Analyses of the Chemical Composition of Plasma-Activated Water and Its Potential Applications for Vaginal Health.

This study aimed to elucidate the unique chemical compositions of plasma-activated water (PAW) and the potential antibacterial efficacy of PAW as a novel vaginal cleanser. We analyzed the ion compositions (four anions: F-, Cl-, NO3-, SO42-; five cations: Na+, NH4+, K+, Mg2+, Ca2+) of several formulations of PAW generated at different electrical powers (12 and 24 V) at various treatment time points (1, 10, and 20 min), and stay durations (immediate, 30, and 60 min). As treatment duration increased, hypochlorous acid (HOCl), Ca2+, and Mg2+ concentrations increased and Cl- concentration decreased. Higher electrical power and longer treatment duration resulted in increased HOCl levels, which acts to prevent the growth of general microorganisms. Notably, PAW had no antibacterial effects against the probiotic, Lactobacillus reuteri, which produces lactic acid and is important for vaginal health. These findings indicate that PAW contains HOCl and some cations (Ca2+ and Mg2+), which should help protect against pathogens of the vaginal mucosa and have a cleansing effect within the vaginal environment while not harming beneficial bacteria.

CCL3L3-null status is associated with susceptibility to systemic lupus erythematosus.

The correlation between copy number variation (CNV) and the susceptibility to systemic lupus erythematosus (SLE) has been reported for various immunity-related genes. However, the contribution of CNVs to SLE susceptibility awaits more investigation. To evaluate the copy numbers in immunity-related genes such as TNFAIP3, TNIP1, IL12B, TBX21 (T-bet), TLR7, C4A, C4B, CCL3L1, and CCL3L3, the modified real competitive polymerase chain reaction (mrcPCR) assay was employed, and the association between the copy numbers and SLE susceptibility was analyzed in 334 SLE patients and 338 controls. CCL3L3-null status was significantly associated with SLE susceptibility (OR > 18, P < 0.0001), which remained significant by Bonferroni's correction (corrected P = 0.0007). However, the significant association between C4B low-copy status and SLE susceptibility (OR = 1.6051, P = 0.0331) became non-significant by Bonferroni's correction (corrected P = 0.3938). Except for these results, no other significant association between SLE susceptibility and copy number status in other genes was observed. The CCL3L3-null status may be a significant factor for SLE susceptibility.

Cancer cells undergoing epigenetic transition show short-term resistance and are transformed into cells with medium-term resistance by drug treatment.

To elucidate the epigenetic mechanisms of drug resistance, epigenetically reprogrammed H460 cancer cells (R-H460) were established by the transient introduction of reprogramming factors. Then, the R-H460 cells were induced to differentiate by the withdrawal of stem cell media for various durations, which resulted in differentiated R-H460 cells (dR-H460). Notably, dR-H460 cells differentiated for 13 days (13dR-H460 cells) formed a significantly greater number of colonies showing drug resistance to both cisplatin and paclitaxel, whereas the dR-H460 cells differentiated for 40 days (40dR-H460 cells) lost drug resistance; this suggests that 13dR-cancer cells present short-term resistance (less than a month). Similarly, increased drug resistance to both cisplatin and paclitaxel was observed in another R-cancer cell model prepared from N87 cells. The resistant phenotype of the cisplatin-resistant (CR) colonies obtained through cisplatin treatment was maintained for 2-3 months after drug treatment, suggesting that drug treatment transforms cells with short-term resistance into cells with medium-term resistance. In single-cell analyses, heterogeneity was not found to increase in 13dR-H460 cells, suggesting that cancer cells with short-term resistance, rather than heterogeneous cells, may confer epigenetically driven drug resistance in our reprogrammed cancer model. The epigenetically driven short-term and medium-term drug resistance mechanisms could provide new cancer-fighting strategies involving the control of cancer cells during epigenetic transition.

FAK-Copy-Gain Is a Predictive Marker for Sensitivity to FAK Inhibition in Breast Cancer.

BACKGROUND: Cancers with copy-gain drug-target genes are excellent candidates for targeted therapy. In order to search for new predictive marker genes, we investigated the correlation between sensitivity to targeted drugs and the copy gain of candidate target genes in NCI-60 cells. METHODS: For eight candidate genes showing copy gains in NCI-60 cells identified in our previous study, sensitivity to corresponding target drugs was tested on cells showing copy gains of the candidate genes. RESULTS: Breast cancer cells with Focal Adhesion Kinase (FAK)-copy-gain showed a significantly higher sensitivity to the target inhibitor, FAK inhibitor 14 (F14). In addition, treatment of F14 or FAK-knockdown showed a specific apoptotic effect only in breast cancer cells showing FAK-copy-gain. Expression-profiling analyses on inducible FAK shRNA-transfected cells showed that FAK/AKT signaling might be important to the apoptotic effect by target inhibition. An animal experiment employing a mouse xenograft model also showed a significant growth-inhibitory effect of F14 on breast cancer cells showing FAK-copy-gain, but not on those without FAK-copy-gain. CONCLUSION: FAK-copy-gain may be a predictive marker for FAK inhibition therapy in breast cancer.

Comparing German and Italian food banks: Actors' knowledge on food insecurity and their perception of the interaction with food bank users.

PURPOSE: The purpose of this paper is to investigate food bank actors' knowledge of food insecurity in Germany and in Italy, as well as interactions between food bank actors and food bank users. The study builds on a knowledge framework from an educational context and applies it to food banks. DESIGN/METHODOLOGY/APPROACH: The study uses a qualitative research approach. In all, 22 in-depth interviews were recorded, transcribed and analyzed through inductive qualitative content analysis. FINDINGS: German and Italian food bank actors interviewed had at least situational knowledge on food insecurity. Some actors of the Italian food bank also showed procedural knowledge. Interactions between food bank personnel and users were affected by feelings of gratitude, shame, anger and disappointment. ORIGINALITY/VALUE: The study explores food bank personnel's knowledge on food insecurity, which appears to be a knowledge gap, even though many prior studies were dedicated to food banks and food insecurity. The study contributes to knowledge systematization to provide best practice recommendations for volunteer-user interaction, and suggests how food bank managers and volunteers' knowledge can be improved.

Effect of jeju water on blood glucose levels in diabetic patients: a randomized controlled trial.

Jeju water is the groundwater of Jeju Island, a volcanic island located in Republic of Korea. We investigated whether Jeju water improved glycemic control in patients with diabetes. This was a 12-week single-center, double-blind, randomized, and controlled trial. The subjects daily drank a liter of one of three kinds of water: two Jeju waters (S1 and S2) and Seoul tap water (SS). The primary outcome was the proportion of patients in the per-protocol (PP) population achieving glycated hemoglobin (HbA1c) < 7.0% at week 12. In total, 196 patients were randomized and analyzed in the intention-to-treat (ITT) population (66 consuming S1, 63 consuming S2, and 67 consuming SS); 146 patients were considered in the PP population. There were no significant differences in the primary outcomes of the groups consuming S1, S2, or SS. However, the percentage of patients achieving HbA1c < 8% was significantly higher in the S2 group than in the SS group. In the ITT population, the 12-week HbA1c and fructosamine levels were lower in the S1 group than in the SS group and the 4-, 8-, and 12-week fructosamine levels were lower in the S2 group than in the SS group. Although we failed to achieve the primary outcome, it is possible that the Jeju waters improve glycemic control compared with the Seoul tap water in diabetic patients.

Arvelexin from Brassica rapa suppresses NF-κB-regulated pro-inflammatory gene expression by inhibiting activation of IκB kinase.

BACKGROUND AND PURPOSE: Brassica rapa species constitute one of the major sources of food. In the present study, we investigated the anti-inflammatory effects and the underlying molecular mechanism of arvelexin, isolated from B. rapa, on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and on a model of septic shock induced by LPS. EXPERIMENTAL APPROACH: The expression of Inducible nitric oxide synthase (iNOS) and COX-2, TNF-α, IL-6 and IL-1ß were determined by Western blot and/or RT-PCR respectively. To elucidate the underlying mechanism(s), activation of NF-κB activation and its pathways were investigated by electrophoretic mobility shift assay, reporter gene and Western blot assays. In addition, the in vivo anti-inflammatory effects of arvelexin were evaluated in endotoxaemia induced with LPS. KEY RESULTS: Promoter assays for iNOS and COX-2 revealed that arvelexin inhibited LPS-induced NO and prostaglandin E(2) production through the suppression of iNOS and COX-2 at the level of gene transcription. In addition, arvelexin inhibited NF-κB-dependent inflammatory responses by modulating a series of intracellular events of IκB kinase (IKK)-inhibitor κBα (IκBα)-NF-κB signalling. Moreover, arvelexin inhibited IKKß-elicited NF-κB activation as well as iNOS and COX-2 expression. Serum levels of NO and inflammatory cytokines and mortality in mice challenged injected with LPS were significantly reduced by arvelexin. CONCLUSION AND IMPLICATIONS: Arvelexin down-regulated inflammatory iNOS, COX-2, TNF-α, IL-6 and IL-1ß gene expression in macrophages interfering with the activation of IKKß and p38 mitogen-activated protein kinase, and thus, preventing NF-κB activation.

Eupafolin, a flavonoid isolated from Artemisia princeps, induced apoptosis in human cervical adenocarcinoma HeLa cells.

Although eupafolin, a flavone found in Artemisia princeps Pampanini, has been shown to inhibit the growth of several human cancer cells, its mode of action is poorly understood. In this study, we investigated the pro-apoptotic activities of eupafolin in human cervical carcinoma HeLa cells. It was found that eupafolin induced apoptosis in a dose-dependent manner, as evidenced by DNA fragmentation and the accumulation of positive cells for annexin V. In addition, eupafolin triggered the activations of caspases-3, -6, -7, -8, and -9 and the cleavages of their substrates, such as, poly (ADP-ribose) polymerase and lamin A/C. Furthermore, treatment with eupafolin resulted in a loss of mitochondrial membrane potential (DeltaPsi(m)), increased the release of cytochrome c to the cytosol, and altered the expression levels of B-cell lymphoma 2 (Bcl-2) family proteins. Interestingly, caspase-8, an initiator caspase, was activated after the loss of DeltaPsi(m) and the activations of caspases-3 and -9. Moreover, treatment with z-DEVD-fmk (a specific caspase-3 inhibitor) and the overexpression of Bcl-2 prevented eupafolin-stimulated caspase-8 activation. Altogether, these results suggest that the eupafolin-induced apoptosis in HeLa cells is mediated by caspase-dependent pathways, involving caspases-3, -9, and -8, which are initiated by the Bcl-2-dependent loss of DeltaPsi(m).