ObjectiveThe cost-effectiveness of antiviral treatment in adult immune-tolerant (IT) phase chronic hepatitis B (CHB) patients is uncertain.DesignWe designed a Markov model to compare expected costs and quality-adjusted life-years (QALYs) of starting antiviral treatment at IT-phase (‘treat-IT’) vs delaying the therapy until active hepatitis phase (‘untreat-IT’) in CHB patients over a 20-year horizon. A cohort of 10 000 non-cirrhotic 35-year-old patients in IT-phase CHB (hepatitis B e antigen-positive, mean serum hepatitis B virus (HBV) DNA levels 7.6 log10 IU/mL, and normal alanine aminotransferase levels) was simulated. Input parameters were obtained from previous studies at Asan Medical Center, Korea. The incremental cost-effectiveness ratio (ICER) between the treat-IT and untreat-IT strategies was calculated.ResultsFrom a healthcare system perspective, the treat-IT strategy with entecavir or tenofovir had an ICER of US$16 516/QALY, with an annual hepatocellular carcinoma (HCC) incidence of 0.73% in the untreat-IT group. With the annual HCC risk ≥0.54%, the treat-IT strategy was cost-effective at a willingness-to-pay threshold of US$20 000/QALY. From a societal perspective considering productivity loss by premature death, the treat-IT strategy was extremely cost-effective, and was dominant (ICER <0) if the HCC risk was ≥0.43%, suggesting that the treat-IT strategy incurs less costs than the untreat-IT strategy. The most influential parameters on cost-effectiveness of the treat-IT strategy were those related with HCC risk (HBV DNA levels, platelet counts and age) and drug cost.ConclusionStarting antiviral therapy in IT phase is cost-effective compared with delaying the treatment until the active hepatitis phase in CHB patients, especially with increasing HCC risk, decreasing drug costs and consideration of productivity loss.

This study determined the effects of blueberry fermentation by Lactobacillus plantarum on antioxidant and anticancer activities. The fermented blueberries extracted with 80% ethanol (FBE) showed increased superoxide dismutase‐like activity, increased scavenging of DPPH and alkyl radicals, and increased antiproliferative activity against human cervical carcinoma HeLa cells by inducing apoptosis. Seven representative phenolic compounds (malvidin 3‐O‐glucopyranoside, gallic acid, protocatechuic acid, catechol, chlorogenic acid, syringic acid, and epigallocatechin) in FBE were measured by high‐performance liquid chromatography at different fermentation times. The content of each phenolic compound in the FBE was dependent on the fermentation period. Protocatechuic acid and catechol levels increased significantly with fermentation time. Of these three major compounds (protocatechuic acid, catechol, and chlorogenic acid), catechol showed the most significant anticancer activity when HeLa cells were treated with each of these three compounds alone or mixed in various ratios. Pearson's product‐moment correlation analysis revealed that the increases in antioxidant and anticancer activities following blueberry fermentation were positively correlated with the phenolic acids present in FBE. Practical Application Blueberries fermented with a tannase‐producing lactic acid bacteria (LAB), Lactobacillus plantarum showed higher antioxidant activities and antiproliferative activities against human cervical carcinoma HeLa cells than did raw blueberries. L. plantarum fermentation biotransformed blueberry polyphenols into active phenol metabolites with strong antioxidant and antiproliferative activities. Our results suggest that fermented blueberries are rich in phenolic acids, which are a promising source of natural antioxidants and anticancer drugs and can be used as additives in food, pharmaceuticals, and cosmetic preparations.

Myricetin is a commonly found dietary flavonoid. In the present study, we investigated the effects of myricetin on migration and invasion of radioresistant lung cancer cells (A549‐IR). Transcriptome analysis of A549‐IR cells identified several differentially expressed genes (DEGs) in A549‐IR cells compared to parental A549 cells. Functional enrichment analysis revealed that most of the DEGs were linked with PI3K‐AKT signaling, proteoglycans, focal adhesion, and ECM–receptor interactions. A549‐IR cells demonstrated enhanced migratory potential with increased expression of vimentin, snail and slug, and reduced expression of E‐cadherin. A549‐IR cells exposed to myricetin displayed reduced migration and suppressed MMP‐2 and MMP‐9 expression. Notably, myricetin inhibited the phosphorylation of focal adhesion kinase (FAK) and altered the F‐actin/G‐actin ratio in A549‐IR cells, without modulation of EMT markers. These findings suggest that myricetin can inhibit migration of A549‐IR cells by suppressing MMP‐2 and MMP‐9 expressions through inhibition of the FAK‐ERK signaling pathway.

Background Annona squamosa L. is a branched shrub, which is believed to be originated from the America and West Indies. Fruits of this plant are commonly known as custard apple, sugar apple, or sweetsops. A number of studies have proven a range of biological activities associated with various parts of A. squamosa. Aims The main aim of the present investigation was to evaluate potential inhibitory effects of A. squamosa leaf extract (ALE) on melanogenesis and its underlying mechanisms in B16F10 murine melanoma cells. Methods Inhibitory effects of A. squamosa leaf extract (ALE) on melanogenesis were primarily assessed by determining melanin contents. Effects of ALE on tyrosinase activity and the expression of proteins associated with melanogenesis were then determined. GC–MS analysis was carried out to identify the phytochemical profile of A. squamosa leaf extract. Results Antimelanogenic effects of ALE were found to exert through the inhibition of melanocyte inducing transcription factor (MITF) and activation of p38. GC‐MS analysis identified ent‐kaur‐16‐en‐19‐ol, 18‐oxokauran‐17‐yl acetate, and β‐sitosterol as major phytochemicals. Conclusion To our knowledge, this is the first study on the antimelanogenic effects of A. squamosa leaves, rationalizing the use A. squamosa leaf extract as a natural depigmentation agent for the treatment of skin diseases and the development of cosmetic products with enhanced skin‐lightening capabilities.

Compositions of essential oils extracted from mint herb such as Mentha piperita, Mentha spicata, and Mentha × piperita var. citrate produced in Jeju were analyzed using gas chromatography-mass spectrometry (GC-MS) and headspace-GC-MS (HS-GC-MS). By the GC-MS analysis, 13 compounds were tentatively identified in Mentha piperita, Mentha spicata, and Mentha × piperita var. citrate, respectively. Peperitenone oxide, carvone, and linalool were detected as major compounds in Mentha piperita, in Mentha spicata, in Mentha × piperita var. citrate, respectively, based on the ratio of peak intensity in the total ion chromatogram. The greater number of compounds, including volatile alcohols and acetates were identified by HS-GC-MS than by GC-MS in these all three essential oils. Similar patterns of composition were detected in both Mentha spicata and Mentha × piperita var. citrate by either one of GC-MS methods. However, in case of Mentha piperita, L-(−)-menthol, which was identified as the major compound by HS-GC-MS was detected in dramatically reduced quantity by GC-MS. Interestingly, we found that both linalyl acetate and linalool were identified as the dominant compounds in the essential oil of Mentha × piperita var. citrate.

Little information about the biological activities of Citrus limon (lemon) leaves has been reported, whereas the fruit of Citrus limon (lemon) has been well-documented to contain various pro-health bio-functional compounds. In the present study, the antiproliferative activities of the lemon leaves were evaluated using several cancer cell lines. From the n-hexane, chloroform, ethyl acetate, n-butanol, and water fractions of methanolic extract of the leaves, the chloroform fraction of lemon leaves (CFLL) showed the most potent antiproliferative activity in the AGS human gastric cancer cells. The current study demonstrates that CFLL induces apoptosis in AGS cells, as evidenced by an increase in apoptotic bodies, cell population in the sub-G1 phase, Bax/Bcl-2 ratio, and cleavage of poly (ADP-ribose) polymerase (PARP), caspase-3 and caspase-9. Compositional analysis of the CFLL using gas chromatography mass spectrometry (GC-MS) resulted in the identification of 27 compounds including trans, trans-farnesol (3.19 %), farnesol (3.26 %), vanillic acid (1.45 %), (−)-loliolide (5.24 %) and palmitic acid (6.96 %). Understanding the modes of action of these compounds individually and/or synergistically would provide useful information about their applications in cancer prevention and therapy.

Five extraction conditions (AE, autoclave extraction; OE, oven extraction; HWSE, hot water and sonication extraction; HWASE, hot water acidified with 0.5% (v/v) acetic acid and sonication extraction; and BE, boiling extraction) were examined to compare the effects of different hot water extraction methods on the antioxidant properties of blueberries. The extraction yields of the AE, OE, HWSE, HWASE, and BE were 7.94%, 8.35%, 8.55% 9.15%, and 8.50%, respectively. The polyphenol and flavonoid contents of AE were 3.47 mg GAE/g and 1.59 mg RE/g, respectively, which were highest centents among others. Those of OE were ranked second to the highest. The total anthocyanin content of HWSE (5.29 mg/g) was significantly higher than that of others whereas that of AE showed the lowest content (0.96 mg/g). The order of ABTS radical and alkyl radical scavenging activities was as follows: AE > BE > OE > HWSE > HWASE. The antioxidant properties were considerably correspondent with the total polyphenol and flavonoid content. DPPH radical scavenging activity was quite high in HWSE, AE, and BE extraction, however, there were no significant differences among the five extraction methods in the aspect of Fe2+ ion chelating activities. Moreover, AE showed the highest SOD activity, and protected the dermal fibroblast the best against H2O2-induced cytotoxicity. In conclusion, it was suggested that the autoclave extraction (AE) would be the most effective method for preparing blueberry hot water extracts with relatively high antioxidant activities.

In this study, antioxidant activities and physicochemical properties of chocolate fermented with Lactobacillus plantarum CK10 were investigated. The pH level decreased from 5.26±0.02 to 3.98±0.06 during fermentation while titratable acidity increased from 5.36±0.19 to 13.31±0.34. The total polyphenol and flavonoid contents slightly increased during fermentation, but it was numerically negligible. Slight increase and decrease in the radical scavenging activities of chocolate, against DPPH-, ABTS-, and alkyl-radical, were observed during 32 hr of fermentation, but the changes were not statistically relevant. Composition ratios (% area by GC analysis) of lactic acid, xanthosine, and theobromine increased with fermentation time while hydroxymethylfurfural (HMF) and caffeine decreased after 32 hr of fermentation, in the order of xanthine (22.7%), theobrome (20.0%), lactic acid (14.9%), HMF (9.1%) and caffeine (9.0%). However, there was no remarkable changes in theobromine and caffeine contents in chocolate during fermentation.