Combination of red ginseng and velvet antler extracts prevents skin damage by enhancing the antioxidant defense system and inhibiting MAPK/AP-1/NF-κB and caspase signaling pathways in UVB-irradiated HaCaT keratinocytes and SKH-1 hairless mice.

Background: Studies have reported that the combination of two or more therapeutic compounds at certain ratios has more noticeable pharmaceutical properties than single compounds and requires reduced dosage of each agent. Red ginseng and velvet antler have been extensively used in boosting immunity and physical strength and preventing diseases. Thus, this study was conducted to elucidate the skin-protective potentials of red ginseng extract (RGE) and velvet antler extract (VAE) alone or in combination on ultraviolet (UVB)-irradiated human keratinocytes and SKH-1 hairless mice. Methods: HaCaT cells were preincubated with RGE/VAE alone or in combination for 2 h before UVB (30 mJ/cm2) irradiation. SKH-1 mice were orally given RGE/VAE alone or in combination for 15 days before exposure to single dose of UVB (600 mJ/cm2). Treated cells and treated skin tissues were collected and subjected to subsequent experiments. Results: RGE/VAE pretreatment alone or in combination significantly prevented UVB-induced cell death, apoptosis, reactive oxygen species production, and DNA damage in keratinocytes and SKH-1 mouse skins by downregulating mitogen-activated protein kinases/activator protein 1/nuclear factor kappa B and caspase signaling pathways. These extracts also strengthened the antioxidant defense systems and skin barriers in UVB-irradiated HaCaT cells and SKH-1 mouse skins. Furthermore, RGE/VAE co-administration appeared to be more effective in preventing UVB-caused skin injury than these extracts used alone. Conclusion: Overall, these findings suggest that the consumption of RGE/VAE, especially in combination, offers a protective ability against UVB-caused skin injury by preventing inflammation and apoptosis and enhancing antioxidant capacity.

Brain-Derived Neurotrophic Factor (BDNF) Enhances Osteogenesis and May Improve Bone Microarchitecture in an Ovariectomized Rat Model.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has gained attention as a therapeutic agent due to its potential biological activities, including osteogenesis. However, the molecular mechanisms involved in the osteogenic activity of BDNF have not been fully understood. This study aimed to investigate the action of BDNF on the osteoblast differentiation in bone marrow stromal cells, and its influence on signaling pathways. In addition, to evaluate the clinical efficacy, an in vivo animal study was performed. METHODS: Preosteoblast cells (MC3T3-E1), bone marrow-derived stromal cells (ST2), and a direct 2D co-culture system were treated with BDNF. The effect of BDNF on cell proliferation was determined using the CCK-8 assay. Osteoblast differentiation was assessed based on alkaline phosphatase (ALP) activity and staining and the protein expression of multiple osteoblast markers. Calcium accumulation was examined by Alizarin red S staining. For the animal study, we used ovariectomized Sprague-Dawley rats and divided them into BDNF and normal saline injection groups. MicroCT, hematoxylin and eosin (H&E), and tartrate-resistant acid phosphatase (TRAP) stain were performed for analysis. RESULTS: BDNF significantly increased ALP activity, calcium deposition, and the expression of osteoblast differentiation-related proteins, such as ALP, osteopontin, etc., in both ST-2 and the MC3T3-E1 and ST-2 co-culture systems. Moreover, the effect of BDNF on osteogenic differentiation was diminished by blocking tropomyosin receptor kinase B, as well as inhibiting c-Jun N-terminal kinase and p38 MAPK signals. Although the animal study results including bone density and histology showed increased osteoblastic and decreased osteoclastic activity, only a portion of parameters reached statistical significance. CONCLUSIONS: Our study results showed that BDNF affects osteoblast differentiation through TrkB receptor, and JNK and p38 MAPK signal pathways. Although not statistically significant, the trend of such effects was observed in the animal experiment.

Anti-Inflammatory and Antioxidant Activities of Lipophilic Fraction from Liriope platyphylla Seeds Using Network Pharmacology, Molecular Docking, and In Vitro Experiments.

Antioxidant and anti-inflammatory mechanisms counteract the pathogenesis of chronic diseases, such as diabetes, aging, and cancer. Therefore, enhancing antioxidant and anti-inflammatory functions may help manage these pathological conditions. This study aimed to assess the antioxidant and anti-inflammatory potentials of lipophilic fraction of Liriope platyphylla seeds (LLPS) using network pharmacology, molecular docking, and in vitro experiments. Here GC-MS analysis tentatively identified forty-three lipophilic compounds in LLPS. LLPS exhibited powerful antioxidant activity, according to the results from chemical-based antioxidant assays on DPPH, ABTS+, superoxide anion, hydrogen peroxide, nitric oxide, and hydroxyl radicals scavenging, lipid peroxidation, reducing antioxidant powers, and total antioxidant capacity. Additionally, LLPS enhanced cellular antioxidant capacity by inhibiting reactive oxygen species formation and elevating antioxidant enzyme levels, including catalase and heme oxygenase-1. Moreover, LLPS attenuated inflammatory response by reducing nitric oxide secretion and downregulating the expression of inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-1ß in lipopolysaccharide-treated macrophages. Network pharmacology and molecular docking analyses showed that key compounds in LPPS, particularly phytosterols and fatty acid esters, exerted antioxidant and anti-inflammatory properties through regulating NFKB1, PTGS1, PTGS2, TLR4, PRKCA, PRKCD, KEAP1, NFE2L2, and NR1l2. Overall, these data suggest that LLPS may be a potential antioxidant and anti-inflammatory agent for developing functional foods.

Antioxidant and Anti-Inflammatory Mechanisms of Lipophilic Fractions from Polyscias fruticosa Leaves Based on Network Pharmacology, In Silico, and In Vitro Approaches.

Polyscias fruticosa leaf (PFL) has been used in food and traditional medicine for the treatment of rheumatism, ischemia, and neuralgia. However, the lipophilic components of PFL and their biological properties remain unknown. This study, integrating network pharmacology analysis with in silico and in vitro approaches, aimed to elucidate the antioxidant and anti-inflammatory capacities of lipophilic extracts from PFL. A total of 71 lipophilic compounds were identified in PFL using gas chromatography-mass spectrometry. Network pharmacology and molecular docking analyses showed that key active compounds, mainly phytosterols and sesquiterpenes, were responsible for regulating core target genes, such as PTGS2, TLR4, NFE2L2, PRKCD, KEAP1, NFKB1, NR1l2, PTGS1, AR, and CYP3A4, which were mostly enriched in oxidative stress and inflammation-related pathways. Furthermore, lipophilic extracts from PFL offered powerful antioxidant capacities, as evident in our cell-free antioxidant assays. These extracts also provided a protection against oxidative stress by inducing the expression of catalase and heme oxygenase-1 in lipopolysaccharide (LPS)-treated RAW 264.7 cells. Additionally, lipophilic fractions from PFL showed anti-inflammatory potential in downregulating the level of pro-inflammatory factors in LPS-treated macrophages. Overall, these findings provide valuable insights into the antioxidant and anti-inflammatory properties of lipophilic extracts from PFL, which can be used as a fundamental basis for developing nutraceuticals and functional foods.

Red ginseng dietary fiber promotes probiotic properties of Lactiplantibacillus plantarum and alters bacterial metabolism.

Korean red ginseng has been widely used as an herbal medicine. Red ginseng dietary fiber (RGDF) is a residue of the processed ginseng product but still contains bioactive constituents that can be applied as prebiotics. In this study, we evaluated changes on fermentation profiles and probiotic properties of strains that belong to family Lactobacillaceae with RGDF supplementation. Metabolomic analyses were performed to understand specific mechanisms on the metabolic alteration by RGDF and to discover novel bioactive compounds secreted by the RGDF-supplemented probiotic strain. RGDF supplementation promoted short-chain fatty acid (SCFA) production, carbon source utilization, and gut epithelial adhesion of Lactiplantibacillus plantarum and inhibited attachment of enteropathogens. Intracellular and extracellular metabolome analyses revealed that RGDF induced metabolic alteration, especially associated with central carbon metabolism, and produced RGDF-specific metabolites secreted by L. plantarum, respectively. Specifically, L. plantarum showed decreases in intracellular metabolites of oleic acid, nicotinic acid, uracil, and glyceric acid, while extracellular secretion of several metabolites including oleic acid, 2-hydroxybutanoic acid, hexanol, and butyl acetate increased. RGDF supplementation had distinct effects on L. plantarum metabolism compared with fructooligosaccharide supplementation. These findings present potential applications of RGDF as prebiotics and bioactive compounds produced by RGDF-supplemented L. plantarum as novel postbiotic metabolites for human disease prevention and treatment.

Investigation of phenyllactic acid as a potent tyrosinase inhibitor produced by probiotics.

Melanogenesis is responsible for skin pigmentation and the enzymatic browning of foods. Tyrosinases play a major role in melanin synthesis, and many attempts have been made to identify new natural tyrosinase inhibitors, but few have sought to do in microbes. Postbiotics are bioactive compounds produced by the metabolism of probiotics and have been reported to be safe and effective. In this study, we evaluated the tyrosinase inhibitory effects of culture supernatants of probiotics and discovered novel bacterial metabolites that can be used as a potent tyrosinase inhibitor based on metabolomics. Cultures of Bifidobacterium bifidum IDCC 4201 and Lactiplantibacillus plantarum IDCC 3501 showed effective anti-tyrosinase, reduced melanin synthesis, and altered protein expression associated with the melanogenesis pathway. Comparative metabolomics analyses conducted by GC-MS identified metabolites commonly produced by B. bifidum and L. plantarum. Of eight selected metabolites, phenyllactic acid exhibited significant tyrosinase-inhibitory activity. Our findings suggest that applications of probiotic culture supernatants containing high amounts of phenyllactic acid have potential use as anti-melanogenesis agents in food and medicines.

Hair Growth-Promoting Effects of Rosehip (Rosa canina L.) Seed Oil in C57BL/6 Mice.

Rosehip (Rosa canina L.) seeds, a by-product of the food processing industry, contain various bioactive compounds that have potential cosmetic and pharmacological applications. Rosehip seed oil (RHSO) has been shown to exert therapeutic effects in skin disorders, but its role in promoting hair growth remains unknown. In this study, we aimed to elucidate the hair growth-promoting activity of RHSO and the related mechanisms of action. The depleted dorsal skin of telogenic C57BL/6 mice was topically treated with RHSO for 21 days, and the extent of hair regrowth was assessed. The results indicated that RHSO stimulated hair growth by inducing the early transition of hair follicles from telogen to anagen phase. Histological analysis revealed significant increases in hair follicle density, hair bulb size, and skin thickness. RHSO treatment also upregulated the expression of hair growth-associated genes, including ß-catenin, phospho-glycogen synthase kinase-3 beta, Sonic hedgehog, smoothened, cyclin D1, cyclin E, and insulin like growth factor 1. These findings suggest that RHSO stimulates hair growth and may show promise as a preventive and/or therapeutic agent for hair loss.

Phytochemical Composition and Antioxidant and Anti-Inflammatory Activities of Ligularia fischeri Turcz: A Comparison between Leaf and Root Extracts.

Ligularia fischeri Turcz leaves are widely consumed and have multiple health benefits. We aimed to evaluate the differences in the phytochemical composition and biological properties of the root and leaf extracts from L. fischeri. The root extract exhibited higher antioxidant capacity and total flavonoid levels than the leaf extract. GC/MS analysis revealed the presence of various volatiles, diterpenoids, sesquiterpenes, and other non-polar compounds. Moreover, these extracts enhanced cellular antioxidant defense by reducing the level of reactive oxygen species and upregulating the expression of catalase and heme oxygenase-1 in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The root and leaf extracts also exerted anti-inflammatory effects by suppressing nitric oxide production and diminishing the levels of inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-1ß in LPS-stimulated macrophages. Overall, these findings suggest that L. fischeri root extract contains diverse bioactive compounds for the development of nutraceuticals or functional foods with antioxidant and anti-inflammatory activity.

Protective Effects of Orange Sweet Pepper Juices Prepared by High-Speed Blender and Low-Speed Masticating Juicer against UVB-induced Skin Damage in SKH-1 Hairless Mice.

Sweet pepper fruits (Capsicum annuum L.) contain various nutrients and phytochemicals that enhance human health and prevent the pathogenesis of certain diseases. Here, we report that oral administration of orange sweet pepper juices prepared by a high-speed blender and low-speed masticating juicer reduces UVB-induced skin damage in SKH-1 hairless mice. Sweet pepper juices reduced UVB-induced skin photoaging by the regulation of genes involved in dermal matrix production and maintenance such as collagen type I α 1 and matrix metalloproteinase-2, 3, 9. Administration of sweet pepper juices also restored total collagen levels in UVB-exposed mice. In addition, sweet pepper juices downregulated the expression of pro-inflammatory proteins such as cyclooxygenase-2, interleukin (IL)-1ß, IL-17, and IL-23, which was likely via inhibiting the NF-κB pathway. Moreover, primary antioxidant enzymes in the skin were enhanced by oral supplementation of sweet pepper juices, as evidenced by increased expression of catalase, glutathione peroxidase, and superoxide dismutase-2. Immunohistochemical staining showed that sweet pepper juices reduced UVB-induced DNA damage by preventing 8-OHdG formation. These results suggest that sweet pepper juices may offer a protective effect against photoaging by inhibiting the breakdown of dermal matrix, inflammatory response, and DNA damage as well as enhancing antioxidant defense, which leads to an overall reduction in skin damage.

Red ginseng (Panax ginseng Meyer) oil: A comprehensive review of extraction technologies, chemical composition, health benefits, molecular mechanisms, and safety.

Red ginseng oil (RGO), rather than the conventional aqueous extract of red ginseng, has been receiving much attention due to accumulating evidence of its functional and pharmacological potential. In this review, we describe the key extraction technologies, chemical composition, potential health benefits, and safety of RGO. This review emphasizes the proposed molecular mechanisms by which RGO is involved in various bioactivities. RGO is mainly produced using organic solvents or supercritical fluid extraction, with the choice of method greatly affecting the yield and quality of the end products. RGO contains a high unsaturated fatty acid levels along with considerable amounts of lipophilic components such as phytosterols, tocopherols, and polyacetylenes. The beneficial health properties of RGO include cellular defense, antioxidation, anti-inflammation, anti-apoptosis, chemoprevention, hair growth promotion, and skin health improvement. We propose several molecular mechanisms and signaling pathways that underlie the bioactivity of RGO. In addition, RGO is regarded as safe and nontoxic. Further studies on RGO must focus on a deeper understanding of the underlying molecular mechanisms, composition-functionality relationship, and verification of the bioactivities of RGO in clinical models. This review may provide useful information in the development of RGO-based products in nutraceuticals, functional foods, and functional cosmetics.

Hair Growth-Promoting Mechanisms of Red Ginseng Extract through Stimulating Dermal Papilla Cell Proliferation and Enhancing Skin Health.

This study aimed to investigate the underlying mechanisms of red ginseng extract (RGE) on regulating hair growth and hair follicle development. Results from in vitro studies showed that RGE treatment simultaneously enhanced viability and inhibited apoptosis in human hair dermal papilla cells. Moreover, RGE administration promoted telogen-to-anagen transition, prolonged anagen in hair follicular cycling, and increased the size of hair follicles and skin thickness in a C57BL/6 mouse model. Furthermore, RGE treatment significantly upregulated the expression of ß-catenin, phospho-glycogen synthase kinase 3ß, cyclin D1, cyclin E, and Bcl-2, phospho-extracellular signal-regulated protein kinase, and phospho-Akt, which are associated with promoting hair growth. In addition, RGE enhanced skin health by activation of antiox-idant defense systems. Our data demonstrates that hair regenerative mechanisms of RGE may be mediated by stimulating dermal papilla cell proliferation and enhancing skin functions.

Cellular Defensive Mechanisms of Tea Polyphenols: Structure-Activity Relationship.

Tea is particularly rich in polyphenols, including catechins and theaflavins, thearubigins, flavonols, and phenolic acids, which are believed to contribute to the health benefits of tea. The health-promoting effects of tea polyphenols are believed to be related to their cellular defensive properties. This review is intended to briefly summarize the relationship between the chemical structures of tea polyphenols and their biological activities. Tea polyphenols appear as direct antioxidants by scavenging reactive oxygen/nitrogen species; chelating transition metals; and inhibiting lipid, protein, and DNA oxidations. They also act directly by suppressing "pro-oxidant" enzymes, inducing endogenous antioxidants, and cooperating with vitamins. Moreover, tea polyphenols regulate cellular signaling transduction pathways, importantly contributing to the prevention of chronic diseases and the promotion of physiological functions. Apparently, the features in the chemical structures of tea polyphenols are closely associated with their antioxidant potentials.

Phytochemical and Over-The-Counter Drug Interactions: Involvement of Phase I and II Drug-Metabolizing Enzymes and Phase III Transporters.

Consumption of plant-derived natural products and over-the-counter (OTC) drugs is increasing on a global scale, and studies of phytochemical-OTC drug interactions are becoming more significant. The intake of dietary plants and herbs rich in phytochemicals may affect drug-metabolizing enzymes (DMEs) and transporters. These effects may lead to alterations in pharmacokinetics and pharmacodynamics of OTC drugs when concomitantly administered. Some phytochemical-drug interactions benefit patients through enhanced efficacy, but many interactions cause adverse effects. This review discusses possible mechanisms of phytochemical-OTC drug interactions mediated by phase I and II DMEs and phase III transporters. In addition, current information is summarized for interactions between phytochemicals derived from fruits, vegetables, and herbs and OTC drugs, and counseling is provided on appropriate and safe use of OTC drugs.

Red ginseng oil promotes hair growth and protects skin against UVC radiation.

BACKGROUND: A wide range of environmental factors, such as diseases, nutritional deficiencies, ageing, hormonal imbalances, stress, and ultraviolet (UV) radiation, may affect the structure and function of the skin that covers the entire surface of the human body. In this study, we investigated roles of red ginseng oil (RGO) in enhancing skin functions, including hair growth and skin protection, using mouse models. METHODS: For hair growth experiment, shaved dorsal skins of C57BL/6 mice were topically applied with vehicle, RGO, RGO's major compounds, or minoxidil for consecutive 21 days and skin tissues were examined the hair growth promoting capacity. For skin protection experiment, SKH-1 hairless mice were topically applied with vehicle or RGO twice a day for three days prior to exposure to UVC radiation at 20 kJ/cm2. Skin tissues were collected to evaluate skin protective effects of RGO. RESULTS: Topical application of RGO to C57BL/6 mice effectively promoted hair regeneration by inducing early telogen-to-anagen transition and significantly increasing the density and bulb diameter of hair follicles. Major compounds, including linoleic acids and ß-sitosterol, contributed to RGO-promoted hair growth. Treatment with RGO as well as its major components upregulated expression of hair growth-related proteins. Furthermore, in SKH-1 hairless mice, RGO had a protective effect against UVC-induced skin damage by inhibiting inflammation and apoptosis, as well as inducing cytoprotective systems. CONCLUSION: These data suggest that RGO may be a potent agent for improving skin health and thereby preventing and/or treating hair loss and protecting skin against UV radiation.

Antioxidant and Anti-Inflammatory Activities of Zingiber montanum Oil in HepG2 Cells and Lipopolysaccharide-Stimulated RAW 264.7 Macrophages.

Improvement of antioxidant and anti-inflammatory functions is believed to be an effective strategy for protection against various diseases such as cancer, aging, and neurodegenerative disease. This study focused on investigating antioxidant and anti-inflammatory abilities of Zingiber montanum oil (ZMO) extracted by the supercritical CO2 fluid system in HepG2 cells and lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Ten predominant constituents of ZMO were identified, in which triquinacene, 1,4-bis (methoxy), terpinen-4-ol, triquinacene, 1,4,7-tris (methoxy), α-terpinene, sabinene hydrate, and (E and Z)-1-(3,4-dimethoxyphenyl)butadiene account for 86.47%. ZMO exhibited anti-inflammatory capacity by inhibiting the formation of pro-inflammatory markers such as nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, interleukin (IL)-1ß, IL-6, and monocyte chemoattractant protein-1 in LPS-treated macrophages. The LPS-induced stimulation of nuclear factor-kappa B, signal transducer and activator of transcription 3 (Stat3) and mitogen-activated protein kinase (MAPK) pathways as evident from increased phosphorylation of IKKα/ß, IκBα, p65, Stat3, ERK, JNK, and p38 MAPK was also suppressed by ZMO pretreatment. Further, ZMO enhanced the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1), and concurrently, reduced intracellular reactive oxygen species accumulation in LPS-treated RAW 264.7 cells. In addition, ZMO treatment markedly upregulated the expression of Nrf2 as well as its target genes, HO-1 and NAD(P)H:quinone oxidoreductase 1 in HepG2 cells. These data propose that ZMO may be a potent candidate for prevention and/or treatment of inflammatory and oxidative conditions.

RAS/RAF mutations and their associations with epigenetic alterations for distinct pathways in Vietnamese colorectal cancer.

KRAS, NRAS, and BRAF are potential tumor-driven genes that are involved in the RAS/RAF/MAPK signaling pathway. RAS/RAF mutations importantly contribute to colorectal tumorigenesis since they remain the activated status of downstream pathways without regulation of the upstream EGFR signal. However, it has not been unclear how epigenetic alterations involved in colorectal tumorigenesis mediated by KRAS, NRAS, or BRAF mutations. Therefore, in this study, we investigated the frequency and distribution of KRAS/NRAS/BRAF mutations in Vietnamese colorectal cancer (CRC) and explored the relationship between genetic and epigenetic abnormalities in 156 tumors of CRC. Somatic mutations of KRAS (exon 2, codon 12/13; exon 3, codon 61), NRAS (exon 2, codon 12/13; exon 3, codon 61), and BRAF (exon 15, codon 600) was determined by Cobas® KRAS Mutation Test, Therascreen NRAS Pyro Kit and Cobas® 4800 BRAF V600 Mutation Test, respectively. Methylation status of BRCA1, MLH1, MGMT, p16, RASSF1A, and APC was detected by methylation-specific PCR. Distribution of each abnormality in clinicopathological features was also analyzed. Results showed the mutation rates of KRAS, NRAS, and BRAF were 41.0 %, 9.6 %, 8.3 % respectively, while the methylation rates of BRCA1, MLH1, MGMT, p16, RASSF1A, and APC were 16.7 %, 16.7 %, 32.7 %, 30.1 %, 30.1 %, and 37.2 % respectively. The distribution of KRAS mutation was mutually exclusive against that of NRAS (p < 0.001) and BRAF (p < 0.001) mutations in CRC. RAS/RAF mutations were more common in adenocarcinoma subtype (p = 0.020), whereas RASSF1A methylation was more frequent in mucinous adenocarcinoma subtype (p = 0.007). In addition, the frequency of having KRAS mutations was significantly higher in MGMT (p = 0.035) or RASSF1A (p = 0.043) methylated cases than in those without methylation. BRAF mutations were positively associated with MLH1 hypermethylation (p = 0.028) but were inversely associated with APC hypermethylation (p = 0.032). Overall, our results show specific interactions of genetic and epigenetic alterations and suggest the presence of independent oncogenic pathways in tumorigenesis of CRC.

Human Papillomavirus Infection, p16INK4a Expression and Genetic Alterations in Vietnamese Cervical Neuroendocrine Cancer.

Neuroendocrine cervical cancer is a rare subtype of cervical cancer with a highly aggressive malignancy. This study was conducted to analyse the human papillomavirus (HPV) infection and molecular abnormalities in Vietnamese neuroendocrine carcinomas of the uterine cervix. HPV genotyping and p53 mutations were examined using polymerase chain reaction (PCR)-based direct sequencing. Mutations of epidermal growth factor receptor (EGFR), Kirsten rat sarcoma (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B (BRAF) were identified using commercial kits. Four high-risk HPV genotypes were identified in 26 (86.7%) out of a total of 30 tumours. The prevalence of HPV 16, 18, 31 and 45 was 20.0%, 50.0%, 20.0% and 36.7%, respectively. Overexpression of p16INK4a was observed in 93.3% of cases and was significantly correlated with high-risk HPV infections. Furthermore, p53 and NRAS mutations were detected in five (16.7%) and one (3.3%) cases, respectively, whereas no EGFR, KRAS or BRAF mutations were observed. These results demonstrate that high-risk HPV infection may be an important oncogenic factor for the development and progression of cervical neuroendocrine carcinoma.

Anti-inflammatory and anti-oxidant effects of combination between sulforaphane and acetaminophen in LPS-stimulated RAW 264.7 macrophage cells.

Objectives: Accumulating evidence indicates that combination of therapeutic agents may increase their pharmacological properties with fewer undesired side effects. Acetaminophen (APAP) has been widely used to treat pain and fever in many countries. However, APAP only possesses a weak anti-inflammatory property at therapeutic dose, and exhibits hepatotoxicity at high dose. On other hand, sulforaphane (SFN) has been well-known as a potential anti-inflammatory and antioxidant agent. In this study, we investigated the anti-inflammatory and antioxidant effects of combination between APAP and SFN in LPS-stimulated RAW 264.7 macrophage cells. Methods: Nitric oxide (NO) assay was determined using the Griess assay. Reactive oxygen species (ROS) formation was measured using an ROS-sensitive fluorescence indicator, DCFH-DA. The protein expression was determined by western blot analysis. Results: Our results showed that the combination of SFN and APAP exhibited an inhibitory effect on inflammatory markers such as NO, iNOS, COX-2, and IL-1ß, and this effect was more pronounced than the compound was used alone. In addition, the combination of SFN and APAP at low doses decreased intracellular ROS formation and increased the protein levels of CAT, GPx, Nrf2, NQO1, and HO-1, which were much better than APAP alone and were equivalent to SFN at full dose. Conclusions: Our findings suggest that the combination of APAP and SFN enhanced anti-inflammatory and anti-oxidant activities in stimulated macrophages, which provide an important rationale to utilize drug and food in combination for prevention and/or treatment inflammation-related diseases.

Chemopreventive Activity of Red Ginseng Oil in a Mouse Model of Azoxymethane/Dextran Sulfate Sodium-Induced Inflammation-Associated Colon Carcinogenesis.

Our previous studies have demonstrated antioxidant and cytoprotective properties of red ginseng oil (RGO). However, the role of RGO in models of intestinal inflammation has not been elucidated. In this study, we evaluated the chemopreventive effect of RGO in a mouse model of azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis and explored its underlying mechanisms. Male C57BL/6 mice were intraperitoneally injected with a single dose of AOM (10 mg/kg), followed by 1.5% DSS in drinking water for 7 days to produce colon carcinogenesis. RGO at 10 or 100 mg/kg was orally given for 17 weeks. RGO supplementation reduced the plasma nitric oxide (NO) concentration as well as lipid peroxidation and inhibited the production of proinflammatory factors such as inducible NO synthase, cyclooxygenase-2, interleukin 1ß, IL-6, and tumor necrosis factor-α in the mouse colitis tissue. Increased phosphorylation levels of p65 and IκB by AOM/DSS exposure were attenuated by the presence of RGO. In addition, RGO supplementation induced the activity of primary antioxidant enzymes such as superoxide dismutase and catalase as well as the expression of nuclear factor erythroid 2-related factor 2-mediated antioxidant enzyme hemeoxygenase-1 in the colons of AOM/DSS-treated mice. These findings indicate that RGO may be a potent natural chemopreventive agent for ameliorating inflammatory bowel diseases.

Genetic and epigenetic alterations of the EGFR and mutually independent association with BRCA1, MGMT, and RASSF1A methylations in Vietnamese lung adenocarcinomas.

Genetic and epigenetic alterations importantly contribute to the pathogenesis of lung cancer. In the study, we measured the frequency and distribution of molecular abnormalities of EGFR as well as the aberrant promoter methylations of BRCA1, MGMT, MLH1, and RASSF1A in Vietnamese lung adenocarcinomas. We investigated the association between genetic and epigenetic alteration, and between each abnormality with clinicopathologic parameters. Somatic EGFR mutation that was found in 49/139 (35.3%) lung adenocarcinomas showed a significant association with young age, female gender, and non-smokers. EGFR overexpression was identified in 82 tumors (59.0%) and statistical relationships with EGFR or BRCA1 methylation but not EGFR mutation. In addition, EGFR, BRCA1, MGMT, MLH1, and RASSF1A methylations were found in 33 (23.7%), 41 (29.5%), 46 (33.1%), 28 (20.1%), and 41 (29.5%) cases of a total of 139 lung adenocarcinomas, respectively. The RASSF1A methylation was found to be linked to the smoking habit. Methylations in MGMT and RASSF1A were also found to correlate with metastasis status. Furthermore, the distribution of EGFR mutation and that of BRCA1, MGMT or RASSF1A methylation were significantly exclusive in lung adenocarcinomas. The main finding of our study demonstrate that epigenetic abnormalities might play a critical role for the lung tumorigenesis in patients with smoking history and metastasis, and partly affect the predictive value of EGFR mutations through blocking expression due to promoter EGFR hypermethylation. Mutually exclusive distribution of genetic and epigenetic alterations reflects differently biological characteristics in the etiology of lung adenocarcinomas.