Tissue inhibitor of metalloproteinase proteins inhibit teratoma growth in mice transplanted with pluripotent stem cells.

Pluripotent stem cells (PSCs) can serve as an unlimited cell source for transplantation therapies for treating various devastating diseases, such as cardiovascular diseases, diabetes, and Parkinson's disease. However, PSC transplantation has some associated risks, including teratoma formation from the remaining undifferentiated PSCs. Thus, for successful clinical application, it is essential to ablate the proliferative PSCs before or after transplantation. In this study, neural stem cell-derived conditioned medium (NSC-CM) inhibited the proliferation of PSCs and PSC-derived neural precursor (NP) cells without influencing the potential of PSC-NP cells to differentiate into neurons in vitro and prevented teratoma growth in vivo. Moreover, we found that the NSC-CM remarkably decreased the expression levels of Oct4 and cyclin D1 that Oct4 directly binds to and increased the cleaved-caspase 3-positive cell death through the DNA damage response in PSCs and PSC-NPs. Interestingly, we found that NSCs distinctly secreted the tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 proteins. These proteins suppressed not only the proliferation of PSCs in cell culture but also teratoma growth in mice transplanted with PSCs through inhibition of matrix metalloproteinase (MMP)-2 and MMP-9 activity. Taken together, these results suggest that the TIMP proteins may improve the efficacy and safety of the PSC-based transplantation therapy.

Tuberculous peritonitis in the first trimester of pregnancy.

Tuberculous peritonitis in pregnancy is a rare form of extrapulmonary tuberculosis that is not easily diagnosed. The clinical presentations of tuberculous peritonitis are usually non-specific and mimic those of other diseases, such as ovarian malignancy or chronic liver disease, and this non-specificity can cause diagnostic delays and complications. The authors report the case of a 31-year-old primigravida woman who presented with uncontrolled fever, dyspnea, elevated liver enzymes, and mild abdominal distension at 13+2 weeks of gestation. At 14+2 weeks, a therapeutic abortion was conducted and tuberculous peritonitis was confirmed by laparoscopic excisional biopsy of peritoneal nodules and histopathologic examination. The patient recovered on antituberculosis therapy and abdomen and chest follow up radiographic findings have confirmed improvement.

Vitamin D2 suppresses amyloid-ß 25-35 induced microglial activation in BV2 cells by blocking the NF-κB inflammatory signaling pathway.

AIMS: Present emerging world is emphasizing the implication of vitamin D deficiency associated with development of inflammation and neurodegenerative disorder like Alzheimer's disease (AD). The chief neuropathological hallmark of AD is aggregation of amyloid-beta (Aß) peptides surrounding microglial cells in human brain. Microglial activation plays a key role in inflammatory response and neuronal injury. Naturally abundant vitamin D2 (VD2) exhibiting anti-inflammatory activities are yet to explore more. This study has investigated the inhibitory effect of VD2 on inflammatory activities of BV2 microglial cells. MAIN METHODS: Cellular compatibility of VD2 and Aß25-35 protein in treated BV2 microglial cells were measured by CCK-8 assay. Induction of iNOS, COX-2 and NF-κB signaling cascade were measured by western blotting, whereas pro-inflammatory cytokines were measured by ELISA. In addition, generation of ROS was detected by fluorescence intensity. KEY FINDINGS: Morphological observations showed that Aß25-35 induced BV2 cells stimulation noticeably got reduced in VD2 pre-treated group at 24h time period. Anti-inflammatory activities of VD2 was observed demonstrating the inhibition of up-regulated iNOS and COX-2 protein expression further confirmed by attenuating the activated microglia released pro-inflammatory cytokines IL-1ß, IL-6, TNF- α and ROS, while blocking the phosphorylation of NF-κB p65 in nucleus by preventing IκB-α degradation and phosphorylation in cytosol. SIGNIFICANCE: The present study revealed that VD2 blocked the phosphorylation of NF-κB inflammatory signaling pathway in Aß25-35 induced activated BV2 microglial cells by suppressing ROS generation and inflammatory cytokines. Our finding suggests that vitamin D2 has therapeutic potential against inflammation and Alzheimer's disease.

Uterine prolapse in a primigravid woman.

Uterine prolapse during pregnancy is an uncommon condition. It can cause preterm labor, spontaneous abortion, fetal demise, maternal urinary complication, maternal sepsis and death. We report the case of uterine prolapse in a 32-year-old healthy primigravid woman. She had no risk factors associated with uterine prolapse. She was conservatively treated, resulting in a successful vaginal delivery. This report is a very rare case of uterine prolapse in a young healthy primigravid woman, resulting in a successful vaginal delivery.

Neural Stem Cells Restore Hair Growth Through Activation of the Hair Follicle Niche.

Several types of hair loss result from the inability of hair follicles to initiate the anagen phase of the hair regeneration cycle. Modulating signaling pathways in the hair follicle niche can stimulate entry into the anagen phase. Despite much effort, stem cell-based or pharmacological therapies to activate the hair follicle niche have not been successful. Here, we set out to test the effect of neural stem cell (NSC) extract on the hair follicle niche for hair regrowth. NSC extracts were applied to the immortalized cell lines HaCaT keratinocytes and dermal papilla cells (DPCs) and the shaven dorsal skin of mice. Treatment with NSC extract dramatically improved the growth of HaCaT keratinocytes and DPCs. In addition, NSC extract enhanced the hair growth of the shaven dorsal skin of mice. In order to determine the molecular signaling pathways regulated by NSCs, we evaluated the expression levels of multiple growth and signaling factors, such as insulin-like growth factor-1 (IGF-1), hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), transforming growth factor-ß (TGF-ß), and bone morphogenetic protein (BMP) family members. We found that treatment with an NSC extract enhanced hair growth by activating hair follicle niches via coregulation of TGF-ß and BMP signaling pathways in the telogen phase. We also observed activation and differentiation of intrafollicular hair follicle stem cells, matrix cells, and extrafollicular DPCs in vivo and in vitro. We tested whether activation of growth factor pathways is a major effect of NSC treatment on hair growth by applying the growth factors to mouse skin. Combined growth factors, including TGF-ß, significantly increased the hair shaft length and growth rate. DNA damage and cell death were not observed in skin cells of mice treated with the NSC extract for a prolonged period. Overall, our data demonstrate that NSC extract provides an effective approach for promoting hair growth by directly regulating hair follicle niches through TGF-ß and BMP signaling pathways as well as induction of core growth factors.

Eritadenine from Edible Mushrooms Inhibits Activity of Angiotensin Converting Enzyme in Vitro.

The inhibition of angiotensin converting enzyme (ACE) activity was determined in vitro by mushroom-derived eritadenine (EA), which was analyzed in 11 principal Korean edible mushrooms. EA inhibited ACE activity with 0.091 µM IC50, whereas the IC50 of captopril (CP), which is a reference compound, was 0.025 µM. Kinetic measurements of ACE reaction in the substrate of hippuryl-l-histidyl-l-leucine (HHL) with or without EA revealed that the Vmax (0.0465 O.D/30 min) was unchanged, but the the Km increased from 2.063 to 3.887 mM, indicating that EA competes with HHL for the active site. When EA was analyzed by HPLC, Lentinus edodes with a soft cap contained the highest amount EA (642.8 mg%); however, Phellinus linteus with a hard cap contained the least amount of EA (9.4 mg%). These results indicate that EA was a strong competitive inhibitor for ACE, and edible mushrooms with soft caps contained a significant amount of EA.

Antiproliferative Action of Conjugated Linoleic Acid on Human MCF-7 Breast Cancer Cells Mediated by Enhancement of Gap Junctional Intercellular Communication through Inactivation of NF- κ B.

The major conjugated linoleic acid (CLA) isomers, c9,t11-CLA and t10,c12-CLA, have anticancer effects; however, the exact mechanisms underlying these effects are unknown. Evidence suggests that reversal of reduced gap junctional intercellular communication (GJIC) in cancer cells inhibits cell growth and induces cell death. Hence, we determined that CLA isomers enhance GJIC in human MCF-7 breast cancer cells and investigated the underlying molecular mechanisms. The CLA isomers significantly enhanced GJIC of MCF-7 cells at 40 µ M concentration, whereas CLA inhibited cell growth and induced caspase-dependent apoptosis. CLA increased connexin43 (Cx43) expression both at the transcriptional and translational levels. CLA inhibited nuclear factor- κ B (NF- κ B) activity and enhanced reactive oxygen species (ROS) generation. No significant difference was observed in the efficacy of c9,t11-CLA and t10,c12-CLA. These results suggest that the anticancer effect of CLA is associated with upregulation of GJIC mediated by enhanced Cx43 expression through inactivation of NF- κ B and generation of ROS in MCF-7 cells.

Performance analysis of the ARCHITECT anti-cyclic citrullinated peptide antibody in the diagnosis of rheumatoid arthritis.

BACKGROUND: Anti-cyclic citrullinated peptide (CCP) antibody is emerging as an important diagnostic marker for rheumatoid arthritis (RA). We evaluated the analytical and diagnostic performance of the ARCHITECT anti-CCP (Abbott Diagnostics), a new fully automated chemiluminescent microparticle immunoassay. METHODS: Serum samples from 69 patients with RA and 86 non-RA patients were used to evaluate the performance of the ARCHITECT anti-CCP assay, and the results were compared with those of EliA CCP (Phadia). The optimal cut-off value was calculated using receiver operating characteristic (ROC) curve analysis. RESULTS: Within-run and total imprecision (%CV) of the ARCHITECT anti-CCP were <6% and good linearity was observed over the claimed range. The areas under the ROC curves for the ARCHITECT anti-CCP and EliA CCP were 0.90 and 0.89, respectively. The sensitivity and specificity were 76.8% and 95.3% for the ARCHITECT anti-CCP and 78.3% and 95.3% for EliA CCP using the manufacturer's cut-off thresholds. Both assays showed sensitivity of 84.1% and specificity of 94.2% using the optimal cut-off values. CONCLUSIONS: The analytical performance of the ARCHITECT anti-CCP was satisfactory and diagnostic performance was comparable to that of EliA CCP. The use of optimal cut-off thresholds can yield higher sensitivity with minimal loss of specificity.

Growth inhibition of foodborne and pathogenic bacteria by conjugated linoleic acid.

The influence of conjugated linoleic acid (CLA) on the growth of some foodborne and pathogenic bacteria was examined. A potassium salt of CLA (CLA-K) was tested against three Gram-positive strains ( Bacillus cereus , Staphylococcus aureus , and Streptococcus mutans ) and five Gram-negative strains ( Pseudomonas aeruginosa , Salmonella typhimurium , Vibrio parahemolyticus , Klebsiella pneumoniae , and Proteus mirabilis ). CLA-K-mediated growth inhibition was evident for all tested strains, particularly the Gram-positive strains. The IC(50) value of CLA-K was 0.3 mM for B. cereus, 1.2 mM for S. aureus, and 0.3 mM for S. mutans, whereas the value was 1.2 mM for K. pneumoniae, 1.2 mM for P. aeruginosa, 1.8 mM for S. typhimurium, 1.8 mM for V. parahemolyticus, and 2.4 mM for P. mirabilis. The CLA-K delayed the growth of all the tested strains at lower CLA-K concentrations, but completely inhibited the growth at higher concentrations. All cells grown in the medium containing CLA-K contained CLA in their membranes and exhibited irregular cell surface and cell disruption, which were greater in Gram-positive than Gram-negative strains. Higher lactic dehydrogenase activity (LDH), protein content, and malondialdehyde (MDA) content were evident in Gram-positive strains than in Gram-negative strains. These results suggest that the broad spectrum of growth inhibition by CLA mediated through the lipid peroxidation of CLA in the membranes and in the medium.

[Effects of taping therapy on the deformed angle of the foot and pain in hallux valgus patients].

PURPOSE: This study was to examine the effects of Taping therapy on the deformed angle of the foot and pain in hallux valgus patients. METHOD: The subjects were 24 feet from 15 patients who were diagnosed withhallus valgus at the orthopedic department of K University Hospital in Seoul. Taping therapy was conducted 15 times overall during a four-week period. Data was analyzed using descriptive statistics and t-test. RESULT: The deformed angle of the foot of the hallus valgus patients significantly improved from 21.95 (4.38) to 18.75 (4.80) after Taping therapy. Pain significantly decreased from 4.73 (1.56) to 3.45 (2.21) after Taping therapy. CONCLUSION: The result shows that Taping therapy is effective in improving the deformed angle of the foot and in decreasing pain in the hallux valgus patients.