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Abstract The mammalian target of rapamycin (mTOR) signaling pathway efficiently regulates the energy state of cells and maintains tissue homeostasis. Dysregulation of the mTOR pathway has been implicated in several human diseases. Rapamycin is a specific inhibitor of mTOR and pharmacological inhibition of mTOR with rapamycin promote cardiac cell generation from the differentiation of mouse and human embryonic stem cells. These studies strongly implicate a role of sustained mTOR activity in the differentiating functions of embryonic stem cells; however, they do not directly address the required effect for sustained mTOR activity in human cardiac progenitor cells. In the present study, we evaluated the effect of mTOR inhibition by rapamycin on the cellular function of human cardiac progenitor cells and discovered that treatment with rapamycin markedly attenuated replicative cell senescence in human cardiac progenitor cells (hCPCs) and promoted their cellular functions. Furthermore, rapamycin not only inhibited mTOR signaling but also influenced signaling pathways, including STAT3 and PIM1, in hCPCs. Therefore, these data reveal a crucial function for rapamycin in senescent hCPCs and provide clinical strategies based on chronic mTOR activity.

Abstract Background General antiviral agents such as oseltamivir are associated with certain adverse effects and the emergence of resistance. This study investigated the phytochemical properties, antiviral activities, and safety of three herbs used in traditional Korean medicine. Methods Extracts of three medicinal herbs (Brassica juncea, Forsythia suspensa, and Inula britannica) were prepared using ethanol or water. The total phenolic, flavonoid, and saponin content, condensed tannin content, and reducing sugar content of the herb extracts were determined via phytochemical screening. Tandem mass analysis was performed using an ultra-performance liquid chromatography (UPLC)-electrospray ionization (ESI)-Q/Orbitrap instrument. Virus titrations were determined via tissue culture infective dose (TCID50) and cytotoxicity assays. Hemolysis and hepatotoxicity were measured to determine safety. Results Among the three medicinal herbs, F. suspensa showed the highest concentration of phenolic compounds, flavonoids, and saponins. The number of phytochemical compounds detected via tandem mass analysis of B. juncea, F. suspensa, and I. britannica was 5 (including sinigrin, m/z [M-H] = 358.02), 14 (including forsythoside A, m/z [M-H] = 623.19), and 18 (including chlorogenic acid, m/z [M-H] = 353.20), respectively. The antiviral effects of the B. juncea extracts (ethanol and water) and I. britannica extract (ethanol) were further investigated. The ethanol extract of B. juncea showed a 3 Log TCID50/25 μL virus titration reduction and the water extract showed a selectivity index of 13.668 against infected influenza H1N1 virus A/NWS/33. The B. juncea extracts did not show hemolysis activities and hepatotoxicity (

Background: Ginsenosides, which are bioactive components in ginseng, can be converted to smaller compounds for improvement of their pharmacological activities. The conversion methods include heating; acid, alkali, and enzymatic treatment; and microbial conversion. The aim of this study was to determine the bioconversion of ginsenosides in fermented red ginseng extract (FRGE). Methods: Red ginseng extract (RGE) was fermented using Lactobacillus plantarum KCCM 11613P. This study investigated the ginsenosides and their antioxidant capacity in FRGE using diverse methods. Results: Properties of RGE were changed upon fermentation. Fermentation reduced the pH value, but increased the titratable acidity and viable cell counts of lactic acid bacteria. L. plantarum KCCM 11613P converted ginsenosides Rb2 and Rb3 to ginsenoside Rd in RGE. Fermentation also enhanced the antioxidant effects of RGE. FRGE reduced 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and reducing power; however, it improved the inhibition of β-carotene and linoleic acid oxidation and the lipid peroxidation. This suggested that the fermentation of RGE is effective for producing ginsenoside Rd as precursor of ginsenoside compound K and inhibition of lipid oxidation. Conclusion: This study showed that RGE fermented by L. plantarum KCCM 11613P may contribute to the development of functional food materials. Keywords: antioxidant effect, bioconversion, ginsenoside, Lactobacillus plantarum KCCM 11613P, red ginseng extract

The flower of Inula britannica contains various phenolic compounds with prophylactic properties. This study aimed to determine the anti-adipogenic effect of an I. britannica flower aqueous extract (IAE) and its underlying mechanisms in the 3T3-L1 preadipocytes and to identify the phenolic compounds in the extract. Treatment with IAE inhibited the adipogenesis of 3T3-L1 preadipocytes by showing a dose-dependently suppressed intracellular lipid accumulation and significantly mitigated expression levels of lipogenesis- and adipogenesis-associated biomarkers including transcription factors. IAE exerted an anti-adipogenic effect through the modulation of the early phases of adipogenesis including mitotic clonal expansion (MCE). Treatment with IAE inhibited MCE by arresting the cell cycle at the G0/G1 phase and suppressing the activation of MCE-related transcription factors. Furthermore, IAE inhibited adipogenesis by regulating the extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Protocatechuic acid, chlorogenic acid, kaempferol-3-O-glucoside, and 6-methoxyluteolin, which are reported to exhibit anti-adipogenic properties, were detected in IAE. Therefore, modulation of early phases of adipogenesis, especially MCE, is a key mechanism underlying the anti-adipogenic activity of IAE. In summary, the anti-obesity effects of IAE can be attributed to its phenolic compounds, and hence, IAE can be used for the development of anti-obesity products.

The purpose of this study was to evaluate the probiotic characteristics and neuroprotective effects of bacteria isolated from Korean fermented foods. Three bacterial strains (Lactobacillus fermentum KU200060, Lactobacillus delbrueckii KU200171, and Lactobacillus buchneri KU200793) showed potential probiotic properties, such as high tolerance against artificial gastric juice and bile salts, sensitivity to antibiotics, nonproduction of carcinogenic enzymes, and high adhesion to intestinal cells. Heat-killed L. fermentum KU200060 and L. buchneri KU200793 showed higher antioxidant activity than heat-killed L. delbrueckii KU200171. The conditioned medium (CM) was used to evaluate the reaction between HT-29 cells and each heat-killed strain. All CMs protected SH-SY5Y cells from 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity. The expression of brain-derived neurotropic factor (BDNF) mRNA in HT-29 cells treated with CM containing heat-killed L. buchneri KU200793 was the highest. The CM significantly reduced the Bax/Bcl-2 ratio and increased BDNF mRNA expression in SH-SY5Y cells treated with MPP+. These results indicate that L. buchneri KU200793 can be used as a prophylactic functional food, having probiotic potential and neuroprotective effects.

A mixed natural preservative, including grapefruit seed extract (GSE), cinnamaldehyde (CA), and nisin, was investigated for the reduction of Listeria monocytogenes growth on lettuce and raw pork loin. The MIC of each natural preservative was investigated for L. monocytogenes strains tested. Following central composite design, lettuce and pork loin were inoculated with a cocktail of three strains of L. monocytogenes (ATCC 15313, H7962, and NADC 2045 [Scott A]) and treated with the mixed natural preservative that included GSE (0.64 to 7.36 ppm), CA (1.6 to 18.4 ppm), and nisin (0.48 to 5.5 ppm). The MIC of GSE was 31.25 ppm in tested L. monocytogenes strains, and of CA was 500 and 1,000 ppm in L. monocytogenes ATCC 15313 and the other L. monocytogenes strains, respectively. The MIC of nisin was 250 ppm. The R2 value of this model was more than 0.9, and the lack of fit was not significant. The mixed natural preservative showed a synergistic antimicrobial effect and reduced the growth of L. monocytogenes by 4 to 5 log CFU/g on lettuce. In addition, the reduction of L. monocytogenes on pork loin was 3 log CFU/g. The mixed natural preservative, which consisted of GSE (6 to 8 ppm), CA (15 to 20 ppm), and nisin (5 to 6 ppm), increased the antibacterial effect against L. monocytogenes. These results suggest that the use of the mixed natural preservative could reduce the economic cost of food preparation, and response surface methodology is considered effective when measuring synergy among antimicrobials. [ABSTRACT FROM AUTHOR]

Abstract Background The Kellgren-Lawrence (KL) grading system is the most widely used method to classify the severity of osteoarthritis (OA) of the knee. However, due to ambiguity of terminology, the KL system showed inferior inter- and intra-observer reliability. For a more reliable evaluation, we recently developed novel deep learning (DL) software known as MediAI-OA to extract each radiographic feature of knee OA and to grade OA severity based on the KL system. Methods This research used data from the Osteoarthritis Initiative for training and validation of MediAI-OA. 44,193 radiographs and 810 radiographs were set as the training data and used as validation data, respectively. This AI model was developed to automatically quantify the degree of joint space narrowing (JSN) of medial and lateral tibiofemoral joint, to automatically detect osteophytes in four regions (medial distal femur, lateral distal femur, medial proximal tibia and lateral proximal tibia) of the knee joint, to classify the KL grade, and present the results of these three OA features together. The model was tested by using 400 test datasets, and the results were compared to the ground truth. The accuracy of the JSN quantification and osteophyte detection was evaluated. The KL grade classification performance was evaluated by precision, recall, F1 score, accuracy, and Cohen's kappa coefficient. In addition, we defined KL grade 2 or higher as clinically significant OA, and accuracy of OA diagnosis were obtained. Results The mean squared error of JSN rate quantification was 0.067 and average osteophyte detection accuracy of the MediAI-OA was 0.84. The accuracy of KL grading was 0.83, and the kappa coefficient between the AI model and ground truth was 0.768, which demonstrated substantial consistency. The OA diagnosis accuracy of this software was 0.92. Conclusions The novel DL software known as MediAI-OA demonstrated satisfactory performance comparable to that of experienced orthopedic surgeons and radiologists for analyzing features of knee OA, KL grading and OA diagnosis. Therefore, reliable KL grading can be performed and the burden of the radiologist can be reduced by using MediAI-OA.

The bioactive compounds and probiotic properties of three Saccharomyces cerevisiae strains isolated from cucumber jangajji were investigated. The β-glucan contents of S. cerevisiae KU200270, KU200280, and KU200284 were 4.09%, 7.45%, and 13.97%, respectively, and the glutathione contents of the strains were in the range of 3.19–6.03 mg/g dry cells. The l-ornithine and spermidine contents were 2.98–4.29 and 4.29–4.55 mg/g dry cells, respectively. All strains showed the ability to protect DNA from oxidative damage. The S. cerevisiae strains were highly resistant to both artificial gastric and bile juices. The epithelial cell adhesion of S. cerevisiae KU200284 was the highest at 16.38%, while that of the other strains was >5%. The S. cerevisiae strains produced esterase, leucine arylamidase, acid phosphatase, and α-glucosidase and showed no toxicity toward MRC-5 cells. These results suggest that the isolated S. cerevisiae strains have potential as probiotics and can be used starter cultures for functional foods.

ε-Polylysine (ε-PL) is a safe food additive that is used in the food industry globally. This study evaluated the antimicrobial and antibiofilm activity of antibacterial peptides (ε-PL) against food poisoning pathogens detected in chicken (Salmonella Enteritidis, Listeria monocytogenes, and Escherichia coli). The results showed that minimum inhibitory concentrations (MICs) ranged between 0.031–1.0 mg/mL, although most bacterial groups (75%) showed MICs of 1.0 mg/mL. The reduction in the cell viability of pathogens due to ε-PL depended on the time and concentration, and 1/2 × MIC of ε-PL killed 99.99% of pathogens after 10 h of incubation. To confirm biofilm inhibition and degradation effects, crystal violet assay and confocal laser scanning microscopy (CLSM) were used. The biofilm formation rates of four bacterial groups (Salmonella, Listeria, E. coli, and multi-species bacteria) were 10.36%, 9.10%, 17.44%, and 21.37% at 1/2 × MIC of ε-PL, respectively. Additionally, when observed under a CLSM, ε-PL was found to induce biofilm destruction and bacterial cytotoxicity. These results demonstrated that ε-PL has the potential to be used as an antibiotic and antibiofilm material for chicken meat processing.

This study was conducted to investigate the production of whey protein hydrolysates, examining the physiochemical properties with five enzyme types named alcalase, protease S, protease M, trypsin, and pepsin. Whey protein concentrate was adjusted by ultrafiltration, increasing the whey content to 135% that of initial levels. The hydrolysates have been shown to improve the characteristics of a number of food products, and the type of enzyme has a considerable influence on the end result of hydrolysates production. Bulk density, solubility, NPN, foaming capacity, and the degree of hydrolysis were increased with hydrolysis time. Maximum bulk density was shown by protease S. Pepsin and alcalase gradually increased the foaming capacity, resulting in a comparatively lower pH and a lower degree of hydrolysis. The highest degree of hydrolysis was shown by protease M. The highest NPN value was provided by pepsin, which was much greater than that of other enzymes. There was no significant difference in NPN according to the enzyme type applied. All hydrolysates in alkaline media were shown more than 50% solubility. HMF contents were also shown an obvious difference with the enzyme type. [ABSTRACT FROM AUTHOR]