roles of AMPK in podocytes, which may be involved in development of podocyte dysfunction and proteinuria, and the possibility of AMPK-modulating drugs in prevention and treatment of podocytopathy.

The current study was designed to investigate the effect of Red ginseng extract on development of colonic aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH) in male F344 rats. Five-week old animals received subcutaneous injections of DMH (30 mg/kg body weight) four times, for a period of two weeks in order to induce ACF. The animals were divided into groups fed a diet containing red ginseng extract at three different doses (0.5, 1.0, and 2.0%), respectively. Animals were evaluated for the total number of ACF and total aberrant crypts (AC) per colon detected from methylene blue-stained rat colon. ACF formation was observed in animals in the DMH-treated group. Four-time treatment with DMH induced mean 265.8±48.3 ACF/colon composed of a total of 608.8±110.9 aberrant crypts AC/colon. The numbers of ACF and AC induced by DMH were decreased to 204.4±29.3 and 464.7±70.3 by treatment with 0.5% red ginseng extract. In addition, the number of large ACF (≥4 AC/ACF) was suppressed from 39.9±10.6 ACF/colon in control to 28.5±5.3 ACF/colon in 0.5% red ginseng extract. These results suggested that red ginseng extract exerted a chemopreventive effect on DMH-induced colon cancer by inhibiting development of ACF and AC in F344 rats.

The effects of β-lapachone on gastric secretion were investigated. The pylorus of male Sprague-Dawley rats was ligated and intraduodenally injected with β-lapachone, and the volume, pH, free HCl, and total acidity of gastric fluid were measured 6 hours after the operation. Treatment with β-lapachone resulted in dose-dependent inhibition of gastric secretion Gastric fluid was reduced to 42.9% of control level by 100 mg/kg of β-lapachone, leading to an increase of pH to 6.70 from 1.85 in the control group. In parallel with the increase of pH, at this dosage, free HCl and total acidity decreased to 16.7% and 12.0%, respectively, of control levels. β-Lapachone exhibited ED50 values of 72, 46, and 47 mg/kg for inhibition of gastric volume, free HCl, and total acidity, respectively, implying a superior efficacy on gastric acid to volume. In comparison, pantoprazole (30 mg/kg) reduced the volume, free HCl and total acidity of gastric fluid to 53.0%, 26.0%, and 25.0%, respectively, of control levels, resulting in an increase in pH to 6.36. In the current study, it was confirmed that β-lapachone at an appropriate dose (100 mg/kg) exerted a higher inhibitory effect on gastric secretion than pantoprazole (30 mg/kg), a well-known proton-pump inhibitor. Therefore, it is suggested that β-lapachone could be a candidate compound for prevention or treatment of gastric ulcers induced by diverse psychological and physical stimuli.

In this study, a nanofibrous scaffold was obtained by co-electrospinning poly (3-hydroxybutyrate- co-3-hydroxyvalerate) (PHBV) and collagen in 2,2,2-trifluoroethanol at a ratio of 3/7. The fiber diameters were in the range of 250-600 nm. It was found that PHBV/Collagen (PHCP) nanofibrous scaffold showed greater proliferation than the PHBV nanofibrous scaffold induced by oxidant in NIH3T3 cells. Otherwise, in the early-stage wound-healing mouse model, wound closure was evaluated according to wound size reduction and histology of regenerated skin on the backs of mice. Each of the tissues removed on day 0, 3, 6, 9, 12, 15, and 18 was used for analysis of biochemical and pathological changes. None of the nanofiber-attached mice showed significant difference on the third day, however, from the third day until the ninth day, significantly faster healing was observed in PHCP-attached mice, compared to control wounds in epithelialization, wound contraction, and histopathological examinations. These results strongly support the beneficial effects of biomedical application of PHCP nanofiber in acceleration of the initial phase of wound healing through α-SM actin contraction.

Immunotherapeutic approaches using agonist antibodies or fusion proteins of immunomodulatory molecules significantly inhibit tumor growth and boost cell-mediated immunity. We isolated mRNA from previously reported 1D4 hybridoma cells and amplified the variable regions of the heavy chain (VH) and light chain (VL) genes using reverse-transcriptase polymerase chain reaction. Using a linker, the amplified sequences for the heavy and light chains were each connected to the sequence for a single polypeptide chain that was designed to be expressed. VL and VH fragments were cloned into the pOptiVEC-TOPO vector containing the human CH2-CH3 fragment. Then, 293T cells were transfected with the 1D4 single-chain Fv-Fc (scFv-Fc) constructs. A549 cells were used for presentation of the 1D4 antigen. Flow cytometry was performed for analysis of the secreted 1D4 scFv-Fc constructs. The DNA sequence of 1D4 scFv-Fc was obtained. The 1D4 scFv-Fc constructs were expressed by the transfected 293T cells and secreted into the culture medium. The immunoreactivity of the secreted scFv-Fc construct was lower than that of the murine 1D4 antibody for A549 cells. A 1D4 scFv-Fc construct for immunotherapy was developed.

Macrophages can recognize antigens and microorganisms, and then initiate an appropriate defense. However, there has been a lack of comprehensive information regarding the genes that are modulated by commensal yeasts, including Saccharomyces cerevisiae or Saccharomyces exiguus. In addition, it is not clear to what extent the beneficial yeasts modulate the immune response against microbes and/or microbial toxins. Using DNA microarray, which contains approximately 25,000 genes, we studied interactions between host cells and yeast/bacterial toxin (LPS) by analyzing the transcriptional response of macrophages stimulated by Saccharomyces exiguus and/or Lipopolysaccharides. Thirty three genes were identified to be modulated by more than two folds between groups of macrophage cells. Pathway analysis provided insight into the mutual interactions. Of particular interest was the responses elicited by fungus in murine macrophage cells, including modulation of immunity/defense, cellular signal transduction, cell proliferation/differentiation, and transport. This finding indicates that the yeast induces immune response pathways as well as those associated with cell proliferation and transport. Among the 33 genes identified from the DNA microarray screening, eight genes were further checked by RT-PCR analysis using gene specific primers. Compared to those of negative control, sequential treatment with the yeast strain followed by LPS apparently induced expression of Tnfaip3, IL7R, and CD86, while it inhibited expression of Cxcl10 and CD83. In conclusion, this study identified the genes that are up-regulated by Saccharomyces exiguus. A further study is needed in order to determine whether these genes are modulated at the protein level, and also for their roles in control of immune responses.