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BackgroundOkra contains a viscous substance rich in water-soluble material, including fibers, pectin, proteoglycans, gum, and polysaccharides. This study explored the use of okra polysaccharides by microorganisms and their potential to improve microbiota.MethodsThe regulation of microcapsules prepared from okra polysaccharides with or without L. plantarum encapsulation on intestinal microbiota was assessed through 16S metagenomic analysis and short-chain fatty acids (SCFAs) in AppNL-G-F/NL-G-F mice (Alzheimer’s disease; AD model).ResultsWe found that Lactobacillaceae and Lactobacillus were majorly regulated by microcapsules prepared from okra polysaccharides in AD mice. Similarly, microcapsules prepared from okra polysaccharides with L. plantarum encapsulation markedly elevated the abundance of Lactobacillaceae and Lactobacillus and increased SCFAs in AD mice.ConclusionOur results suggest that microcapsules prepared from okra polysaccharides with or without L. plantarum encapsulation may improve intestinal microbiota by elevating Lactobacillus levels in AD mice.

Extracellular vesicles (EVs) are functional substances secreted by microbes and host cells, and it has been discovered that they participate in the interactions between different microorganisms. Our recent findings indicate that Limosilactobacillus reuteri-derived EVs have the potential to improve the intestinal microbiota of Oplegnathus fasciatus fish and inhibit pathogenic bacteria. Previous research has reported that the host intestinal cells play a regulatory role in the intestinal microbiota. This suggested that to investigate the mechanisms through which L. reuteri-derived EVs regulate the intestinal microbiota, a system that excludes interference from host intestinal cells should be established. In this study, an in vitro cultured intestinal bacteria system, without host factors, was used to simulate the intestinal microbiota of O. fasciatus fish. After adding L. reuteri-derived EVs to the system, the changes in the microbiota were analyzed. The results showed that L. reuteri-derived EVs effectively reduced the abundance of Vibrio spp. In the results of the in vitro experiments, it was also observed that L. reuteri-derived EVs have the ability to inhibit Vibrio alginolyticus. We further sequenced the small RNA contained in L. reuteri-derived EVs and found that these small RNAs can interfere with genes (LysR, pirin, MIpA/OmpV, CatB, and aspartate-semialdehyde dehydrogenase) related to the growth of V. alginolyticus. Taken together, the results indicate that in the absence of host involvement, the small RNAs present in L. reuteri-derived EVs have the function of inhibiting pathogenic bacteria and exhibit the potential to regulate the intestinal microbiota.

Rice straw is not easy to decompose, it takes a long time to compost, and the anaerobic bacteria involved in the decomposition process produce a large amount of carbon dioxide (CO2), indicating that applications for rice straw need to be developed. Recycling rice straw in agricultural crops is an opportunity to increase the sustainability of grain production. Several studies have shown that the probiotic population gradually decreases in the soil, leading to an increased risk of plant diseases and decreased biomass yield. Because the microorganisms in the soil are related to the growth of plants, when the soil microbial community is imbalanced it seriously affects plant growth. We investigated the feasibility of using composted rice stalks to artificially cultivate microorganisms obtained from the Oryza sativa-planted environment for analyzing the mycobiota and evaluating applications for sustainable agriculture. Microbes obtained from the water-submerged part (group-A) and soil part (group-B) of O. sativa were cultured in an artificial medium, and the microbial diversity was analyzed with internal transcribed spacer sequencing. Paddy field soil was mixed with fermented paddy straw compost, and the microbes obtained from the soil used for O. sativa planting were designated as group-C. The paddy fields transplanted with artificially cultured microbes from group-A were designated as group-D and those from group-B were designated as group-E. We found that fungi and yeasts can be cultured in groups-A and -B. These microbes altered the soil mycobiota in the paddy fields after transplantation in groups-D and -E compared to groups-A and -B. Development in O. sativa post treatment with microbial transplantation was observed in the groups-D and -E compared to group-C. These results showed that artificially cultured microorganisms could be efficiently transplanted into the soil and improve the mycobiota. Phytohormones were involved in improving O. sativa growth and rice yield via the submerged part-derived microbial medium (group-D) or the soil part-derived microbial medium (group-E) treatments. Collectively, these fungi and yeasts may be applied in microbial transplantation via rice straw fermentation to repair soil mycobiota imbalances, facilitating plant growth and sustainable agriculture. These fungi and yeasts may be applied in microbial transplantation to repair soil mycobiota imbalances and sustainable agriculture.

In recent years, probiotics have received considerable attention for improving the health of aquaculture organisms, such as fish and shrimp, by stimulating immune activity and increasing growth rates. Oplegnathus fasciatus is a common and economically important cultured fish species in Asia. In this study, we aimed to investigate the potential of lactic acid bacteria (LAB; Limosilactobacillus reuteri)-fermented feed to promote growth and enhance immune function in O. fasciatus. The feed contained the highest proportion of LAB after L. reuteri fermentation for 3 days in anaerobic conditions. Oplegnathus fasciatus was fed LAB-fermented feed for 30 days. The administration of LAB-fermented feed (live bacteria > 109 CFU/g) significantly increased the growth rate (weight gain = 174.8%; FCR = 4.23) and intestinal probiotic levels of O. fasciatus. After LAB-fermented feeding, the immunity index was evaluated by superoxide anion production, the phagocytic activity of leukocytes, and bactericidal and lysozyme activities in the serum of O. fasciatus. We found that LAB-fermented feed treatment potentially elevated the proportions of intestinal Bifidobacterium, Blautia, and Dorea species and reduced pathogenic bacterial growth (Acinetobacter, Escherichia_Shigella, and Megasphaera) in O. fasciatus. This study demonstrated that LAB-fermented feed containing extracellular vesicles improves growth performance and the inhibition of pathogenic Acinetobacter baumannii.

Resveratrol (RSV), obtained from dietary sources, has been shown to reduce trimethylamine oxide (TMAO) levels in humans, and much research indicates that TMAO is recognized as a risk factor for cardiovascular disease. Therefore, this study investigated the effects of RSV and RSV-butyrate esters (RBE) on the proliferation of co-cultured bacteria and HepG2 cell lines, respectively, and also investigated the changes in trimethylamine (TMA) and TMOA content in the medium and flavin-containing monooxygenase-3 (FMO3) gene expression. This study revealed that 50 µg/mL of RBE could increase the population percentage of Bifidobacterium longum at a rate of 53%, while the rate was 48% for Clostridium asparagiforme. In contrast, co-cultivation of the two bacterial strains effectively reduced TMA levels from 561 ppm to 449 ppm. In addition, regarding TMA-induced HepG2 cell lines, treatment with 50 μM each of RBE, 3,4′-di-O-butanoylresveratrol (ED2), and 3-O-butanoylresveratrol (ED4) significantly reduced FMO3 gene expression from 2.13 to 0.40–1.40, which would also contribute to the reduction of TMAO content. This study demonstrated the potential of RBE, ED2, and ED4 for regulating TMA metabolism in microbial co-cultures and cell line cultures, which also suggests that the resveratrol derivative might be a daily dietary supplement that will be beneficial for health promotion in the future.

Lactic acid bacteria and Bacillus species are not only microorganisms that are often used in fermented products and food industries but they are also considered human probiotics because their metabolites are beneficial to organisms [...]

Celluloid, the predecessor to plastic, was synthesized in 1869, and due to technological advancements, plastic products appear to be ubiquitous in daily life. The massive production, rampant usage, and inadequate disposal of plastic products have led to severe environmental pollution. Consequently, reducing the employment of plastic has emerged as a pressing concern for governments globally. This review explores microplastics, including their origins, absorption, and harmful effects on the environment and humans. Several methods exist for breaking down plastics, including thermal, mechanical, light, catalytic, and biological processes. Despite these methods, microplastics (MPs, between 1 and 5 mm in size) continue to be produced during degradation. Acknowledging the significant threat that MPs pose to the environment and human health is imperative. This form of pollution is pervasive in the air and food and infiltrates our bodies through ingestion, inhalation, or skin contact. It is essential to assess the potential hazards that MPs can introduce. There is evidence suggesting that MPs may have negative impacts on different areas of human health. These include the respiratory, gastrointestinal, immune, nervous, and reproductive systems, the liver and organs, the skin, and even the placenta and placental barrier. It is encouraging to see that most of the countries have taken steps to regulate plastic particles. These measures aim to reduce plastic usage, which is essential today. At the same time, this review summarizes the degradation mechanism of plastics, their impact on human health, and plastic reduction policies worldwide. It provides valuable information for future research on MPs and regulatory development.

Coffee flavor considerably depends on the fermentation process, with contributing factors including fermentation temperature, oxygen concentration, and microbial diversity. Efficient controlling of the fermentation can improve the quality of coffee beverages. Therefore, several studies on coffee fermentation processes have been conducted in various regions. The objective of this study was to assess the microbial diversity of coffee beans undergoing anaerobic fermentation at various temperatures (4 °C or 37 °C) and fermentation durations (12 h or 36 h) using full-length 16S rRNA sequencing. This analysis aimed to evaluate the inhibitory effects of the fermented metabolites against ochratoxin-producing Aspergillus niger. From our results, Acetobacter was identified as the dominant microbial community at higher fermentation temperatures, whereas Leuconostoc and Gluconobacter were the dominant genera at lower temperatures. However, at lower temperatures, changes in microbial communities were relatively slow. This study expands our knowledge of the microbial diversity involved in the anaerobic fermentation of coffee beans in Taiwan. The findings of this study can be used in future research to cultivate microorganisms linked to the quality and improve the quality of coffee beverages through fermentation.

Methylglyoxal (MG) is a highly reactive dicarbonyl aldehyde and a major precursor of advanced glycation end products that result in oxidative stress. Graptopetalum paraguayense E. Walther (WGP) is a herbal medicine of Taiwan with the hepatoprotective property. The aim of this study was to investigate the protective effects of the water extract of WGP on MG-induced liver damage in a rat model. The results showed that WGP lowered the total cholesterol level and the low-density lipoprotein cholesterol level. WGP could help normalize the MG level. The amelioration of inflammatory factors such as transformation growth factor-β1 was observed in the WGP treatment group. In another animal model, a high-fructose diet (HFD) was used to induce intestinal dysfunction in C57BL/6 mice. The results indicated that the HFD induction resulted in intestinal dysbiosis, including inflammation, microflora imbalances, and reductions in tight-junction proteins. However, both WGP and its active compound gallic acid could improve intestine function. According to the above, WGP can improve hyperlipidemia in the liver, inhibit inflammatory cytokine production, and regulate intestinal flora in mice, as well as enhance the intestinal barrier. These findings provide a basis for the development of health products.

In recent years, lactic acid bacteria, widely used in food fermentation, have been recognized as beneficial components of the human microbiome in which they play an important role [...]

Abstract Extracellular vesicle (EV)-mediated intercellular communication acts as a critical culprit in cancer development. The selective packaging of oncogenic molecules renders tumor-derived EVs capable of altering the tumor microenvironment and thereby modulating cancer developments that may contribute to drug resistance and cancer recurrence. Moreover, the molecular and functional characteristics of cancer through its development and posttreatment evolve over time. Tumor-derived EVs are profoundly involved in this process and can, therefore, provide valuable real-time information to reflect dynamic changes occurring within the body. Because they bear unique molecular profiles or signatures, tumor-derived EVs have been highlighted as valuable diagnostic and predictive biomarkers as well as novel therapeutic targets. In addition, the use of an advanced EV-based drug delivery system for cancer therapeutics has recently been emphasized in both basic and clinical studies. In this review, we highlight comprehensive aspects of tumor-derived EVs in oncogenic processes and their potential clinical applications.

Flower thinning is often used during the planting of fruit trees to improve fruit quality and promote large fruit. Flower buds become an agricultural by-product of the planting process. Pitaya (Hylocereus undatus) is a popular fruit in many tropical regions, which is widely cultivated in Southeast Asian countries. Probiotics such as Lactobacillus plantarum have been shown to exhibit an anti-obesity effect by regulating gut microbiota. This study investigated the effect of polysaccharides from pitaya flower buds (PFW) extracted with water on the regulation of gut microbiota and body weight control in mice fed with a high-fat diet. The effects of PFW on the growth of L. plantarum were analyzed and the propagation of L. plantarum was promoted in an aqueous solution containing PFW. In an in vivo study, mice were fed with a high-fat diet supplemented with PFW for 12 weeks; PFW treatment effectively controlled body weight and reduced short bowel syndrome of mice induced by the high-fat diet. Gut microbiota sequencing revealed that Lachnospiraceae and Lactobacillaceae were the main bacteria targeted by PFW. Moreover, transcript analysis demonstrated that PFW alleviated obesity through amino acid metabolism, carbohydrate metabolism, and glycan metabolism. Overall, PFW is a valuable food supplement that can regulate gut microbiota and may have potential to ameliorate the physiological damage caused by a high-fat diet.

(1) Background: The microbial phase in the vaginal environment has been found to regulate the physiological activity of host cells. Studies have demonstrated that abnormal microbial growth in the vagina and a significant reduction in the proportion of lactic acid bacteria promote the occurrence of spontaneous preterm birth (sPTB). However, the contributing mechanism remains unknown. (2) Methods: This study uses extracellular vesicles (EVs) secreted by the probiotic Lactobacillus crispatus, commonly found in the vagina, to explore their potential to attenuate placental cells caused by oxidative stress induction. (3) Results: We found that L. crispatus-derived EVs improved Akt phosphorylation and attenuated both cell senescence and death in placental cells caused by oxidative stress induction. In addition, L. crispatus-derived EVs enhanced the resistance to H2O2 induction mediated by increasing mitochondrial fusion. (4) Conclusion: This is the first study to demonstrate that L. crispatus in the vagina can not only regulate the physiological functions of placental cells through the delivery of L. crispatus-EVs but also reduce cell senescence. As cell senescence is related to the occurrence of sPTB, these results indicate that maintaining the population of L. crispatus in the vaginal environment should be an adjuvant treatment strategy to avoid sPTB.

Background: Soy sauce is applied as a seasoning in daily life in East Asia. High amounts of salt in soy sauce can inhibit microbial growth in its production and preservation. However, the elevated salt content in food might increase the health risk. Low salt fermentation is rarely used in soil sauce production because of the potential harmful lactic acid bacteria growth. Therefore, dilution after high salt fermentation is commonly used to reduce the salt concentration. Methods: This study aims to treat the low salt fermented soy sauce with a high hydrostatic pressure process (HPP) to eliminate the harmful bacteria and to analyze the microbial community change compared with that in traditional high salt fermentation. Results: The results showed that the bacterial diversity was increased in low-salt and high-pressure (LS-HP)-treated soy sauce, though the bacterial abundance was decreased. Relative abundance in high-salt (HS), low-salt (LS), and LS-HP-treated soy sauce showed specific bacterial strains in the LS-HP group. Similarly, the fungal diversity was also increased in LS-HP-fermented soy sauce and the detected OTUs were increased. The fungi sensitive to salinity and pressure were indicated in our results. Conclusions: The present study suggests the enhanced bacterial and fungal diversity and different microbial community in HS, LS, and LS-HP-treated soy sauce, as well as the availability of LS and HPP treatment on soy sauce production.

The present study is designed to investigate the anti-oral cancer properties of Solanum nigrum on oral squamous cell carcinoma. S. nigrum is a Chinese herb used for suppression of various cancers. However, the inhibition of S. nigrum on oral cancer is unclear. Therefore, human oral squamous cancer cells (SCC)-4 were used to evaluate the effect of aqueous extracts of S. nigrum (AESN) on cancer cell proliferation, cell cycle, mitochondrial function and apoptosis. The SCC-4 cells were treated by AESN to evaluate the inhibition of cell proliferation and mitochondrial function in vitro. Our results suggested that AESN markedly increased reactive oxygen species production. AESN also promoted caspase-9 and caspase-3 activation and subsequent triggering of the mitochondrial apoptotic pathway. The inhibition of glucose uptake was alleviated mediated by a dose-dependent manner in SCC-4 cells with AESN treatment for 24 h, resulting in mitochondrial fission. These results suggested that AESN has potential to be used as a functional food in adjuvant chemotherapy for treating human oral cancer by suppression of mitochondrial function.

White shrimp Litopenaeus vannamei is an important species of farmed shrimp. Intestinal bacterial composition and immune activity play important roles in regulating the health condition of shrimp. Lactic acid bacteria Limosilactobacillus fermentum SWP-AFFS02 was isolated from the intestine of sea fish Rachycentron canadum, and the potential of its effect on growth, immunity, and intestinal microbiota of L. vannamei shrimp was investigated. Shrimps received feed with or without the addition of 8 log CFU/g L. fermentum SWP-AFFS02 thrice a day for 8 weeks. After 8-week treatment, weight gain, feed conversion rate, and survival rate of shrimp were greater in the L. fermentum SWP-AFFS02-feed group than in the control group. L. fermentum SWP-AFFS02 treatment increased the number of granular cells and semi-granular cells and decreased hyaline cell number when compared to the control group. L. fermentum SWP-AFFS02 promoted prophenoloxidase (PO) activity through increasing immune-associated gene expression in the hepatopancreas of shrimp. In addition, administration of feed containing L. fermentum SWP-AFFS02 regulated intestinal microbiota via decreasing the ratio of pathogenic bacteria, such as Vibrionaceae and Enterobacteriaceae, in the intestine of shrimp. This study demonstrated that administration of L. fermentum SWP-AFFS02 effectively prevented infection of L. vannamei shrimp by regulating intestinal microbiota and enhancing immunity in shrimp to increase the growth and improve their health status, which acted as a probiotic and provided beneficial effects on shrimp.

Silver nanoparticles (AgNPs) have stable reactivity and excellent optical absorption properties. They can be applied in various industries, such as environmental protection, biochemical engineering, and analyte monitoring. However, synthesizing AgNPs and determining their appropriate dosage as a coloring substance are difficult tasks. In this study, to optimize the process of AgNP synthesis and obtain a simple detection method for trace mercury in the environment, we evaluate several factors—including the reagent addition sequence, reaction temperature, reaction time, the pH of the solution, and reagent concentration—considering the color intensity and purity of AgNPs as the reaction optimization criteria. The optimal process for AgNP synthesis is as follows: Mix 10 mM of silver nitrate with trisodium citrate in a hot water bath for 10 min; then, add 10 mM of sodium borohydride to produce the AgNPs and keep stirring for 2 h; finally, adjust the pH to 12 to obtain the most stable products. For AgNP-based mercury detection, the calibration curve of mercury over the concentration range of 0.1–2 ppb exhibits good linearity (R2 > 0.99). This study provides a stable and excellent AgNP synthesis technique that can improve various applications involving AgNP-mediated reactions and has the potential to be developed as an alternative to using expensive detection equipment and to be applied for the detection of mercury in food.

Polysaccharides isolated from fungus Cordyceps militaris display multi-biofunctions, such as immunostimulation, down-regulation of hyperlipidemia, and anti-cancer function. The occurrence of obesity and metabolic syndrome is related to the imbalance of gut microbiota. In this study, the effects of C. militaris and its fractions on modifying metabolic syndrome in mice were evaluated. Mice were fed a high-fat/high-sucrose diet (HFSD) for 14 weeks to induce body weight increase and hyperlipidemia symptoms in mice, and then the mice were simultaneously given a HFSD and C. militaris samples for a further 8 weeks. The results indicated that the fruit body, polysaccharides, and cordycepin obtained from C. militaris had different efficacies on regulating metabolic syndrome and gut microbiota in HFSD-treated mice. Polysaccharides derived from C. militaris decreased the levels of blood sugar and serum lipids in mice fed HFSD. In addition, C. militaris-polysaccharide treatment obviously improved intestinal dysbiosis through promoting the population of next generation probiotic Akkermansia muciniphila in the gut of mice fed HFSD. In conclusion, polysaccharides derived from C. militaris have the potential to act as dietary supplements and health food products for modifying the gut microbiota to improve the metabolic syndrome.

Clostridioides difficile infection (CDI) is a large intestine disease caused by toxins produced by the spore-forming bacterium C. difficile, which belongs to Gram-positive bacillus. Using antibiotics treatment disturbances in the gut microbiota and toxins produced by C. difficile disrupt the intestinal barrier. Some evidence indicates fecal microbiota transplantation and probiotics may decrease the risk of CDI recurrence. This study aimed to evaluate the efficacy of fermented mango by using the lactic acid bacteria Lactobacillus acidophilus and develop innovative products in the form of fermented mango jam. L. acidophilus-fermented mango products inhibited the growth of C. difficile while promoting the growth of next-generation probiotic Faecalibacterium prausnitzii. Both supernatant and precipitate of mango-fermented products prevented cell death in gut enterocyte-like Caco-2 cells against C. difficile infection. Mango-fermented products also protected gut barrier function by elevating the expression of tight junction proteins. Moreover, L. acidophilus-fermented mango jam with high hydrostatic pressure treatment had favorable textural characteristics and sensory quality.

Mango peels are usually discarded as waste; however, they contain phytochemicals and could provide functional properties to food and promote human health. This study aimed to determine the optimal lactic acid bacteria for fermentation of mango peel and evaluate the effect of mango peel on neuronal protection in Neuron-2A cells against amyloid beta (Aβ) treatment (50 μM). Mango peel can be fermented by different lactic acid bacteria species. Lactobacillus acidophilus (BCRC14079)-fermented mango peel produced the highest concentration of lactic acid bacteria (exceeding 108 CFU/mL). Mango peel and fermented mango peel extracts upregulated brain-derived neurotrophic factor (BDNF) expression for 1.74-fold in Neuron-2A cells. Furthermore, mango peel fermented products attenuated oxidative stress in Aβ-treated neural cells by 27%. Extracts of L. acidophilus (BCRC14079)-fermented mango peel treatment decreased Aβ accumulation and attenuated the increase of subG1 caused by Aβ induction in Neuron-2A cells. In conclusion, L. acidophilus (BCRC14079)-fermented mango peel acts as a novel neuronal protective product by inhibiting oxidative stress and increasing BDNF expression in neural cells.

Colorectal cancer is one of the most common cancers worldwide and chemotherapy is the main approach for the treatment of advanced and recurrent cases. Developing an effective complementary therapy could help to improve tumor suppression efficiency and control adverse effects from chemotherapy. Paris polyphylla is a folk medicine for treating various forms of cancer, but its effect on colorectal cancer is largely unexplored. The aim of the present study is to investigate the tumor suppression efficacy and the mechanism of action of the ethanolic extract from P. polyphylla (EEPP) in DLD-1 human colorectal carcinoma cells and to evaluate its combined effect with chemotherapeutic drug doxorubicin. The data indicated that EEPP induced DLD-1 cell death via the upregulation of the autophagy markers, without triggering p53- and caspase-3-dependent apoptosis. Moreover, EEPP treatment in combination with doxorubicin enhanced cytotoxicity in these tumor cells. Pennogenin 3-O-beta-chacotrioside and polyphyllin VI were isolated from EEPP and identified as the main candidate active components. Our results suggest that EEPP deserves further evaluation for development as complementary chemotherapy for colorectal cancer.

PT-peptide is derived from the anti-lipopolysaccharide factor of the swimming crab Portunus trituberculatus. The peptide, consisting of 34 amino acids, contains a lipopolysaccharide binding domain. In this study, we investigated the effect of PT-peptide encapsulated in raw milk-derived extracellular vesicles (EVs), designated as EVs-PT peptide, on immune regulation. The results showed that raw milk-derived EVs efficaciously delivered the PT-peptide into monocytes and elevated immune activity, including reactive oxygen species level, superoxide anion production, and phagocytosis. PT-peptide and EVs-PT peptide also elevated the secretion of cytokines, such as interferon-γ, interleukin-6, and tumor necrosis factor-α in human monocytic THP-1 cells. These results suggest that the PT-peptide could be developed as an immune stimulator.

The effects of dimerumic acid (DMA) on apoptosis prevention and insulin production in the glucose metabolite methylglyoxal (MG)-treated pancreatic RINm5F cells were evaluated. MG was found to induce apoptotic signal molecules mediated by oxidative stress in RINm5F cells, including caspase-3 and caspas-9, resulting in cell death and decreasing insulin production. In addition, DMA elevated insulin synthesis via up-regulating mammalian homologue of avian MafA/L-Maf (Maf-A) and pancreatic-duodenal homeobox-1 (PDX-1) and inhibited MG-mediated CCAAT/enhancer binding proteins-β (C/EBPβ) expression, which is a negative regulator for insulin production. Nuclear factor-erythroid2-related factor 2 (Nrf2) is essential for antioxidant responsive element (ARE)-mediated induction. Results indicated that nuclear translocation of Nrf2 was promoted by DMA in MG-treated RINm5F cells to increase heme oxygenase-1 (HO-1) and glutamate-cysteine ligase (GCL) expressions. We confirmed that DMA protected PDX-1, Maf-A, and insulin production against MG-induced oxidative stress mediating by Nrf2 in Nrf2-knockdown RINm5F cells. These results suggest that DMA exerts antioxidative ability to attenuate MG-induced pancreatic cell damage and elevates insulin level to improve diabetes.

The anti-obesity activity of Lactobacillus paracasei subsp. paracasei NTU 101 and Lactobacillus plantarum NTU 102 and their soy milk fermented products (SM101 and SM102) were investigated. Results indicated that the inhibition of 3T3-L1 differentiation and the accumulation of free fatty acids markedly increased in rats treated with SM101 and SM102. Moreover, the up-regulation and down-regulation of lipolysis and heparin-releasable lipoprotein lipase, respectively, were observed in the 3T3-L1 adipocytes of the SM101 and SM101 groups, and these effects of SM101 and SM102 were greater than unfermented soy milk (USM). We also found that SM101 and SM102 both improved obesity in Wistar rats fed with a high-fat diet (HFD) and that this improvement was stronger than that observed for USM. The level of serum leptin in HFD-induced rats was significantly elevated by the 5-week administration of SM101 and SM102 (106–1010 CFU/mL per rat per day); however, this activity was not promoted by USM. The anti-obesity activity of SM101 and SM102 may result from the increased daidzein and genistein levels that were observed during the fermentation by L. paracasei subsp. paracasei NTU 101 and L. plantarum NTU 102.

The effects of ankaflavin (AK) on adipokines level and insulin sensitivity were investigated. Mice were fed with high-fat diet (HFD) and AK to evaluate hyperglycemia and hyperlipidemia. Additionally, mature differentiated 3T3-L1 adipocytes were treated with AK or monascin (MS) to determine insulin signaling. Results showed that AK down-regulated serum and hepatic triacylglyceride (TG) and total cholesterol (TC) levels in mice, ameliorating hyperglycemia and hyperinsulinemia symptoms elicited by the HFD. AK elevated serum adiponectin levels in HFD-induced mice and mature 3T3-L1 adipocytes. The effect of AK on insulin sensitivity and adipokines secretion were abolished by peroxisome proliferator activated receptor-γ PPAR-γ antagonist GW9662. Moreover, we made the novel discovery that AK markedly promoted insulin receptor and Akt phosphorylation, and increased glucose uptake in mature 3T3-L1 adipocytes to a greater extent than did MS. Taken together, AK attenuated insulin resistance in HFD-induced mice and promoted insulin sensitivity in 3T3-L1 adipocytes through PPAR-γ activation.

Monascus has traditionally been used for the preparation of fermented products and as a food additive in Asia and is also a traditional Chinese medicine. The present review summarizes the underlying biochemical and molecular mechanisms that can explain anti-inflammation, antioxidation, hepatoprotection, inhibition of cancer cell invasion, and detoxification of dimerumic acid (DMA) isolated from Monascus-fermented products. DMA is an antioxidant that effectively inhibits liver damage and inflammation by attenuating oxidative stress in vitro and in vivo, which is stronger than silymarin, resveratrol, or curcumin. In addition, several lines of evidence have indicated that reactive oxygen species (ROS) promotes cancer cell invasion and suppress tumor development. DMA has been reported to attenuate ROS-induced invasion of SW620 (colorectal adenocarcinoma cells) greater than silymarin, resveratrol, and curcumin. These findings suggest that DMA has potential for development as a novel antioxidant for functional foods to act against several diseases-associated oxidative stress.

Ankaflavin (AK) is a yellow pigment isolated from Monascus-fermented product. The potential mechanism of AK-regulated dyslipidemia in high-fat diet hamsters was investigated. The results showed that AK treatment reduced plasma total cholesterol (TC) level in hamsters, elevated faecal TC and bile acid concentration, and protected high density apolipoprotein-cholesterol (HDL-C) from diminishing. We further used hepatocytes to demonstrate that AK stabilized HDL levels via nuclear factor-erythroid 2 related factor 2 (Nrf2) activation and downstream molecule haem oxygenase-1 (HO-1) expression, as well as increasing liver x receptor-α (LXRα) mRNA level to promote ATP-binding cassette transporter (ABCA1) and apolipoprotein-A1 (apo-A1) expression. AK increased low density apolipoprotein-cholesterol (LDL-C) expression to promote cholesterol absorption in hepatocytes, and resulted in cholesterol metabolism by cytochrome P450 7A1 (CYP7A1), leading to the conversion of cholesterol into bile acid. Taken together, AK may serve as a cholesterol lowering agent to improve dyslipidemia.

The protective effect of red mold rice (RMR) against liver injury in rats fed with a Zn-deficient diet for 12 weeks was investigated in this study. Rats were orally administered RMR (151 mg/kg body weight or 755 mg/kg body weight; 1×dose or 5×dose, respectively) with or without Zn once a day for 4 consecutive weeks. The severity of liver damage was evaluated by measuring the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in Zn-deficient rats. RMR significantly inhibited the elevation of serum ALT levels by Zn-deficient induction. Hepatic antioxidase activity was also significantly increased in the RMR+Zn group (RZ), thereby suppressing the productions of reactive oxygen species (ROS) and proinflammatory cytokines in the liver of Zn-deficient rats. These findings suggested that RMR exerted hepatoprotective effects against Zn deficiency-induced liver inflammation.

Chemotherapy, a major approach was used in carcinoma treatment, always involves the development of drug resistance as well as side-effects that affect the quality of patients’ lives. An association between epithelial-mesenchymal transition (EMT) and chemotherapy resistance was established recently. We demonstrate in this paper that the aqueous extract of Paris polyphylla (AEPP)—a traditional Chinese medicine—can be used in various cancer types for suppression of carcinogenesis. We evaluated the suppressions of EMT and mitochondrial activity by AEPP treatment in a high-glucose (HG) induced-human ovarian carcinoma cell line (OVCAR-3 cells). The mitochondrial morphology was investigated using MitoTracker Deep Red FM staining. Our results indicated that AEPP reduced the viability of OVCAR-3 cells considerably through induction of apoptosis. However, this inhibitory potential of AEPP was attenuated by HG induction in OVCAR-3 cells. The levels of estrogen-related receptor (ERR)-alpha activator and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha were elevated by HG induction, but were suppressed by AEPP treatment. Down-regulations of cell survival and EMT were oberved in OVCAR-3 cells through suppression of PGC-1alpha by AEPP treatment. These results were confirmed through PGC-1alpha knockdown and overexpression in OVCAR-3 cells. Thus, AEPP can be beneficial for treating ovarian cancer and has potential for development of an integrative cancer therapy against ovarian cancer proliferation, metastasis, and migration.

Chemotherapy is the main approach for treating advanced and recurrent carcinoma, but the clinical performance of chemotherapy is limited by relatively low response rates, drug resistance, and adverse effects that severely affect the quality of life of patients. An association between epithelial-mesenchymal transition (EMT) and chemotherapy resistance has been investigated in recent studies. Our recent studies have found that the aqueous extract of Solanum nigrum (AESN) is a crucial ingredient in some traditional Chinese medicine formulas for treating various types of cancer patients and exhibits antitumor effects. We evaluated the suppression of EMT in MCF-7 breast cancer cells treated with AESN. The mitochondrial morphology was investigated using Mitotracker Deep-Red FM stain. Our results indicated that AESN markedly inhibited cell viability of MCF-7 breast cancer cells through apoptosis induction and cell cycle arrest mediated by activation of caspase-3 and production of reactive oxygen species. Furthermore, mitochondrial fission was observed in MCF-7 breast cancer cells treated with AESN. In addition to elevation of E-cadherin, downregulations of ZEB1, N-cadherin, and vimentin were found in AESN-treated MCF-7 breast cancer cells. These results suggested that AESN could inhibit EMT of MCF-7 breast cancer cells mediated by attenuation of mitochondrial function. AESN could be potentially beneficial in treating breast cancer cells, and may be of interest for future studies in developing integrative cancer therapy against proliferation, metastasis, and migration of breast cancer cells.

Background: Advanced glycation end products (AGEs) signal through the receptor for AGE (RAGE), which can lead to hepatic fibrosis in hyperglycemia and hyperlipidemia. We investigated the inhibitory effect of aqueous extracts from Solanum nigrum (AESN) on AGEs-induced RAGE signaling and activation of hepatic stellate cells (HSCs) and hyperglycemia induced by high-fat diet with ethanol. Methods: An animal model was used to evaluate the anti-hepatic fibrosis activity of AESN in rats fed a high-fat diet (HFD; 30%) with ethanol (10%). Male Wistar rats (4 weeks of age) were randomly divided into four groups (n = 6): (1) control (basal diet); (2) HFD (30%) + ethanol (10%) (HFD/ethanol); (3) HFD/ethanol + AESN (100 mg/kg, oral administration); and (4) HFD/ethanol + pioglitazone (10 mg/kg, oral administration) and treated with HFD for 6 months in the presence or absence of 10% ethanol in dietary water. Results: We found that AESN improved insulin resistance and hyperinsulinemia, and downregulated lipogenesis via regulation of the peroxisome proliferator-activated receptor α (PPARα), PPARγ co-activator (PGC-1α), carbohydrate response element-binding protein (ChREBP), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) mRNA levels in the liver of HFD/ethanol-treated rats. In turn, AESN may delay and inhibit the progression of hepatic fibrosis, including α-smooth muscle actin (α-SMA) inhibition and MMP-2 production. Conclusions: These results suggest that AESN may be further explored as a novel anti-fibrotic strategy for the prevention of liver disease.

Miracle fruit (Synsepalum dulcificum) belongs to the Sapotaceae family. It can change flavors on taste buds, transforming acidic tastes to sweet. We evaluated various miracle fruit extracts, including water, butanol, ethyl acetate (EA), and hexane fractions, to determine its antioxidant effects. These extracts isolated from miracle fruit exerted potential for reduction of uric acid and inhibited xanthine oxidase activity in vitro and in monosodiumurate (MSU)-treated RAW264.7 macrophages. Moreover, we also found that the butanol extracts of miracle fruit attenuated oxonic acid potassium salt-induced hyperuricaemia in ICR mice by lowering serum uric acid levels and activating hepatic xanthine oxidase. These effects were equal to those of allopurinol, suggesting that the butanol extract of miracle fruit could be developed as a novel anti-hyperuricaemia agent or health food.

Pardaxin (H-GFFALIPKIISSPLFKTLLSAVGSALSSSGGQE-OH), a 33-amino-acid polypeptide, is an antimicrobial peptide (AMP) isolated from the marine fish species Pardachirus marmoratus. Pardaxin shows antibacterial and antitumor activities. However, pardaxin-induced inhibition of oral cancer and the mechanism of tumor reduction in buccal pouch carcinogenesis after pardaxin painting remain undetermined. Additionally, the toxic effects of pardaxin on normal tissue remain unclear. The present study investigated the anticancer activity of pardaxin in oral squamous cell carcinoma (OSCC) cells in the hamster buccal pouch model with or without 7,12-dimethylbenz[a]anthracene (DMBA) pretreatment. This is the first study to confirm the effects of pardaxin on normal tissue and its nontoxic effects in vivo. Cell viability assays and colony formation tests in OSCC cell lines (SCC-4) demonstrated that pardaxin reduced cell viability in a dose-dependent manner. Immunofluorescence staining of cleaved caspase-3 in SCC-4 cells revealed that expression of activated caspase-3 in SCC-4 cells significantly increased after 24-h treatment with pardaxin. Additionally, a cell cycle analysis indicated that pardaxin treatment resulted in the cell cycle arrest of SCC-4 cells in the G2/M phase, thereby limiting cell proliferation. Furthermore, pardaxin treatment substantially alleviated carcinogenesis in the DMBA-induced hamster buccal pouch model by lowering prostaglandin E2 levels. These results suggest that pardaxin is a potential marine drug for adjuvant chemotherapy for human OSCC and oral cancer.