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This study introduces an innovative approach to automatically analyzing 1H nuclear magnetic resonance (NMR) data, integrating a quantum mechanical spectral analysis (QMSA) to enhance efficiency over manual data analysis in NMR. This proposed digital platform features a standardized quantitative NMR (qNMR) procedure, digital Reference Spectra within a spectral library, and a visualized interactive interface for streamlined, automated NMR data analysis. This digital platform significantly reduces the need for manual intervention and shows promise in using spectral fitting to compare the calculated spectrum derived from a digital Reference Spectrum with an experimental spectrum. The digital platform excels in processing data of both single chemical and mixture, delivering accurate results, and positioning it as an essential tool for automatic 1H qNMR analyses. Case studies highlight the digital platform's effectiveness, demonstrating its wide-ranging applicability. This shows that the proposed digital platform, based on a qNMR-based QMSA approach, offers reliable qualitative and quantitative analyses and paves the way for integrating digital reference standards into future compendial tests. [ABSTRACT FROM AUTHOR]

To evaluate the feasibility and safety of laparo-endoscopic single-site surgery (LESS) compared with conventional laparoscopic surgery (CLS) for early-stage endometrial cancer. Patients with clinical stage IA, IB, grade 1–3 endometrial cancer were randomly assigned to undergo LESS or CLS. The primary endpoint was the non-inferiority of LESS to CLS in terms of operation time and the number of resected pelvic lymph nodes. We set the non-inferior margin of the operation time as within 15% (24 min) and the number of resected pelvic lymph nodes as within 20% (5.2 lymph nodes). There was no significant difference between the LESS group (n = 53) and the CLS group (n = 54) in terms of age, weight, body mass index, parity, menopausal status, history of abdominal surgery, and preoperative CA-125 levels. The total operation time was comparable between the two groups. On average, 4.6 fewer pelvic lymph nodes were retrieved in the LESS group, which was within the non-inferiority margin. There were no significant differences in the incidence of intra- and postoperative complications, estimated blood loss, and postoperative hospital stay between the two groups. After a median follow-up time of 34 months (range, 2–242), the progression-free survival rates were 96.2% and 98.1% (P = 0.55) in the LESS group and the CLS group, and the overall survival rates were 98.1% and 100.0% (P = 0.31), respectively. LESS surgical staging was non-inferior to CLS and had acceptable feasibility, safety, and efficacy for the surgical management of early-stage endometrial cancer. Trial registration: Clinicaltrial.gov identifier number: NCT01679522 • There was no difference in surgical outcomes in LESS and CLS group. • Both groups showed similar oncologic outcomes in terms of OS and PFS. • LESS surgical staging was non-inferior to CLS and had acceptable feasibility and safety for the surgical management of early-stage endometrial cancer. [ABSTRACT FROM AUTHOR]

Given the increasing demand for hydrogen, owing to its environmentally friendly nature, it is important to explore efficient methods for hydrogen production. This study investigates dark-fermentative hydrogen production by the co-digestion of food waste and sewage sludge. Both wastes were subjected to alkali pretreatment (at pH 13) to enhance biodegradability. Batch tests were conducted to enhance hydrogen production from food waste and sewage sludge under various volatile solid (VS) concentrations of 1.5–5% and food waste to sewage sludge mixing ratios of 0:100–100:0. We found that alkali pretreatment was effective in increasing hydrogen yields. The maximum specific hydrogen production rate of 163.8 mL H2/g volatile suspended solid/h was obtained at a VS concentration of 5.0% and food waste composition of 62.5%. Additionally, VS concentration of 2.8% and food waste composition of 100% yielded a maximum hydrogen production potential of 152.1 mL H2/g VS. Our findings indicate that food waste and sewage sludge with alkali pretreatment are potential substrates to produce biohydrogen. [ABSTRACT FROM AUTHOR]

Context • Pruritus is a common skin disease among older adults. With aging, there is a decrease in skin elasticity and thickness, and vascular changes occur that decrease the skin’s ability to retain moisture. Objective • To investigate the effects of aromatherapy massage on pruritis and stress levels in older women. Design • This was a nonequivalence, pre-post, quasiexperimental study. To enhance the appropriateness and accuracy of the intervention, a pilot study was conducted before the main study. Setting • The participants were recruited from six senior citizens’ centers in Changwon City, Gyeongnam, South Korea. Participants • The participants were 64 women ≥65 years of age with an average age of 80.7 years and 79.7 years in the intervention and the control groups, respectively. Intervention • The intervention comprised aromatherapy massage with a blend of three essential oils: 1 mL of lavender, 0.25 mL of Roman chamomile, and 0.25 mL of sandalwood diluted to 1.5% with a sweet-almond carrier oil. The control group received massages with 0.25% sandalwood oil. Outcome Measures • The symptom score table of the Pruritus Score Scale was used to measure the degree, area, and frequency of pruritus and its impact on everyday life. The study also measured skin hydration levels using moisture-measuring module sensor, skin pH using the Howskin device, and stress using the Perceived Stress Scale. Results • Of the 64 initial participants, 5 dropped out of the study, resulting in 59 being included in the analysis. A significant difference was found between the intervention and control groups regarding relief of pruritus (U = 302.5, P = .039) and stress levels (U = -6.36, P < .001). No adverse effects were observed. Conclusions • Aromatherapy massage can be an effective intervention to decrease pruritus and stress in older women. Further studies with larger samples that also include men are required to confirm the generalizability of these results. [ABSTRACT FROM AUTHOR]

Intermediate conductance calcium-activated potassium channel (KCNN4) in cancer: Emerging roles and therapeutic potentials. [Display omitted] The KCa3.1 channel (also known as the KCNN4, IK1, or SK4 channel) is an intermediate-conductance calcium-activated potassium channel that regulates the membrane potential and maintains calcium homeostasis. Recently, KCa3.1 channels have attracted increasing attention because of their diverse roles in various types of cancers. In cancer cells, KCa3.1 channels regulate key processes, including cell proliferation, cell cycle, migration, invasion, tumor microenvironments, and therapy resistance. In addition, abnormal KCa3.1 expression in cancers is utilized to distinguish between tumor and normal tissues, classify cancer stages, and predict patient survival outcomes. This review comprehensively examines the current understanding of the contribution of KCa3.1 channels to tumor formation, metastasis, and its mechanisms. We evaluated the potential of KCa3.1 as a biomarker for cancer diagnosis and prognosis. Finally, we discuss the advances and challenges of applying KCa3.1 modulators in cancer treatment and propose approaches to overcome these obstacles. In summary, this review highlights the importance of this ion channel as a potent therapeutic target and prognostic biomarker of cancer. [ABSTRACT FROM AUTHOR]

This study attempted to identify the influence of good death perception, moral anguish, and End-of-life (EOL) care attitudes on the End-of-life (EOL) care performance of General Hospital Health Managers (GHHMs). This study was a quantitative and descriptive survey. The respondents of this study were 156 GHHMs working in three general hospitals with 300 beds or more and one general hospital with 100 beds or more in one of the cities in South Korea. The survey data were obtained from September 20 to October 20, 2021, and a total of 156 responses were analyzed by multiple linear regression using IBM SPSS/WIN 24.0 program. Results of the study revealed that it can be said that the higher the good death perception and the higher the moral anguish, the better the EOL care performance. The total explanatory power was 23.4%, and good death perception and moral distress explained EOL care performance by 23.4%. Furthermore, the general hospital managers' good health perception, moral anguish improved the performance and work satisfaction among nurses. It was necessary to implement a systematic EOL care education program to facilitate quality EOL care. Communication problems and lack of time are obstacles to EOL care performance, so hospital managers and the head of the nursing department provide communication-related education to EOL care GHHMs and allocate appropriate manpower so that GHHMs can actively and efficiently perform EOL care. It can be said that the higher the good death perception, the higher the moral anguish, and the higher the degree of EOL care performance. This study was meaningful in revealing good death perception, and moral agony in clinical practice have a significant effect on EOL care performance. [ABSTRACT FROM AUTHOR]

A new sequential post‐polymerization modification route has been developed for the synthesis of multifunctional polymers from a simple aldehyde polymer. In the first modification step, a template polymer derived from the radical polymerization of 4‐vinyl benzaldehyde undergoes Rh‐catalyzed hydroacylation with alkenes to furnish a group of ketone polymers. In the second modification step, Schiff base formation with alkoxy ammonium salts introduces a second group—an oxime functionality. Both the steps are highly efficient, introducing evenly distributed dual functionalities at the same position. [ABSTRACT FROM AUTHOR]

A real-time reverse transcription polymerase chain reaction (RT-qPCR) assay that does not require Emergency Use Authorization (EUA) reagents was tested and validated for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the early stages of the outbreak of coronavirus disease 2019 (COVID-19) in the Republic of Korea. Early diagnosis of COVID-19 enables timely treatment and the implementation of public health measures. We validated the sensitivity, specificity, precision, linearity, accuracy, and robustness of the RT-qPCR assay for SARS-CoV-2 detection and compared its performance with that of several EUA-approved kits. Our RT-qPCR assay was highly specific for SARS-CoV-2 as demonstrated by not amplifying 13 other viruses that cause respiratory diseases. The assay showed high linearity using a viral isolate from a patient with known COVID-19 as well as plasmids containing target SARS-CoV-2 genes as templates. The assay showed good repeatability and reproducibility with a coefficient of variation of 3%, and a SARS-CoV-2 limit of detection of 1 PFU/mL. The RT-qPCR-based assay is highly effective and can facilitate the early diagnosis of COVID-19 without the use of EUA-approved kits or reagents in the Republic of Korea. [ABSTRACT FROM AUTHOR]

Background Pineal parenchymal tumors are exceedingly rare brain tumors responsible for less than 1% of all adult primary intracranial malignancies in the United States. In this study, we describe the clinicopathologic features, management, and outcomes of patients with pineal parenchymal tumor of intermediate differentiation (PPTID). Methods We describe a single-center, multidisciplinary team experience in managing PPTID patients over a 15-year period (January 2000 to January 2015) at The University of Texas MD Anderson Cancer Center (MDACC). Pathology was reviewed by the pathology collaborators (A.G. and G.N.F.) and retrospective chart review was performed for treatment and clinical outcomes. Results We identified 17 patients (9 male) with diagnosis of PPTID. Median age at diagnosis of PPTID was 37 years (range, 15-57 years). Follow-up ranged from 0.1 to 162.8 months with 6 reported deaths. Most patients presented with headaches and diplopia. Three patients had neuroaxial dissemination at initial diagnosis, and recurrence of tumor was common (7/16) despite treatment. Conclusions No clear prognostic factors were identified in this series. Extension of resection showed a trend toward improved survival. PPTID with neuroaxial dissemination benefits from aggressive initial treatment including craniospinal irradiation and adjuvant chemotherapy, whereas localized disease may be treated traditionally with maximum debulking followed by adjuvant radiotherapy alone. Long-term monitoring is recommended for neurotoxicity and/or late recurrence. [ABSTRACT FROM AUTHOR]

Background: Banhasasim-tang (BHSST) is a classic herbal formulation in traditional Chinese medicine widely used for gastrointestinal (GI) tract motility disorder. We investigated the effects of BHSST on the pacemaker potentials of cultured interstitial cells of Cajal (ICCs) in small intestine in vitro and its effects on GI motor functions in vivo. Methods: We isolated ICCs from the small intestines and recorded pacemaker potentials in cultured ICCs with the whole-cell patch-clamp configuration in vitro. Intestinal transit rates (ITR%) were investigated in normal mice and GI motility dysfunction (GMD) mouse models in vivo. Results: BHSST (20–50 mg/mL) depolarized pacemaker potentials and decreased their amplitudes in a concentration-dependent manner. Pretreatment with methoctramine (a muscarinic M2 receptor antagonist) did not inhibit BHSST-induced pacemaker potential depolarization. However, when we applied 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP; a muscarinic M3 receptor antagonist), BHSST-induced effects were blocked. Pretreatment with Y25130 (a 5-HT3 receptor antagonist) blocked BHSST-induced effects in ICCs. In addition, when we applied 4-DAMP and Y25130 together, BHSST-induced effects were completely blocked. Pretreatment with Ca2+-free solution or thapsigargin inhibited BHSST-induced effects. Moreover, BHSST blocked both the transient receptor potential melastatin (TRPM) 7 and voltage-sensitive calcium-activated chloride (anoctamin-1, ANO1) channels. In normal mice, ITR% values were significantly increased by BHSST in a dose-dependent manner. The ITR% of GMD mice was significantly reduced relative to those of normal mice, which were significantly reversed by BHSST in a dose-dependent manner. Conclusion: These results suggested that BHSST depolarizes the pacemaker potentials of ICCs in a dose-dependent manner through the M3 and 5-HT3 receptors via internal and external Ca2+-dependent and TRPM7- and ANO1-independent pathways in vitro. Moreover, BHSST increased ITR% in vivo in normal mice and GMD mouse models. Taken together, the results of this study showed that BHSST had the potential for development as a prokinetic agent in GI motility function. [ABSTRACT FROM AUTHOR]

Background: Rikkunshito has been used to treat gastrointestinal (GI) disorders. The purpose of this study was to investigate the effects of Rikkunshito, a traditional Japanese herbal medicine, on the pacemaker potentials of interstitial cells of Cajal (ICCs) from the small intestines of mice. Methods: We isolated ICCs from the small intestines of mice, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs and membrane currents. Results: Rikkunshito depolarized ICC pacemaker potentials in a dose-dependent manner. Pretreatment with GSK1614343 or (D-Lys3)-growth hormone-releasing peptide-6 inhibited Rikkunshito-induced depolarization of pacemaker potentials. Intracellular GDP-β-S inhibited Rikkunshito-induced effects. In Ca2+-free solution or in the presence of thapsigargin, Rikkunshito did not depolarize pacemaker potentials. Moreover, in the presence of U-73122 or xestospongin C, Rikkunshito-induced effects were inhibited. However, in the presence of staurosporine, Go6976 or Rottlerin, Rikkunshito depolarized pacemaker potentials. Furthermore, Rikkunshito inhibited both transient receptor potentials melastatin 7 (TRPM7) and Ca2+-activated Cl– channels (ANO1) currents. Conclusion: Rikkunshito depolarized pacemaker potentials of ICCs via ghrelin receptor and G protein through internal or external Ca2+-, phospholipase C-, and inositol triphosphate-dependent and protein kinase C-, TRPM7-, and ANO1-independent pathways. The study shows that Rikkunshito may alleviate GI motility disorders through its depolarizing effects on ICCs. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a gastrointestinal (GI) disease accompanied by changes in bowel habits without any specific cause. Gintonin is a newly isolated glycoprotein from ginseng that is a lysophosphatidic acid (LPA) receptor ligand. To investigate the efficacy and mechanisms of action of gintonin in IBS, we developed a zymosan-induced IBS murine model. In addition, electrophysiological experiments were conducted to confirm the relevance of various ion channels. In mice, gintonin restored colon length and weight to normal and decreased stool scores, whilst food intake remained constant. Colon mucosal thickness and inflammation-related tumor necrosis factor-α levels were decreased by gintonin, along with a reduction in pain-related behaviors. In addition, the fecal microbiota from gintonin-treated mice had relatively more Lactobacillaceae and Lachnospiraceae and less Bacteroidaceae than microbiota from the control mice. Moreover, gintonin inhibited transient receptor potential vanilloid (TRPV) 1 and TRPV4 associated with visceral hypersensitivity and voltage-gated Na+ 1.5 channels associated with GI function. These results suggest that gintonin may be one of the effective components in the treatment of IBS. [ABSTRACT FROM AUTHOR]

Bioactive peptides (BPs) play key roles in regulating cellular metabolism, and are therefore of special interest to the nutraceutical and pharmaceutical industries. Protein digestion is a major route to production of BPs. Biocatalyst-aided processes are advantageous in that they generate protein hydrolysates with high specificity that are non-immunogenic and resistant to proteolysis in the gastrointestinal tract. On the other hand, these approaches are limited by their high production cost and poor diversity of peptides, as well as the requirement for sophisticated analysis for functional validation and scale-up. The recent development of microbial genome and protein databases, together with in silico analysis, have enabled BP design with bioavailability and the identification of new routes for the isolation of BPs from natural resources. In this review, we focus on recent developments in native BP targeting informatics, novel microbial protease mining, and screening methods, which together will accelerate the development of genome-based microbial routes to therapeutic BPs that promote human health and nutrition. [ABSTRACT FROM AUTHOR]

Abstract Reverse electrodialysis (RED) has vast potential as a clean, nonpolluting, and sustainable renewable energy source; however, pilot-scale RED studies employing real waters remain rare. This study reports the largest RED (1000 cell pairs, 250 m2) with municipal wastewater effluent (1.3–5.7 mS/cm) and seawater (52.9–53.8 mS/cm) as feed solutions. The RED stack was operated at a velocity of 1.5 cm/s and the pilot plant produced 95.8 W of power (0.38 W/m2 total membrane or 0.76 W/m2 cell pair). During operation of the RED, the inlet design of the stack, comprising thin spacers, and the water dissociation reaction at the cathode were revealed as vulnerabilities of the stack. Specifically, pressure drops at the fluid inlet parts had the most detrimental effects on power output due to clogged spacers around the inlet parts. In addition, precipitates resulting in inorganic fouling were inevitable during the water dissociation reaction due to significant potential generated by the stack in the cathode chamber. Na+ and Cl− accounted for the majority of ions transferred from seawater to wastewater effluent through ion exchange membranes (IEMs). Moreover, some divalent cations in seawater, Mg2+ and Ca2+, were also transferred to the wastewater effluent. Some organics with relatively low molecular weights in the wastewater effluent passed through the IEMs, and their hydrophobic properties elevated the specific UV absorbance (SUVA) level in the seawater. Highlights • A 1000-cell-pair RED with wastewater effluent and seawater is presented. • RED operation achieved a power output of 96 W (0.76 W/m2 cell pair). • Dissolved organic carbon with low molecular weights passed through the IEMs. • Precipitates were observed on the shielding CEM and cathode in the cathode chamber. [ABSTRACT FROM AUTHOR]

Fibromodulin (FMOD) is a proteoglycan present in extracellular matrix (ECM). Based on our previous findings that FMOD controls myoblast differentiation by regulating the gene expressions of collagen type I alpha 1 (COL1α1) and integral membrane protein 2 A (Itm2a), we undertook this study to investigate relationships between FMOD and calcium channels and to understand further the mechanism by which they control myoblast differentiation. Gene expression studies and luciferase reporter assays showed FMOD affected calcium channel gene expressions by regulating calcium channel gene promoter, and patch-clamp experiments showed both L- and T-type calcium channel currents were almost undetectable in FMOD knocked down cells. In addition, gene knock-down studies demonstrated the COL1α1 and Itm2a genes both regulate the expressions of calcium channel genes. Studies using a cardiotoxin-induced mouse muscle injury model demonstrated calcium channels play important roles in the regeneration of muscle tissue, possibly by promoting the differentiation of muscle stem cells (MSCs). Summarizing, the study demonstrates ECM components secreted by myoblasts during differentiation provide an essential environment for muscle differentiation and regeneration. [ABSTRACT FROM AUTHOR]

Calcium-activated potassium (KCa) channels are ubiquitously expressed throughout the body and are able to regulate membrane potential and intracellular calcium concentrations, thereby playing key roles in cellular physiology and signal transmission. Consequently, it is unsurprising that KCa channels have been implicated in various diseases, making them potential targets for pharmaceutical interventions. Over the past two decades, numerous studies have been conducted to develop KCa channel-targeting drugs, including those for disorders of the central and peripheral nervous, cardiovascular, and urinary systems and for cancer. In this review, we synthesize recent findings regarding the structure and activating mechanisms of KCa channels. We also discuss the role of KCa channel modulators in therapeutic medicine. Finally, we identify the major reasons behind the delay in bringing these modulators to the pharmaceutical market and propose new strategies to promote their application. [ABSTRACT FROM AUTHOR]

Proanthocyanidins (PACs) find wide applications for human use including food, cosmetics, dietary supplements, and pharmaceuticals. The chemical complexity associated with PACs has triggered the development of various chromatographic techniques, with countercurrent separation (CCS) gaining in popularity. This study applied the recently developed DESIGNER (Depletion and Enrichment of Select Ingredients Generating Normalized Extract Resources) approach for the selective enrichment of trimeric and tetrameric PACs using centrifugal partition chromatography (CPC). This CPC method aims at developing PAC based biomaterials, particularly for their application in restoring and repairing dental hard tissue. A general separation scheme beginning with the depletion of polymeric PACs, followed by the removal of monomeric flavan-3-ols and a final enrichment step produced PAC trimer and tetramer enriched fractions. A successful application of this separation scheme is demonstrated for four polyphenol rich plant sources: grape seeds, pine bark, cinnamon bark, and cocoa seeds. Minor modifications to the generic DESIGNER CCS method were sufficient to accommodate the varying chemical complexities of the individual source materials. The step-wise enrichment of PAC trimers and tetramers was monitored using normal phase TLC and Diol-HPLC-UV analyses. CPC proved to be a reliable tool for the selective enrichment of medium size oligomeric PACs (OPACs). This method plays a key role in the development of dental biomaterials considering its reliability and reproducibility, as well as its scale-up capabilities for possible larger-scale manufacturing. [ABSTRACT FROM AUTHOR]

Context:Spirodela polyrhiza(L.) Schleid. (Lemnaceae), Spirodelae Herba (SH), has been known to relieve inflammation, urticaria and skin symptoms including pruritus, eczema and rash. Objective:The effects of SH extract on two calcium ion channels, Orai1 and TRPV3, and their potential as novel therapeutics for atopic dermatitis (AD) were investigated. The regulatory role of Orai1 on mast cell degranulation was evaluated. Materials and methods:The dried leaves of SH were extracted by 70% methanol. Effects of SH extract (100 μg/mL) in an HEK293T cell line overexpressing human Orai1 or TRPV3 were assessed. Ion channel modulation in transfected HEK293T cells was measured using a conventional whole-cell patch-clamp technique. IgE-antigen complex-stimulated mast cell degranulation was measured by β-hexosaminidase assay with morphological observation after treatment with 20, 50 and 100 μg/mL SH extract. Results:SH extract (100 μg/mL) significantly inhibited Orai1 activity (63.8 ± 0.97%) in Orai1-STIM1 co-overexpressed HEK293T cells. SH extract significantly increased TRPV3 activity (81.29 ± 0.05% at −100 mV) compared with the positive control 2-APB (100 μM), which induced full activation. SH extract inhibited degranulation in IgE-antigen complex-stimulated RBL-2H3 mast cells by decreasing β-hexosaminidase activity (3.14 ± 0.03, 2.56 ± 0.12 and 2.29 ± 0.08 mU/mg, respectively). Conclusion:Our results suggested that SH extract could treat abnormal skin barrier pathologies in AD through modulation of the activities of the calcium ion channels Orai1 and TRPV3 and inhibition of mast cell degranulation. This is the first report of an herbal effect on the modulation of ion channels associated with skin barrier disruption in AD pathogenesis. [ABSTRACT FROM PUBLISHER]

Background: Previously proposed criteria for preoperatively identifying endometrial cancer patients at low risk for lymph node metastasis remain to be verified. For this purpose, a prospective, multicenter observational study was performed.Methods: Eligible patients with histologically confirmed endometrial cancer underwent magnetic resonance imaging (MRI) and serum cancer antigen 125 (CA 125) testing before surgery. The following criteria were used to identify low-risk patients: 1) endometrioid-type cancer, 2) no evidence of deep myometrial invasion on MRI, 3) no enlarged lymph nodes on MRI, 4) no suspicious metastasis out of the uterine corpus, and 5) serum CA 125 levels less than 35 U/mL. Systematic pelvic and/or para-aortic lymphadenectomy was performed for all patients. The primary endpoint was estimation of the negative predictive value (NPV).Results: From January 2012 to December 2014, 529 patients from 20 hospitals in 3 Asian countries were consecutively enrolled. According to our criteria, 272 patients (51.4%) were categorized into the low-risk group. Fifty-three of the 529 patients (10.0%) had lymph node metastases; these patients included 8 (2.9%) falsely categorized as low-risk. The sensitivity and specificity of the criteria were 84.9% and 55.5%, respectively. The NPV of 97.1% was higher than the predefined target endpoint of 96%.Conclusions: The low-risk criteria based on preoperative tests were confirmed to be reliable and accurate for identifying patients at low risk for lymph node metastasis. These criteria may facilitate patient counseling and surgical decision making. Cancer 2017;123:263-272. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background Ultraviolet radiation exposure is the most important cause of extrinsic skin aging (photoaging), which causes skin wrinkling and hyperpigmentation. Although many factors are involved in the photoaging process, calcium release-activated calcium channel protein 1 (ORAI1) has been reported to be involved in UV-induced melanogenesis. Objective The aim of the present study was to find inhibitory effects of the extract of Foeniculum vulgare (fennel) fruits on ORAI1 ion channels and UV-induced melanogenesis in melanoma cells and to identify its active constituents. Methods Active compounds were isolated and quantitatively analyzed. An electrophysiological assay was performed by using the whole-cell patch-clamp technique. Intracellular free calcium concentration was measured by Fura-2. Tyrosinase activity was evaluated by levodopa colorimetry. Effects of the most active compound on cell viability of murine B16F10 melanoma cells and inhibition of melanin content after UVB irradiation were determined. Results F. vulgare fruits extract and its hexane fraction strongly blocked ORAI1 currents and tyrosinase activity and significantly inhibited UV-induced melanogenesis. Of the 13 compounds isolated from the hexane fraction, trans -anethole (TA) exhibited inhibitory effects on ORAI1 (IC 50 = 8.954 ± 1.36 μM) and increased cytoplasmic Ca 2+ concentrations in response. TA inhibited UV-induced melanogenesis without affecting tyrosinase activity. Conclusion Our findings suggest that the fruits extract of F. vulgare and its active constituent, TA, provide a possible novel approach for treating and preventing UV-induced melanogenesis. [ABSTRACT FROM AUTHOR]

Background: Quercetin regulates gastrointestinal (GI) motor activity but the molecular mechanism involved has not been determined. The authors investigated the effects of quercetin, a flavonoid present in various foods, on the pacemaker activities of interstitial cells of Cajal (ICCs) in murine small intestine in vitro and on GI motility in vivo. Materials and Methods: Enzymatic digestion was used to dissociate ICCs from mouse small intestines. The whole-cell patch-clamp configuration was used to record pacemaker potentials in cultured ICCs in the absence or presence of quercetin and to record membrane currents of transient receptor potential melastatin (TRPM) 7 or transmembrane protein 16A (Tmem16A, anoctamin1 (ANO1)) overexpressed in human embryonic kidney (HEK) 293 cells. The in vivo effects of quercetin on GI motility were investigated by measuring the intestinal transit rates (ITRs) of Evans blue in normal mice. Results: Quercetin (100-200 μM) decreased the amplitudes and frequencies of pacemaker activity in a concentration-dependent manner in current clamp mode, but this action was blocked by naloxone (a pan-opioid receptor antagonist) and by GDPβS (a GTP-binding protein inhibitor). However, potassium channels were not involved in these inhibitory effects of quercetin. To study the quercetin signaling pathway, we examined the effects of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of guanylate cyclase, and of RP-8-CPT-cGMPS, an inhibitor of protein kinase G (PKG). These inhibitors blocked the inhibitory effects of quercetin on pacemaker activities. Also, L-NAME (100 μM), a non-selective NO synthase (NOS) inhibitor, blocked the effects of quercetin on pacemaker activity and quercetin stimulated cGMP production. Furthermore, quercetin inhibited both Ca2+-activated Cl- channels (TMEM16A, ANO1) and TRPM7 channels. In vivo, quercetin (10-100 mg/kg, p.o.) decreased ITRs in normal mice in a dose-dependent manner. Conclusions: Quercetin inhibited ICC pacemaker activities by inhibiting TRPM7 and ANO1 via opioid receptor signaling pathways in cultured murine ICCs. The study shows quercetin attenuates GI tract motility, and suggests quercetin be considered the basis for the development of novel spasmolytic agents for the prevention or alleviation of GI motility dysfunctions. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Energy and cost effective pretreatment of seawater is essential for any desalination plant to convert seawater into clean water successfully. This study shows a way to pretreat seawater without excessive input of electrical energy or high pressure; it uses a bioelectrochemical cell with two chambers, divided by an anion exchange membrane (AEM). When bacteria attached on the anode produce current using organic matter as a source of fuel, hydroxyl ions can be generated in the cathode chamber, which can increase the alkalinity of the catholyte (seawater); scale-forming ions such as Ca 2 + and Mg 2 + in seawater can be removed by forming precipitates in the cathode chamber. Our results show that 84% of Ca 2 + and 37% of Mg 2 + in seawater can be effectively removed while treating wastewater in the anode chamber. These results indicate a new method to pretreat seawater without external energy input since the cell accomplishes selective removal of divalent cations using an electrochemical cathode reaction. This study provides evidence that this new method can be a viable option for membrane based seawater pretreatment and desalination processes to significantly mitigate scale problems of membranes. [ABSTRACT FROM AUTHOR]

Grape seeds are a rich source of polyphenols, especially proanthocyanidins (PACs), and are also known for the presence of galloylated oligomeric PACs (OPACs). The present study focuses on the phytochemical methodology for grape seed (O)PACs and their potential role as dentin biomodifiers to be used in restorative and reparative dentistry. A new method using centrifugal partition chromatography (CPC) was developed for the preparative separation of the grape seed (O)PACs. Orthogonal phytochemical profiling of the resulting CPC fractions was performed using C18 and diol HPLC, normal phase HPTLC, and IT-TOF MS analysis. A galloylated procyanidin dimer ( 1 ) was isolated from a CPC fraction in order to evaluate its potential to enhance dentin bio-mechanical properties. Moreover, it helped to evaluate the impact of the galloyl moiety on the observed bioactivity. Structure elucidation was performed using ESI-MS, 1D and 2D NMR analyses. For the first time, 1 H iterative full spin analysis (HiFSA) was performed on this type of molecule, enabling a detailed proton chemical shift and coupling constant assignment. The CPC fractions as well as 1 showed promising results in the dentin stiffness bioassay and indicate that they may be used as dental intervention biomaterial. [ABSTRACT FROM AUTHOR]

Cellulose fermentation wastewaters (FWWs) contain short chain volatile fatty acids and alcohols, but they also have high concentrations of proteins. Hydrogen gas production from FWW was examined using continuous flow microbial electrolysis cells (MECs), with a focus on fate of the protein. H 2 production rates were 0.49 ± 0.05 m 3 /m 3 -d for the FWW, compared to 0.63 ± 0.02 m 3 /m 3 -d using a synthetic wastewater containing only acetate (applied potential of 0.9 V). Total organic matter removal was 76 ± 6% for the FWW, compared to 87 ± 5% for acetate. The MEC effluent became relatively enriched in protein (69%) compared to that in the original FWW (19%). Protein was completely removed using higher applied voltages (1.0 or 1.2 V), but current generation was erratic due to more positive anode potentials (−113 ± 38 mV, E ap = 1.2 V; −338 ± 38 mV, 1.0 V; −0.426 ± 4 mV, 0.9 V). Bacteria on the anodes with FWW were primarily Deltaproteobacteria , while Archaea were predominantly Methanobacterium . [ABSTRACT FROM AUTHOR]

Background/Aims: Ginseng regulates gastrointestinal (GI) motor activity but the underlying components and molecular mechanisms are unknown. We investigated the effect of gintonin, a novel ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, on the pacemaker activity of the interstitial cells of Cajal (ICC) in murine small intestine and GI motility. Materials and Methods: Enzymatic digestion was used to dissociate ICC from mouse small intestines. The whole-cell patch-clamp configuration was used to record pacemaker potentials and currents from cultured ICC in the absence or presence of gintonin. In vivo effects of gintonin on gastrointestinal (GI) motility were investigated by measuring the intestinal transit rate (ITR) of Evans blue in normal and streptozotocin (STZ)-induced diabetic mice. Results: We investigated the effects of gintonin on pacemaker potentials and currents in cultured ICC from mouse small intestine. Gintonin caused membrane depolarization in current clamp mode but this action was blocked by Ki16425, an LPA1/3 receptor antagonist, and by the addition of GDPβS, a GTP-binding protein inhibitor, into the ICC. To study the gintonin signaling pathway, we examined the effects of U-73122, an active PLC inhibitor, and chelerythrine and calphostin, which inhibit PKC. All inhibitors blocked gintonin actions on pacemaker potentials, but not completely. Gintonin-mediated depolarization was lower in Ca2+-free than in Ca2+-containing external solutions and was blocked by thapsigargin. We found that, in ICC, gintonin also activated Ca2+-activated Cl- channels (TMEM16A, ANO1), but not TRPM7 channels. In vivo, gintonin (10-100 mg/kg, p.o.) not only significantly increased the ITR in normal mice but also ameliorated STZ-induced diabetic GI motility retardation in a dose-dependent manner. Conclusions: Gintonin-mediated membrane depolarization of pacemaker activity and ANO1 activation are coupled to the stimulation of GI contractility through LPA1/3 receptor signaling pathways in cultured murine ICC. Gintonin might be a ingredient responsible for ginseng-mediated GI tract modulations, and could be a novel candidate for development as a prokinetic agent that may prevent or alleviate GI motility dysfunctions in human patients. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: A novel biological activity of psoralidin as an agonist for both estrogen receptor (ER)α and ERβ agonist has been demonstrated in our study. Psoralidin has been characterized as a full ER agonist, which activates the classical ER-signaling pathway in both ER-positive human breast and endometrial cell lines as well as non-human cultured cells transiently expressing either ERα or ERβ. The estrogenic activity was determined using the relative expression levels of either reporter or the endogenous genes dependent on the agonist-bound ER to the estrogen response element (ERE). Psoralidin at 10μM was able to induce the maximum reporter gene expression corresponding to that of E2-treated cells and such activation of the ERE-reporter gene by psoralidin was completely abolished by the cotreatment of a pure ER antagonist, implying that the biological activities of psoralidin are mediated by ER. Psoralidin was also able to induce the endogenous estrogen-responsive gene, pS2, in human breast cancer cells MCF-7. It was observed that activation of the classical ER-signaling pathway by psoralidin is mediated via induction of ER conformation by psoralidin and direct binding of the psoralidin–ER complex to the EREs present in the promoter region of estrogen-responsive genes, as shown by chromatin immunoprecipitation assay results. Finally, molecular docking of psoralidin to the ligand binding pocket of the ERα showed that psoralidin is able to mimic the binding interactions of E2, and thus, it could act as an ER agonist in the cellular environment. [Copyright &y& Elsevier]

Phytochemical investigation of the seeds of Alpinia katsumadai (Zingiberaceae) led to the isolation and identification of six new diarylheptanoid derivatives, katsumains D-G ( 1- 4), 3-(acetyloxy)-alpinikatin ( 5), and 5-(acetyloxy)alpinikatin ( 6). The structures of 1- 6 were elucidated by spectroscopic data analysis including 1D- and 2D-NMR experiments. [ABSTRACT FROM AUTHOR]

Background/Aims: To discuss the latest findings on oncologic and reproductive outcomes of fertility-sparing surgery in epithelial ovarian cancer (EOC) and to suggest proper indications for this treatment. Methods: A search of Medline database was performed for articles dealing with fertility-sparing surgery for EOC published in the English literature between January 1, 1969, and October 1, 2012. Results: To date, 918 patients with EOC underwent fertility-sparing surgery; 109 (11.9%) had disease recurrence and 48 (5.2%) died of disease. Retrospective studies suggest that fertility-sparing surgery may be safely performed in young women with a strong desire to preserve fertility and with nonclear cell histology, FIGO stage IA, IC and grade 1-2 disease or clear cell histology and FIGO stage IA disease. To date, 177 patients have succeeded in achieving 242 pregnancies, resulting in 214 term (88%) and 1 preterm (0.4%) births. Miscarriage rate was about 10% (25/242) and ectopic pregnancy rate was 0.8% (2/242) after fertility-sparing surgery. No congenital anomaly has been reported. Conclusions: Although randomized controlled trials have yet to be performed, many studies have suggested that fertility-sparing surgery is safe, with promising reproductive outcomes. Cautious selection of patients is important because of 5.2% mortality and 11% recurrence after this surgery. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Highlights: [•] Membrane stack configuration was optimized for the MREC utilizing NH4HCO3 solutions. [•] The optimum number of cell pairs was determined to be five. [•] Increasing the number of cell pairs did not appreciably affect anode performance. [•] Adding an LC chamber reduced ammonia crossover and improved hydrogen production. [ABSTRACT FROM AUTHOR]

Abstract: Nickel foam (NF), stainless steel wool (SSW), platinum coated stainless steel mesh (Pt), and molybdenum disulfide coated stainless steel mesh (MoS2) electrodes have been proposed as catalysts for hydrogen gas production, but previous tests have primarily examined their performance in well buffered solutions. These materials were compared using two-chamber microbial electrolysis cells (MECs), and linear sweep voltammetry (LSV) in unbuffered saline solutions at two different initial pHs (7 and 12). There was generally no appreciable effect of initial pH on production rates or total gas production. NF produced hydrogen gas at a rate of 1.1 m3 H2/m3·d, which was only slightly less than that using Pt (1.4 m3 H2/m3·d), but larger than that obtained with SSW (0.52 m3 H2/m3·d) or MoS2 (0.67 m3 H2/m3·d). Overall hydrogen gas recoveries with SSW (29.7 ± 0.5 mL), MoS2 (28.6 ± 1.3 mL) and NF (32.4 ± 2 mL) were only slightly less than that of Pt (37.9 ± 0.5 mL). Total energy recoveries, based on the gas produced versus electrical energy input, ranged from 0.75 ± 0.02 for Pt, to 0.55 ± 0.02 for SSW. An LSV analysis showed no effect of pH for NF and Pt, but overpotentials were reduced for MoS2 and SSW by using an initial lower pH. At cathode potentials more negative than −0.85 V (vs Ag/AgCl), NF had lower overpotentials than the MoS2. These results provide the first assessment of these materials under practical conditions of high pH in unbuffered saline catholytes, and position NF as the most promising inexpensive alternative to Pt. [Copyright &y& Elsevier]

Transient receptor potential melastatin 7 ( TRPM7) plays a role in a number of physiological and pharmacological functions in variety of cells. The aim of this study was to clarify the role for TRPM7 channels and the effect of waixenicin A on the pacemaking activity of interstitial cells of Cajal ( ICCs) and on the cell viability of the human gastric and breast adenocarcinoma cell lines, AGS and MCF-7, respectively. Waixenicin A decreased the amplitude of pacemaker potentials in cultured ICC clusters and inhibited TRPM7 currents, but had no effect on Ca2+-activated Cl− conductance ( ANO1). Furthermore, waixenicin A was found to inhibit the growth and survival of AGS and MCF-7 cells. These findings indicate that TRPM7 channel modulates intestinal motility and regulates the pathophysiology of human gastric and breast adenocarcinoma cells. These findings suggest that TRPM7 channel be considered a potential target for the treatment of gut motor disorders and gastric and breast cancer. [ABSTRACT FROM AUTHOR]

Abstract: c-Jun NH2-terminal kinases (JNKs) and phosphatidylinositol 3-kinase (PI3-K) play critical roles in chronic diseases such as cancer, type II diabetes, and obesity. We describe here the binding of quercetagetin (3,3′,4′,5,6,7-hydroxyflavone), related flavonoids, and SP600125 to JNK1 and PI3-K by ATP-competitive and immobilized metal ion affinity-based fluorescence polarization assays and measure the effect of quercetagetin on JNK1 and PI3-K activities. Quercetagetin attenuated the phosphorylation of c-Jun and AKT, suppressed AP-1 and NF-κB promoter activities, and also reduced cell transformation. It attenuated tumor incidence and reduced tumor volumes in a two-stage skin carcinogenesis mouse model. Our crystallographic structure determination data show that quercetagetin binds to the ATP-binding site of JNK1. Notably, the interaction between Lys55, Asp169, and Glu73 of JNK1 and the catechol moiety of quercetagetin reorients the N-terminal lobe of JNK1, thereby improving compatibility of the ligand with its binding site. The results of a theoretical docking study suggest a binding mode of PI3-K with the hydroxyl groups of the catechol moiety forming hydrogen bonds with the side chains of Asp964 and Asp841 in the p110γ catalytic subunit. These interactions could contribute to the high inhibitory activity of quercetagetin against PI3-K. Our study suggests the potential use of quercetagetin in the prevention or therapy of cancer and other chronic diseases. [Copyright &y& Elsevier]

Abstract: The hydrogen production rate in a microbial electrolysis cell (MEC) using a non-buffered saline catholyte (NaCl) can be optimized through proper control of the initial anolyte pH and catholyte NaCl concentration. The highest hydrogen yield of 3.3 ± 0.4 mol H2/mole acetate and gas production rate of 2.2 ± 0.2 m3 H2/m3/d were achieved here with an initial anolyte pH = 9 and catholyte NaCl concentration of 98 mM. Further increases in the salt concentration substantially reduced the anolyte pH to as low as 4.6, resulting in reduced MEC performance due to pH inhibition of exoelectrogens. Cathodic hydrogen recovery was high (r cat  > 90%) as hydrogen consumption by hydrogenotrophic methanogens was prevented by separating the anode and cathode chambers using a membrane. These results show that the MEC can be optimized for hydrogen production through proper choices in the concentration of a non-buffered saline catholyte and initial anolyte pH in two chamber MECs. [Copyright &y& Elsevier]

Abstract: Ca2+ influx through Ca2+-release activated Ca2+ channels (CRAC) is critical for activating immune cells. Orai and STIM proteins comprise the molecular components of CRAC. We previously observed that curcumin and caffeic acid phenethyl ester (CAPE) inhibit CRAC current in Orai1/STIM1-co-expressing HEK293 cells (Nam et al., 2009; Shin et al., 2011) [1,2]. Both compounds contain electrophilic α,β-unsaturated carbonyl groups that potentially form Michael addition with cysteine residues. We investigated the sensitivity of cysteine mutated Orai1 to curcumin and CAPE to delineate their inhibitory mechanism. Replacing the 195 cysteine residue with serine (C195S) reversed the effect of CAPE from inhibition to facilitation and significantly weakened the inhibitory effect of curcumin. Tetrahydrocurcumin, a curcumin metabolite, showed a less potent inhibitory effect on ICRAC, and this effect was abolished in C195S Orai1. Additive mutation of other cysteines (C143S and C126S) had no further influence on the effects of CAPE and curcumin. These results indicate that the electrophilic addition to the Orai1 195Cys was responsible for the inhibitory effect of ICRAC by curcumin and CAPE. [Copyright &y& Elsevier]

Abstract: SLC26A3 functions as a chloride/bicarbonate anion exchanger expressed in the secretory epithelial cells in the intestine, pancreas, and salivary glands. SLC26A3 has a C-terminal class I PDZ binding motif that assembles regulatory factors or other transporters by anchoring to various PDZ scaffold proteins. NHERF4 is an epithelial-enriched PDZ domain scaffold protein that has attracted attention because of its enriched tissue expression in the intestine and kidney. In this study, we identified SLC26A3 as a novel binding transporter of NHERF4. We investigated the functional role of NHERF4 in the regulation of SLC26A3 by using integrated biochemical and physiological approaches. A direct protein–protein interaction was identified between the PDZ-binding motif of SLC26A3 and the third PDZ domain of NHERF4. Interaction with NHERF4 decreased the level of SLC26A3 expression on the plasma membrane, which led to reduced SLC26A3 anion exchange activity. Notably, interaction with NHERF4 induced rapid internalisation of SLC26A3 from the plasma membrane. The SLC26A3–NHERF4 interaction was modulated by phosphorylation; serine 329 of NHERF4-PDZ3 played a critical role in modulating binding selectivity. Our findings suggest that NHERF4 is a novel modulator of luminal fluidity in the intestine by adjusting SLC26A3 expression and activity through a phosphorylation-dependent mechanism. [Copyright &y& Elsevier]

Extracellular enzymes offer active catalysis for hydrolysis of organic solid wastes in anaerobic digestion. To evidence the quantitative significance of hydrolytic enzyme activities for major waste components, track studies of thermophilic and mesophilic anaerobic sequencing-batch reactors (TASBR and MASBR) were conducted using a co-substrate of real organic wastes. During 1 day batch cycle, TASBR showed higher amylase activity for carbohydrate (46%), protease activity for proteins (270%), and lipase activity for lipids (19%) than MASBR. In particular, the track study of protease identified that thermophilic anaerobes degraded protein polymers much more rapidly. Results revealed that differences in enzyme activities eventually affected acidogenic and methanogenic performances. It was demonstrated that the superior nature of enzymatic capability at thermophilic condition led to successive high-rate acidogenesis and 32% higher CH 4 recovery. Consequently, these results evidence that the coupling thermophilic digestion with sequencing-batch operation is a viable option to promote enzymatic hydrolysis of organic particulates. [ABSTRACT FROM AUTHOR]

Three new flavonoids, 5,6,7,8,3′,4′-hexamethoxyhomoflavone ( 1), 5,6,7,8,4′-pentamethoxyhomoflavone ( 2) and 3,6,7,8,2′,5′-hexamethoxyflavone ( 3) were isolated from the peels of mature fruits of Citrus unshiu Marcow (Rutaceae), together with the three known compounds 6,7,8,4′-tetramethoxyflavone (=6,7,8-trimethoxy-2-(4-methoxyphenyl)-4 H-1-benzopyran-4-one), 3,5,7,8,2′,5′-hexamethoxyflavone (=2-(2,5-dimethoxyphenyl)-3,5,7,8-tetramethoxy-4 H-1-benzopyran-4-one), and scopoletin (=7-hydroxy-6-methoxy-2 H-1-benzopyran-2-one) of which the former two have never been isolated from natural resources, although they have been reported as synthetic compounds. The structures of 1- 3 were elucidated on the basis of spectroscopic evidence, including 1D- and 2D-NMR analysis. [ABSTRACT FROM AUTHOR]

Abstract: Chronic clonorchiasis, caused by direct and continuous contact with Clonorchis sinensis worms and their excretory–secretory products, is associated with hepatobiliary damage, inflammation, periductal fibrosis and even development of cholangiocarcinoma. Our previous report revealed that intracellular reactive oxygen species were generated in C. sinensis excretory–secretory product-treated human cholangiocarcinoma cells; however, their endogenous sources and pathophysiological roles in host cells were not determined. In the present study, we found that treatment of human cholangiocarcinoma cells with excretory–secretory products triggered increases in free radicals via a time-dependent activation of NADPH oxidase, xanthine oxidase and inducible nitric oxide synthase. This increase in free radicals substantially promoted the degradation of cytosolic IκB-α, nuclear translocation of nuclear factor-κB subunits (RelA and p50), and increased κB consensus DNA-binding activity. Excretory–secretory product-induced nuclear factor-κB activation was markedly attenuated by preincubation with specific inhibitors of each free radical-producing enzyme or the antioxidant, N-acetylcysteine. Moreover, excretory–secretory products induced an increase in the mRNA and protein expression of the proinflammatory cytokines, IL-1β and IL-6, in an nuclear factor-κB-dependent manner, indicating that enzymatic production of free radicals in ESP-treated cells participates in nuclear factor-κB-mediated inflammation. These findings provide new insights into the pathophysiological role of C. sinensis excretory–secretory products in host chronic inflammatory processes, which are initial events in hepatobiliary diseases. [Copyright &y& Elsevier]

Abstract: High rates of hydrogen gas production were achieved in a two chamber microbial electrolysis cell (MEC) without a catholyte phosphate buffer by using a saline catholyte solution and a cathode constructed around a stainless steel mesh current collector. Using the non-buffered salt solution (68 mM NaCl) produced the highest current density of 131 ± 12 A/m3, hydrogen yield of 3.2 ± 0.3 mol H2/mol acetate, and gas production rate of 1.6 ± 0.2 m3 H2/m3·d, compared to MECs with catholytes externally sparged with CO2 or containing a phosphate buffer. The salinity of the catholyte achieved a high solution conductivity, and therefore the electrode spacing did not appreciably affect performance. The coulombic efficiency with the cathode placed near the membrane separating the chambers was 83 ± 4%, similar to that obtained with the cathode placed more distant from the membrane (84 ± 4%). Using a carbon cloth cathode instead of the stainless steel mesh cathode did not significantly affect performance, with all reactor configurations producing similar performance in terms of total gas volume, COD removal, r cat and overall energy recovery. These results show MEC performance can be improved by using a saline catholyte without pH control. [Copyright &y& Elsevier]

Abstract: Hydrogen production in a microbial electrolysis cell (MEC) can be achieved by either setting the anode potential with a potentiostat, or by adding voltage to the circuit with a power source. In batch tests the largest total gas production (46 ± 3 mL), lowest energy input (2.3 ± 0.3 kWh/m3 of H2 generated), and best overall energy recovery (ŋE+S  = 58 ± 6%) was achieved at a set anode potential of EAn  = −0.2 V (vs Ag/AgCl), compared to set potentials of −0.4 V, 0 V and 0.2 V, or an added voltage of Eap  = 0.6 V. Gas production was 1.4 times higher with EAn  = −0.2 V than with Eap  = 0.6 V. Methane production was also reduced at set anode potentials of −0.2 V and higher than the other operating conditions. Continuous flow operation of the MECs at the optimum condition of EAn  = −0.2 V initially maintained stable hydrogen gas production, with 68% H2 and 21% CH4, but after 39 days the gas composition shifted to 55% H2 and 34% CH4. Methane production was not primarily anode-associated, as methane was reduced to low levels by placing the anode into a new MEC housing. These results suggest that MEC performance can be optimized in terms of hydrogen production rates and gas composition by setting an anode potential of −0.2 V, but that methanogen proliferation must be better controlled on non-anodic surfaces. [Copyright &y& Elsevier]

Abstract: Assessing contemporary anaerobic biotechnologies requires proofs on reliable performance in terms of renewable bioenergy recovery such as methane (CH4) production rate, CH4 yield while removing volatile solid (VS) effectively. This study, therefore, aims to evaluate temperature-phased anaerobic sequencing batch reactor (TPASBR) system that is a promising approach for the sustainable treatment of organic fraction of municipal solid wastes (OFMSW). TPASBR system is compared with a conventional system, mesophilic two-stage anaerobic sequencing batch reactor system, which differs in operating temperature of 1st-stage. Results demonstrate that TPASBR system can obtain 44% VS removal from co-substrate of sewage sludge and food waste while producing 1.2m3CH4/m3 system/d (0.2m3CH4/kgVSadded) at organic loading rate of 6.1gVS/L/d through the synergy of sequencing-batch operation, co-digestion, and temperature-phasing. Consequently, the rapid and balanced anaerobic metabolism at thermophilic stage makes TPASBR system to afford high organic loading rate showing superior performance on OFMSW stabilization. [Copyright &y& Elsevier]

Abstract: Here, we report that a continuous single-chamber microbial fuel cell (MFC) is applicable to wastewaters containing a high nitrogen concentration using a process of adaptation. Continuous experiments are conducted to investigate the inhibitory effect of total ammonia nitrogen (TAN) on the MFC using influents with various concentrations of TAN ranged from 84 to 10,000mgNL−1. As the TAN concentration increases up to 3500mgNL−1, the maximum power density remains at 6.1Wm−3. However, as the concentration further increases, TAN significantly inhibits the maximum power density, which is reduced at saturation to 1.4Wm−3 at 10,000mgNL−1. We confirm that the adapted electrical performance of a continuous MFC can generate approximately 44% higher power density than the conductivity control. A comparative study reveals that the power densities obtained from a continuous MFC can sustain 7-fold higher TAN concentration than that of previous batch MFCs. TAN removal efficiencies are limited to less than 10%, whereas acetate removal efficiencies remain as high as 93–99%. The increased threshold TAN of the continuous MFC suggests that microbial acclimation in a continuous MFC can allow the electrochemical functioning of the anode-attached bacteria to resist ammonia inhibition. [Copyright &y& Elsevier]

Myricetin is a widely distributed flavonol that is found in many plants, including tea, berries, fruits, vegetables, and medicinal herbs. Abundant sources provide interesting insights into the multiple mechanisms by which myricetin mediates chemopreventive effects on skin cancer. Myricetin strongly inhibited tumor promoter-induced neoplastic cell transformation by inhibiting MEK, JAK1, Akt, and MKK4 kinase activity directly. In a mouse skin model, myricetin attenuated the ultraviolet B (UVB)-induced COX-2 expression and skin tumor formation by regulating Fyn. Myricetin-mediated inactivation of Akt in the UVB response plays a role in regulating UVB-induced carcinogenesis. Recently, myricetin was found to inhibit UVB-induced angiogenesis by targeting PI3-K in an SKH-1 hairless mouse skin tumorigenesis model. Raf kinase is a critical target for myricetin in inhibiting the UVB-induced formation of wrinkles and suppression of type I procollagen and collagen levels in mouse skin. Accumulated data suggest that myricetin acts as a promising agent for the chemoprevention of skin cancer. [ABSTRACT FROM AUTHOR]

Epidemiological studies suggest that coffee consumption reduces the risk of cancers, including colon cancer, but the molecular mechanisms and target(s) underlying the chemopreventive effects of coffee and its active ingredient(s) remain unknown. Based on serving size or daily units, coffee contains larger amounts of phenolic phytochemicals than tea or red wine. Coffee or chlorogenic acid inhibited CT-26 colon cancer cell-induced lung metastasis by blocking phosphorylation of ERKs. Coffee or caffeic acid (CaA) strongly suppressed mitogen-activated MEK1 and TOPK activities and bound directly to either MEK1 or TOPK in an ATP-noncompetitive manner. Coffee or CaA, but not caffeine, inhibited ERKs phosphorylation, AP-1 and NF-κB transactivation and subsequently inhibited TPA-, EGF- and H-Ras-induced neoplastic transformation of JB6 P+ cells. Coffee consumption was also associated with a significant attenuation of ERKs phosphorylation in colon cancer patients. These results suggest that coffee and CaA target MEK1 and TOPK to suppress colon cancer metastasis and neoplastic cell transformation. [ABSTRACT FROM AUTHOR]

Abstract: Multiple lines of evidences suggest that oxidative stress induced by reactive oxygen species are closely related to multi-stage carcinogenesis. Polyphenols, a group of chemicals with more than one phenol unit or building block per molecule, have been recognized for possessing many health benefits including cancer-preventive effects mainly due to their antioxidant activity. However, polyphenols can directly bind with signaling molecules involved in carcinogenesis and regulate its activity. Moreover, it is noteworthy that the binding between the polyphenol and the target protein is determined by their structural relationship, which implies that different polyphenols have different target proteins, leading to divergent chemopreventive effects. Extracellular stimuli transmit signals into a cell by activating their target signaling cascades involved in carcinogenesis. As an example, Src family kinase, a family of proto-oncogenic tyrosine kinases activated by a variety of oxidative stress and proinflammatory agents, is known to regulate cell proliferation, differentiation, survival and angiogenesis. Src family kinase subsequently activates downstream signal cascades including mitogen-activated protein kinase, phosphoinositol-3-kinase, and nuclear factor-kappaB, thereby inducing cell proliferation and causing cancer. Recent studies demonstrate that polyphenols can directly target signaling cascades involved in inflammation and the development of cancer. Inhibition of the kinases by polyphenols contributes to the attenuation of carcinogenesis. Therefore, the development of polyphenols as direct inhibitors against target proteins is regarded as a rational approach for chemoprevention. This review describes and discusses recent results about the direct interactions of polyphenols and protein kinases in cancer chemoprevention. [Copyright &y& Elsevier]

Abstract: Batch experiments are conducted at various concentrations of initial total ammonia nitrogen (TAN) with acetate as an electron donor to examine the effects of free ammonia (NH3) inhibition on electricity production in single-chambered microbial fuel cells (MFCs). This research demonstrates that initial TAN concentrations of over 500mgNL−1 significantly inhibit electricity generation in MFCs. The maximum power density of 4240mWm−3 at 500mgNL−1 drastically decreases to 1700mWm−3 as the initial TAN increases up to 4000mgNL−1. Nitrite and nitrate analysis confirms that nitrification after complete acetate removal consumes some TAN. Ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) are also inhibited by increasing the initial TAN concentrations. Another batch experiment verifies the strong inhibitory effect of TAN with only small differences between the half-maximum effective concentration (EC50) for TAN (894mgNL−1 equivalent to 10mgNL−1 as NH3) and optimum TAN conditions; it requires careful monitoring of the TAN for MFCs. In addition, abiotic control experiments reveal that granular activated carbon, which is used as an auxiliary anode material, adsorbs a significant amount of ammonia at each TAN concentration in batch MFCs. [Copyright &y& Elsevier]

Abstract: Cocoa, a good source of dietary antioxidative polyphenols, exhibited anticarcinogenic activity in animal models, but the molecular mechanisms of the chemopreventive potential of cocoa remain unclear. Inhibition of gap-junction intercellular communication (GJIC) is strongly related to tumorigenesis. Cocoa polyphenol extracts (CPE) dose dependently attenuated hydrogen peroxide (H2O2)-induced inhibition of GJIC in rat liver epithelial (RLE) cells. CPE inhibited the H2O2-induced phosphorylation and internalization of connexin 43, which is a regulating protein of GJIC in RLE cells. The H2O2-induced accumulation of reactive oxygen species and activation of extracellular signal-regulated kinase were inhibited by CPE treatment. However, CPE did not block H2O2-induced phosphorylation of p38 mitogen-activated protein kinase. An ex vivo kinase assay demonstrated that CPE inhibited the H2O2-induced mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) 1 activity in RLE cell lysates. Ex vivo pull-down assay data revealed that CPE directly bound with MEK1 to inhibit MEK1 activity. These results indicate that CPE protects against the H2O2-induced inhibition of GJIC through antioxidant activity and direct inhibition of MEK activity, which may contribute to its chemopreventive potential. [Copyright &y& Elsevier]

Abstract: Microbial fuel cells (MFCs) are operated with solutions containing various chemical species required for the growth of electrochemically active microorganisms including nutrients and vitamins, substrates, and chemical buffers. Many different buffers are used in laboratory media, but the effects of these buffers and their inherent electrolyte conductivities have not been examined relative to current generation in MFCs. We investigated the effect of several common buffers (phosphate, MES, HEPES, and PIPES) on power production in single chambered MFCs compared to a non-buffered control. At the same concentrations the buffers produced different solution conductivities which resulted in different ohmic resistances and power densities. Increasing the solution conductivities to the same values using NaCl produced comparable power densities for all buffers. Very large increases in conductivity resulted in a rapid voltage drop at high current densities. Our results suggest that solution conductivity at a specific pH for each buffer is more important in MFC studies than the buffer itself given relatively constant pH conditions. Based on our analysis of internal resistance and a set neutral pH, phosphate and PIPES are the most useful buffers of those examined here because pH was maintained close to the pK a of the buffer, maximizing the ability of the buffer to contribute to increase current generation at high power densities. [Copyright &y& Elsevier]

Abstract: Several sesquiterpene lactones that have been isolated from medicinal plants are known to have many pharmacological activities. In this study, we investigated the anti-inflammatory effects of zedoarondiol, a sesquiterpene lactone isolated from the rhizoma of Curcuma heyneana, in lipopolysaccharide (LPS)-stimulated macrophage cells. Zedoarondiol dose-dependently inhibited LPS-stimulated nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) productions in RAW 264.7 macrophage and in mouse peritoneal macrophage cells. Consistent with these findings, in RAW 264.7 cells, zedoarondiol suppressed the LPS-stimulated protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and the mRNA expressions of iNOS, COX-2, TNF-α, IL-6, and IL-1β in a concentration-dependent manner. Moreover, molecular data revealed that zedoarondiol inhibited LPS-stimulated DNA binding activity and the transcription activity of nuclear factor-kappa B (NF-κB), and this effect was accompanied by decreases in the degradation and phosphorylation of inhibitory κB (IκB)-α, and in the subsequent blocking of NF-κB translocations to the nucleus. Furthermore, zedoarondiol attenuated the phosphorylations of IκB kinase (IKK), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38), and c-Jun N-terminal kinase (JNK) in LPS-stimulated RAW 264.7 cells. Taken together, the findings of the present study indicate that zedoarondiol inhibits iNOS, COX-2, and pro-inflammatory cytokine expressions by suppressing the phosphorylations of IKK and MAPKs, and by subsequently inactivating the NF-κB pathway. These relations reveal, in part, the mechanism underlying the anti-inflammatory properties of zedoarondiol. [Copyright &y& Elsevier]