Age-related dysregulation of intestinal epithelium fucosylation is linked to an increased risk of colon cancer.

Colon cancer affects people of all ages. However, its frequency, as well as the related morbidity and mortality, are high among older adults. The complex physiological changes in the aging gut substantially limit the development of cancer therapies. Here, we identify a potentially unique intestinal microenvironment that is linked with an increased risk of colon cancer in older adults. Our findings show that aging markedly influenced persistent fucosylation of the apical surfaces of intestinal epithelial cells, which resulted in a favorable environment for tumor growth. Furthermore, our findings shed light on the importance of the host-commensal interaction, which facilitates the dysregulation of fucosylation and promotes tumor growth as people get older. We analyzed colonic microbial populations at the species level to find changes associated with aging that could contribute to the development of colon cancer. Analysis of single-cell RNA-sequencing data from previous publications identified distinct epithelial cell subtypes involved in dysregulated fucosylation in older adults. Overall, our study provides compelling evidence that excessive fucosylation is associated with the development of colon cancer, that age-related changes increase vulnerability to colon cancer, and that a dysbiosis in microbial diversity and metabolic changes in the homeostasis of older mice dysregulate fucosylation levels with age.

Investigation of antioxidant, antibacterial, antidiabetic, and cytotoxicity potential of silver nanoparticles synthesized using the outer peel extract of Ananas comosus (L.).

Currently, green nanotechnology-based approaches using waste materials from food have been accepted as an environmentally friendly and cost-effective approach with various biomedical applications. In the current study, AgNPs were synthesized using the outer peel extract of the fruit Ananas comosus (AC), which is a food waste material. Characterization was done using UV-visible spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, scanning electronic microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) analyses. The formation of AgNPs has confirmed through UV-visible spectroscopy (at 485 nm) by the change of color owing to surface Plasmon resonance. Based on the XRD pattern, the crystalline property of AgNPs was established. The functional group existing in AC outer peel extract accountable for the reduction of Ag+ ion and the stabilization of AC-AgNPs was investigated through FT-IR. The morphological structures and elemental composition was determined by SEM and EDX analysis. With the growing application of AgNPs in biomedical perspectives, the biosynthesized AC-AgNPs were evaluated for their antioxidative, antidiabetic, and cytotoxic potential against HepG2 cells along with their antibacterial potential. The results showed that AC-AgNPs are extremely effective with high antidiabetic potential at a very low concentration as well as it exhibited higher cytotoxic activity against the HepG2 cancer cells in a dose-dependent manner. It also exhibited potential antioxidant activity and moderate antibacterial activity against the four tested foodborne pathogenic bacteria. Overall, the results highlight the effectiveness and potential applications of AC-AgNPs in biomedical fields such as in the treatment of acute illnesses as well as in drug formulation for treating various diseases such as cancer and diabetes. Further, it has applications in wound dressing or in treating bacterial related diseases.

Analysis of α-dicarbonyl compounds and volatiles formed in Maillard reaction model systems.

In this study, production of three α-dicarbonyl compounds (α-DCs) including glyoxal (GO), methylglyoxal (MGO), and diacetyl (DA) as well as volatile flavor compounds was analyzed using Maillard reaction (MR) model systems. A total of 16 model systems were assembled using four amino acids and four reducing sugars, and reactions were performed at 160 °C and pH 9. Determination of α-DCs was conducted using a gas chromatography/nitrogen phosphorous detector (GC-NPD) after derivatization and liquid-liquid extraction. α-DC levels in MR model systems were 5.92 to 39.10 µg/mL of GO, 3.66 to 151.88 µg/ml of MGO, and 1.10 to 6.12 µg/mL of DA. The highest concentration of total α-DCs was found in the fructose-threonine model system and the lowest concentration in the lactose-cysteine model system. Volatile flavor compounds were analyzed using solid-phase micro-extraction (SPME) followed by GC-mass spectrometry (GC-MS). Different volatile flavor compound profiles were identified in the different MR model systems. Higher concentrations of α-DCs and volatile flavor compounds were observed in monosaccharide-amino acid MR model systems compared with disaccharide-amino acid model systems.

Enterococcus faecalis EF-2001 protects DNBS-induced inflammatory bowel disease in mice model.

Recent studies have demonstrated the immunomodulatory effects of heat-killed lactic acid bacteria. The aim of this study was to evaluate the protective effect of heat-killed Enterococcus faecalis EF-2001 (EF-2001) on a model of inflammatory bowel disease (IBD). A total of 28 female NC/Nga mice were divided into 4 treatment groups. Controls were fed a normal commercial diet. In the experimental groups, colitis was induced by rectal administration of dinitrobenzene sulfonic acid. Two groups were orally administered 2 and 17 mg/kg EF-2001, respectively. EF-2001 treatment decreased the expression of several cytokines, including cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), interferon (IFN)-γ, interleukin (IL)-1ß, and IL-6 in inflamed colon compared to the DNBS alone group. In addition, EF-2001 suppressed DNBS-induced colonic tissue destruction. Therefore, this study strongly suggests that EF-2001 could alleviate the inflammation associated with mouse IBD.

Biosynthesis of silver nanoparticle using extract of Zea mays (corn flour) and investigation of its cytotoxicity effect and radical scavenging potential.

Silver nanoparticles (AgNPs) possesses a number of exceptional pharmaceutical properties and applications as compared with other types of metallic nanoparticles. Currently, AgNPs was biosynthesized using an aqueous extract of Zea mays L. (corn flour) powder. Further, the effect of concentration of reagents, extract, temperature and time of synthesis was also studied along with the cytotoxicity and radical scavenging potential. UV-vis spectra of AgNPs gave a surface plasmon resonance at ~420 nm. The absorption peak became sharp with the increase in time. AgNPs with monodispersed and aggregated spherical shape was observed by SEM image followed by its confirmation via strong signal in silver region of EDX spectrum. The XRD spectra confirmed its crystallinity and face-centered cubic structure. FT-IR spectra reveal the presence of phytocompounds in the synthesis of AgNPs. Further, the AgNPs exhibited strong cytotoxicity potential against HepG2 cells and its viability declined with an increase in the concentration of AgNP with respect to the control cells. It also demonstrated reasonable radical scavenging potential in terms of DPPH and ABTS scavenging, and reducing power tests. Taken together, these results of the current investigation stated that AgNPs could be beneficial in biomedical applications particularly for treatment of cancer disease along with its applications in pharmaceutical industries for the formulation of new drugs.

Effect of cinnamamides on atopic dermatitis through regulation of IL-4 in CD4+ cells.

This study aimed to evaluate the effects of cinnamamides on atopic dermatitis (AD) and the mechanisms underlying these effects. To this end, the actions of two cinnamamides, (E)-3-(4-hydroxyphenyl)-N-phenylethyl acrylamide (NCT) and N-trans-coumaroyltyramine (NCPA), were determined on AD by orally administering them to mice. Oral administration of the cinnamamides ameliorated the increase in epidermal and dermal thickness as well as mast cell infiltration. Cinnamamides suppressed serum immunoglobulin (Ig) levels and expression of T-helper (Th)1/Th2 cytokines. Moreover, cinnamamides suppressed interleukin (IL)-4, which plays a crucial role in preparing naïve clusters of differentiation (CD)4+ T cells, and decreased the cervical lymph node size and weight. Interestingly, in almost all cases, NCPA exhibited higher anti-AD activity compared to NCT. These results strongly indicate that NCPA may have potential as an anti-AD agent, and further mechanistic comparative studies of NCT and NCPA are required to determine the cause of differences in biological activity.

Validation of analytical method for furan determination in eight food matrices and its levels in various foods.

In this study, an automated solid-phase microextraction coupled with gas chromatography and mass spectrometry method was developed and validated for the determination of furan in eight matrices including ham, milk, apple juice, rice porridge, peanut butter, flatfish, tuna (canned) and seaweed. The calibration curves were highly linear (r2  > 0.990) and the limit of detection and limit of quantification ranged from 0.01-0.02 and 0.04-0.06 ng/g, respectively. The recovery ranged from 77.81-111.47%. The validated method was used to analyse the furan levels in 120 foods. The highest levels of furan were detected in black tea (172.05 ng/g) and red ginseng extract (89.27 ng/g). Whelk (canned) contained a high furan content (21.34 ng/g) among the seafood samples.

Investigation of the Anti-Prostate Cancer Properties of Marine-Derived Compounds.

This review focuses on marine compounds with anti-prostate cancer properties. Marine species are unique and have great potential for the discovery of anticancer drugs. Marine sources are taxonomically diverse and include bacteria, cyanobacteria, fungi, algae, and mangroves. Marine-derived compounds, including nucleotides, amides, quinones, polyethers, and peptides are biologically active compounds isolated from marine organisms such as sponges, ascidians, gorgonians, soft corals, and bryozoans, including those mentioned above. Several compound classes such as macrolides and alkaloids include drugs with anti-cancer mechanisms, such as antioxidants, anti-angiogenics, antiproliferatives, and apoptosis-inducing drugs. Despite the diversity of marine species, most marine-derived bioactive compounds have not yet been evaluated. Our objective is to explore marine compounds to identify new treatment strategies for prostate cancer. This review discusses chemically and pharmacologically diverse marine natural compounds and their sources in the context of prostate cancer drug treatment.

Changes in the amino acid profiles and free radical scavenging activities of Tenebrio molitor larvae following enzymatic hydrolysis.

Tenebrio molitor (T. molitor) larvae provide food at low environmental cost and contribute positively to livelihoods. In this research, we compared the amino acids compositions and antioxidant activities of various extracts of T. molitor to enhance their quality as food. For the comparison, distilled water extracts, enzymatic hydrolysates, and condensed enzymatic hydrolysates of T. molitor larvae were prepared. Their amino acids (AAs) profiles and antioxidant activities, including ferric-reducing antioxidant power, oxygen radical absorption capacity, and DPPH, hydroxyl radical, and hydrogen peroxide radical scavenging properties assay were analyzed. DW extracts had the lowest AAs contents and antioxidant activity compared with enzymatic extracts. Condensed hydrolysates with a combination of alcalase and flavourzyme (C-A+F) exhibited the highest levels of total free AAs (11.1759 g/100 g). C-A+F produced higher total hydrolyzed AAs (32.5292 g/100 g) compared with the other groups. The C-A+F possessed the strongest antioxidant activity. Notably, the antioxidant activities of the hydrolysates and the total hydrolyzed AAs amount were correlated. Taken together, our findings showed that C-A+F was a promising technique for obtaining extracts of T. molitor larvae with antioxidant activity as potential nutritious functional food.

The Effects of Aronia melanocarpa 'Viking' Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS/NFATc1 Signaling.

This study aimed to determine the anti-osteoclastogenic effects of extracts from Aronia melanocarpa 'Viking' (AM) and identify the underlying mechanisms in vitro. Reactive oxygen species (ROS) are signal mediators in osteoclast differentiation. AM extracts inhibited ROS production in RAW 264.7 cells in a dose-dependent manner and exhibited strong radical scavenging activity. The extracts also attenuated the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts. To attain molecular insights, the effect of the extracts on the signaling pathways induced by receptor activator of nuclear factor kappa B ligand (RANKL) were also investigated. RANKL triggers many transcription factors through the activation of mitogen-activated protein kinase (MAPK) and ROS, leading to the induction of osteoclast-specific genes. The extracts significantly suppressed RANKL-induced activation of MAPKs, such as extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and p38 and consequently led to the downregulation of c-Fos and nuclear factor of activated T cells 1 (NFATc1) protein expression which ultimately suppress the activation of the osteoclast-specific genes, cathepsin K, TRAP, calcitonin receptor and integrin ß3. In conclusion, our findings suggest that AM extracts inhibited RANKL-induced osteoclast differentiation by downregulating ROS generation and inactivating JNK/ERK/p38, nuclear factor kappa B (NF-κB)-mediated c-Fos and NFATc1 signaling pathway.

Role of phytochemicals in the modulation of miRNA expression in cancer.

MicroRNAs (miRNAs) are single-stranded non-coding endogenous RNAs linked with normal developmental and physiological processes. Recent studies have demonstrated that the dysregulation of miRNAs plays an important role in the beginning, progression, and metastasis of many cancers. Additionally, they are involved in the regulation of the epithelial-to-mesenchymal transition (EMT) in many cancer cells. Several studies have suggested that phytochemicals play an important role in the modulation of miRNA expression, which is related to changes in oncogenes, tumour suppressors, and cancer-related protein expression. Hence, phytonutrients can suppress tumour development, prevent metastasis, reverse the EMT, and improve drug sensitivity via the modulation of miRNA expression. In this review, we discuss tumour-suppressing and oncogenic miRNAs and the mechanism of action for miRNAs as well as the role of phytochemicals in the modulation of miRNAs in various cancer cells.

Topical application of Moringa oleifera leaf extract ameliorates experimentally induced atopic dermatitis by the regulation of Th1/Th2/Th17 balance.

BACKGROUND: Moringa oleifera (M. oleifera) is widely cultivated in tropical and subtropical regions and has been used as a vegetable and in traditional medicine. In this study, the anti-atopic dermatitis activity of the ethanol extract of M. oleifera leaf was investigated in vitro and in vivo. METHODS: For the in vitro study, HaCaT human keratinocytes were used for cytokines and MAPKinase assay. In the in vivo study, M. oleifera leaf ethanolic extract (MO) was topically applied to BALB/c mice with Dermatophagoides farinae extract (DFE; house dust mite extract)- and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD). RESULTS: The expression of TNF-α, CCL17, IL-1ß, IL-6 pro-inflammatory cytokine-related mRNA, and mitogen-activated protein kinases (MAPKs) in TNF-α/IFN-γ-induced HaCaT keratinocytes were reduced by MO. Epidermal and dermal ear thickness, mast cell infiltration, serum immunoglobulin levels, as well as gene expression of various cytokines in the ear tissue, lymph nodes, and splenocytes were improved by treatment with MO. In addition, MO reduced the expression of retinoic acid-related orphan receptor γT (RORγT), thymic stromal lymphopoietin (TSLP), and mannose receptor (CD206) mRNA in the ear tissue and improved cervical lymph node size. CONCLUSION: The results of this study strongly suggest the beneficial effects of MO on AD via the regulation of inflammatory responses.

Role of phytochemicals in the inhibition of epithelial-mesenchymal transition in cancer metastasis.

Epithelial-mesenchymal transition (EMT) is the process by which epithelial cells become mesenchymal cells, gaining fibroblast-like properties and displaying reduced intercellular adhesion and increased motility. EMT plays an important role in cancer metastasis. Suppressing or reversing EMT is therefore an important way of controlling various cancers. Phytochemicals are important sources of anticancer lead molecules. Natural products have been shown to safely suppress or reverse EMT via the inhibition of associated signalling pathways in various cancer cells. In the present review, we discuss the relevant factors and the role of EMT in cancer metastasis. We then present examples of phytochemicals with a role in the inhibition and reversal of EMT in various cancers, focusing on reports from 2012 to 2016.

In vitro antioxidant and anti-inflammatory activities of Korean blueberry (Vaccinium corymbosum L.) extracts

Objective: To investigate in vitro antioxidant and anti-inflammatory activities of Korean blueberry (Vaccinium corymbosum L.). Methods:Total phenolic and flavonoid contents of the Korean blueberry water and ethanol extracts were determined before determining the potential of the extracts as antioxidant. Antioxidant activity of the extracts was determined by following some well established methods for free radical scavenging such as 2,2-diphenyl-picrylhydrazyl hydrate, 1,2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonicacid), free radical induced DNA damage, superoxide dismutase-like and catalase assay etc. Furthermore, 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan and nitric oxide assay were performed to determine the anti-inflammatory activity of the extracts. Results:Total phenolic contents were found (115.0±3.0) and (4.2±3.0) mg GAE/100 g fresh mass for both extracts, respectively and flavonoid contents were (1942.8±7.0) and (1292.1±6.0) mg CE/100g fresh mass for water and ethonal extracts, respectively. Both the extracts displayed significant scavenging activity of some radicals such as 2,2-diphenyl-picrylhydrazyl hydrate (IC50 at 1.8 mg/mL and 2.05 mg/mL, respectively), 1,2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonicacid) (IC50 at 1.5 mg/mL and 1.6 mg/mL, respectively) and nitrite (IC50 at 1.7 mg/mL and 1.5 mg/mL, respectively)etc. The extracts were found to prevent inflammation as well by reducing nitric oxide production and cytotoxicity in cell. Conclusions:The findings suggest that the fresh Korean blueberry could be used as a source of natural antioxidants and anti-inflammatory agents.

Anti-cancer effect and apoptosis induction of cordycepin through DR3 pathway in the human colonic cancer cell HT-29.

Cordycepin is known to have many pharmacological effects such as anti-tumorigenic, anti-inflammatory and anti-angiogenic activity. However, cordycepin induced apoptosis through the DR3 pathway in human colon cancer cells has not been studied. The effect of cordycepin on anti-proliferation was investigated in this study. Cordycepin significantly inhibited cell viability in a dose and time-dependent manner. Cordycepin increased sub G1 and G2/M phase arrest on HT-29 cells at the concentration of 100 µM, whereas cordycepin at 200 µM and 400 µM increased G1 phase arrest. Cordycepin induced apoptosis in HT-29 cells in a dose-dependent manner as detected by Hoechst and Annexin V-FITC staining. Intracellular ROS levels were higher in cordycepin treated cells as compared to control cells. The protein related to apoptosis was determined by antibody array. p53 and Bax expression increased treatment with cordycepin for 18 h. DR3, caspase-8, caspase-1, cleaved caspase-3 and cleaved PARP expression increased. These finding suggest that the cordycepin induces apoptosis through the DR3 pathway in human colon cancer HT-29. These findings suggest that cordycepin should be evaluated further as a therapeutic agent in human colon cancer.

Anti-oxidant and anti-inflammatory activities of Inonotus obliquus and germinated brown rice extracts.

Inonotus obliquus (IO) is parasitic mushroom that grows on birch and other trees in Russia, Korea, Europe and United States. However, IO is not readily available for consumption due to its high cost and difficult growth. In this regard, IO was inoculated on germinated brown rice (GBR) in the present study and the antioxidant and anti-inflammatory activities of the IO grown on germinated brown rice (IOGBR) extracts were evaluated extensively and compared with those for IO and GBR. IOGBR showed highest antioxidant activities with scavenging total intracellular ROS and MDA levels as well as increasing the antioxidant enzymes activity in the H2O2-stimulated mice liver. It also exhibited best inflammatory activities by suppressing the proinflammatory mediators such as NO, PGE2, iNOS, COX-2, TNF-α, IL-1ß, and IL-6 in an LPS-stimulated RAW 264.7 cell line. This study provides a comparative approach to find out an excellent natural source of antioxidants and anti-inflammatory agent as a dietary supplement.

Natural products as a source of anti-inflammatory agents associated with inflammatory bowel disease.

Accumulating epidemiological and clinical study indicates that inflammation is a significant risk factor to develop various human diseases such as inflammatory bowel disease (IBD), chronic asthma, rheumatoid arthritis, multiple sclerosis, and psoriasis. Suppressing inflammation is therefore important to control or prevent various diseases. Among them, IBD is one of the major problems affecting people worldwide. IBD affects at least one in a thousand persons in many Western countries. Various natural products have been shown to safely suppress pro-inflammatory pathway and control IBD. In vivo and/or in vitro studies indicate that anti-IBD effects of natural products occur by inhibition of the expression of pro-inflammatory cytokines (for example, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule expression and pro-inflammatory mediators (such as inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2), master transcription factors (such as nuclear factor-κB (NF-κB)), reactive oxygen species (ROS) and by improving the antioxidant activity. In this review, we summarize recent research focused on IBD and the effects that natural products have on IBD factors.