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Sesamin Enhances Nrf2-Mediated Protective Defense against Oxidative Stress and Inflammation in Colitis via AKT and ERK Activation
Ulcerative colitis (UC) is a major form of inflammatory bowel disease (IBD) with high incidence and prevalence in many countries. Patients with UC usually suffer from a lifetime of debilitating physical symptoms. Therefore, developing effective therapeutic strategy that can manage this disease better and improve patients’ life quality is in urgent need. Sesamin (SSM) is a lignan derived from sesame seeds. In this study, the protective effect of SSM against UC and the underlying mechanism were investigated in vitro and in vivo. Our data showed that SSM protected Caco-2 cells from H2O2-induced oxidative stress injury via GSH-mediated scavenging of reactive oxygen species (ROS). Dual luciferase reporter assay showed that the transcriptional activity of nuclear factor erythroid-related factor 2 (Nrf2) was significantly increased by SSM, and the ability of SSM to activate Nrf2-targeted genes was further confirmed in Caco-2 cells using western blot and quantitative real-time PCR (qRT-PCR). In contrast, Nrf2 knockdown abolished the protective effect of SSM. Additionally, we found that SSM also activated advanced protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) in Caco-2 cells, while either AKT or ERK inhibition can prevent SSM-mediated nuclear translocation of Nrf2. Furthermore, SSM displayed a better protective effect against dextran sulfate sodium- (DSS-) induced UC compared with 5-aminosalicylic acid (5-ASA) in C57BL/6 mice. The enhanced Nrf2 signaling and activated AKT/ERK were also observed in the colon of mice after SSM administration. These results first demonstrate the protective effect of SSM against UC and indicate that the effect is associated with AKT/ERK activation and subsequent Nrf2 signaling enhancement. This study provides a new insight into the medicinal value of SSM and proposes it as a new natural nutrition for better managing the symptoms of UC.
Ulcerative colitis (UC) is a major form of inflammatory bowel disease (IBD). The disease is associated with a lifetime of debilitating physical symptoms, such as vomiting, anorexia, urgent diarrhea, and rectal bleeding, at an incidence of 1/200 people from developed countries . Similar situations can be also found in many developing countries in which the incidence and prevalence of UC were on the rise for the past few years . Therefore, finding effective therapeutic strategies that can manage this disease better and improve the quality of patients’ life is in urgent need.
Although the mechanism underlying UC is not fully understood, increasing experimental and clinical evidence indicated that oxidative stress plays an important role in the development of colitis [3, 4]. Diffusive inflammatory cell infiltration and small intestinal mucosal crypt abscesses in colitis trigger the overproduction of reactive oxygen species (ROS), which causes oxidative stress damage to colon cells and epithelial barrier permeability, leading to pathogen invasion and exaggeration of inflammatory cell infiltration and inflammatory damage . Therefore, antioxidant prevention and ROS-targeted treatment were proposed in many studies to alleviate colitis [3, 6].
Nuclear factor erythroid-related factor 2 (Nrf2) is a redox-sensitive transcription factor which plays an essential role in protection against oxidative stress and electrophilic injury by regulating a battery of cytoprotective genes, such as NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase 1 (HO-1), and glutamate-cysteine ligase (GCL) . Electrophilic and oxidative stressors, such as ROS, can activate Nrf2 through dissociating it from Kelch-like ECH-associated protein-1 (Keap1) or promoting its phosphorylation by several kinases, including advanced protein kinase B (AKT), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (P38), and protein kinase C (PKC) [8–11]. The activated Nrf2 is guided into the nucleus and then binds to the antioxidant responsive element (ARE) with small Maf protein (sMaf) to initiate the transcription of downstream cytoprotective genes to defend various oxidative and oncogenic stressors . Recently, a role of Nrf2 in protection against colitis and inflammation-associated colon cancer was revealed. For instance, Nrf2-deficient mice were more susceptive to dextran sulfate sodium- (DSS-) induced colitis or colorectal cancer than wild-type mice [13, 14]. Activation of Nrf2-regulated genes effectively alleviated the inflammatory response in mouse colitis, while inhibition of these genes enhanced inflammatory response to oxidative stress [15, 16]. Additionally, several genetic mutations on Nrf2 were found to be associated with the susceptibility and progression of DSS-induced colitis in mice . These findings make Nrf2 signaling pathway an attractive target to combat UC.
Sesamin (SSM) is a lignan derived from sesame seeds (Figure 1(a) shows the chemical structure of SSM) . It is catered to be a nutritional supplement because of its antioxidative and anti-inflammatory effects. It was reported that SSM can inhibit lipopolysaccharide- (LPS-) induced inflammation and extracellular matrix catabolism in a rat intervertebral disc . Similarly, SSM can attenuate LPS-induced acute oxidative stress injury in the lung or liver of mice by inhibiting the Toll-like receptor 4 signaling pathway [20, 21]. Furthermore, SSM was reported to protect against LPS or 1-methyl-4-phenyl-pyridine-induced nerve injuries by inhibiting the production of nitric oxide and cytokine [22, 23]. Through alleviating high mobility group box 1- (HMGB1-) dependent inflammatory response, SSM can protect human endothelial cells from HMGB1-induced vascular inflammatory diseases . However, the protective effect of SSM on UC and the underlying mechanism have not been investigated yet.
In the present study, we evaluated the protective effect of SSM against UC and investigated the underlying mechanism in vivo and in vitro. Our results demonstrate for the first time that SSM can significantly enhance Nrf2-mediated protective defense against colitis in an AKT- or ERK-dependent manner. This study may provide a potential therapeutic strategy for IBD treatment and make SSM an attractive candidate to combat UC.
2. Material and Methods
2.1. Reagents and Chemicals
SSM (), DSS (MW ~40 kDa), L-buthionine-sulfoximine (BSO) (), PD98059 (), wortmannin (), L-sulforaphane (SFN) (), and 5-aminosalicylic acid (5-ASA) () were obtained from Sigma-Aldrich (St. Louis, USA). 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and dimethyl sulfoxide (DMSO) were from MP Biomedicals (CA, USA). Primary rabbit antibodies against Nrf2 (12721), Keap1 (8047), ERK1/2 (4695), p38 (8690), PKCα (59754), AKT (4685), p-p38 (Thr180/Tyr182) (4511), p-ERK1/2 (Thr202/Tyr204) (8544), p-AKT (Thr308) (13038), HO-1 (5853), lamin B (15068), and GAPDH (5174) were obtained from Cell Signaling Technology (MA, USA). Primary rabbit antibodies against NQO1 (GTX30626), GCLM (GTX53719), GCLC (GTX113197), and GR (GTX114199) were from GeneTex (Texas, USA). Primary rabbit antibody against p-PKCα (Thr638) (44-962G) was bought from Thermo Fisher Scientific (NH, USA). Goat anti-rabbit IgG antibody (D111018) was purchased from Sangon Biotech (Shanghai, China). Other chemicals were of analytical grade from commercial suppliers.
2.2. Cell Lines and Cell Culture
Human embryonic kidney HEK293T cells and colorectal adenocarcinoma Caco-2 cells were obtained from the Cell Bank of Shanghai Institute of Biochemistry and Cell Biology (Shanghai, China). HEK293T cells were cultured in Dulbecco’s modified Eagle medium (DMEM, HyClone, UT, USA), supplemented with 10% fetal bovine serum (FBS, Gibco, NY, USA) and 1% antibiotic-antimycotic solution (HyClone, UT, USA). Caco-2 cells were cultured in DMEM supplemented with 12% fetal bovine serum, 1% non-essential amino-acid, and 1% antibiotic-antimycotic solution. Cell lines were cultured in a humidified atmosphere with 5% CO2 at 37°C.
2.3. Cytotoxicity Assay
Caco-2 cells in a logarithmic phase were seeded in a 96-well plate at the density of per well. After incubation for 12 h, cells were treated with selected concentrations of H2O2 (prepared in autoclaved water), SSM (prepared in DMSO), BSO (prepared in autoclaved water), PD98059 (prepared in DMSO), wortmannin (prepared in DMSO), and SFN (prepared in DMSO) for the indicated time. Then, 20 μl of MTT solution (5 mg/ml, dissolved in PBS) was added to each well, and the cells were incubated for 4 h in a humidified atmosphere with 5% CO2 at 37°C. Finally, 150 μl DMSO was added to each well to dissolve formazan, and the plate was shaken at room temperature for 10 min. The absorbance of each well was detected using a Multiskan Spectrum Microplate Reader (Thermo Fisher Scientific, NH, USA; OD 570 nm). [SSM was initially prepared in DMSO to different concentrations (10, 20, 40, 80, 160, and 320 mM) and then mixed with culture medium at the dilution ratio of 1 : 1000 for cell treatment. Other DMSO-dissolved chemicals were prepared in the same way, and therefore, cells treated with culture medium with 0.1% DMSO should be used as the control for these experiments].
2.4. Dual Luciferase Reporter Assay
Cells were seeded in 96-well plates and incubated for 12 h. Plasmids (pEF-Nrf2, pGL3-ARE, and pRL-TK) were gifts from Dr. Zhiying Huang (School of Pharmaceutical Sciences, Sun Yat-sen University, China). The pEF-Nrf2 (Nrf2 expression plasmid) was constructed by cloning a 2.5 kb BamHI-NotI fragment containing human Nrf2 cDNA into a pEF1a-V5 vector (Invitrogen, NY, USA). The pGL3-ARE reporter was constructed by cloning a SacI-XhoI fragment containing a synthetic oligonucleotide (distal ARE of the human GCS heavy chain synthetase gene promoter) into the pGL3 promoter (Promega, WI, USA). The pRL-TK reporter was constructed by cloning a cDNA encoding Renilla luciferase into the pRL reporter vectors (Promega, WI, USA). pEF-Nrf2 and pGL3-ARE (transfection ratio is 1 : 2) were cotransfected with pRL-TK (internal control) into the cells using Lipofectamine® 2000 (Invitrogen, NY, USA) according to the manufacturer’s protocol. After transfection for 6 h, cells were treated with SSM for 8, 16, and 24 h and then lysed for the detection of luciferase activity using a Dual Luciferase Reporter Gene Assay Kit (Promega, WI, USA) and luminometer Lumat LB 9507 (Berthold Technologies, Bad Wildbad, Germany) according to the manufacturer’s instructions. Finally, the transcriptional activity of Nrf2 was calculated through dividing the Firefly luciferase activity by the Renilla luciferase activity.
2.5. RNA Isolation and Quantitative Real-Time PCR (qRT-PCR)
Caco-2 cells were seeded in 12-well plates for overnight incubation and then treated with different concentrations of SSM for 8, 16, and 24 h. After that, cells were washed with 1× PBS twice, and total cellular RNA was isolated by using a TRIzol® reagent (Takara, Tokyo, Japan). cDNA was prepared using a PrimeScript™ RT Reagent Kit (Takara, Tokyo, Japan). QRT-PCR was performed in a 7500 Real-Time PCR System (Applied Biosystems, CA, USA) using SYBR® Premix Ex Taq™ II (Tli RNaseH Plus) (Takara, Tokyo, Japan). The primers used in this study were synthetized by Invitrogen (Thermo Fisher Scientific, NH, USA) and are listed in Supplementary table 1. GAPDH and β-actin were used as internal controls. Fold changes were calculated for each treatment group versus the control group using the Pfaffl method.
2.6. Western Blot
Caco-2 cells were seeded in 6-well plates for overnight incubation and then treated with various concentrations of SSM, PD98059, and wortmannin for indicated times. After that, cells were washed with 1× PBS twice, and total or nuclear protein was extracted using a Protein Extraction Kit (Beyotime, Shanghai, China) according to the product’s specification. Protein samples (30 μg) were separated by 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to 0.45 μm PVDF membranes (Millipore, MA, USA). After blocking with 5% BSA for 1 h, the membranes were incubated with primary antibodies, including anti-Nrf2 (1 : 1000 dilution), anti-Keap1 (1 : 1000 dilution), anti-HO-1 (1 : 1000 dilution), anti-NQO1 (1 : 1000 dilution), anti-GCLM (1 : 1000 dilution), anti-GCLC (1 : 1000 dilution), anti-GR (1 : 1000 dilution), anti-p38 (1 : 1000 dilution), anti-p-p38 (1 : 1000 dilution), anti-PKCα (1 : 1000 dilution), anti-p-PKCα (1 : 1000 dilution), anti-ERK1/2 (1 : 1000 dilution), anti-p-ERK1/2 (1 : 1000 dilution), anti-AKT (1 : 1000 dilution), anti-p-AKT (1 : 1000 dilution), anti-GAPDH (1 : 1000 dilution), and anti-lamin B (1 : 1000 dilution), overnight at 4°C, and then incubated with secondary antibodies at room temperature for 1 h. An ECL kit (Engreen Biosystem, Beijing, China) was employed to detect chemiluminescence. The intensity of protein bands was analyzed by ImageJ (NIH Image, MD, USA). GAPDH and lamin B were used as loading controls for total fraction and nuclear fraction, respectively.
2.7. Detection of ROS
Intracellular ROS were detected using DCFH-DA fluorescence assay. Specifically, Caco-2 cells were seeded in a 96-well plate at a density of per well. Cells were treated with selected concentrations of H2O2, SSM, PD98059, and wortmannin for the indicated times. Then, 100 μl DCFH-DA solution (DCFH-DA:1× PBS, 1 : 1000) was added into each well. After incubation for 20 min, cells were washed with 1× PBS three times. Photos were taken using an Inverted Fluorescence Microscope (OLYMPUS IX73, Tokyo, Japan). At least 50 unique areas of view were taken and analyzed for each representative photo. Fluorescence intensity was analyzed using a Flex Station 3 Multifunctional Microplate Reader (Molecular Devices, CA, USA). The percentage of positive cells was calculated by Image-Pro® Plus 6.0 (Media Cybernetics, MD, USA) according to the following formula: .
2.8. Detection of GSH and GSSG
Caco-2 cells were seeded in a 60 cm2 culture dish (Corning, NY, USA). After treatment with different concentrations of SSM, cells were harvested and washed with PBS once. Then, cells were centrifuged, and cell pellets were used for detecting the intracellular amount of GSH and GSSG through a GSH/GSSG Assay Kit (Beyotime, Shanghai, China) according to the manufacturer’s protocol. The ratio of GSH/GSSG was calculated.
2.9. Small Interference RNA (siRNA) Transfection
Nrf2-specific siRNA and si-control were synthetized by RiboBio (Guangzhou, China). The target sequence of Nrf2 for this siRNA is GAGAAAGAATTGCCTGTAA (siB11731135640). Transfection was performed using Lipofectamine® 2000 on the basis of the manufacturer’s protocol.
2.10. Animal Experiments
C57BL/6 mice (6–8 weeks old, 18–22 g) were obtained from the Experimental Animal Center of Guangzhou University of Chinese Medicine and kept under specific pathogen-free animal facility. Mice were allowed ad libitum access to food (normal feed) and water and fed under controlled conditions at the temperature (), humidity (), and 12 h light-dark cycle. All animal experiments in this study were performed in strict accordance with the Guide for the Care and Use of Laboratory Animals of Sun Yat-sen University, in compliance with National Guidelines by the Animal Care and Use Committee. The protocol was approved by the Animal Ethical and Welfare Committee of Sun Yat-sen University (Approval No. IACUC-DD-15-1031).
Figure 2(a) describes the grouping design for animal experiments. After one-week adaption, mice were randomly divided into 5 groups (10 mice per group, 5 mice per cage), including (1) the control+physiological saline group, (2) 3% DSS+physiological saline group, (3) 3% DSS+50 mg/kg SSM group, (4) 3% DSS+100 mg/kg SSM group, and (5) 3% DSS+50 mg/kg 5-ASA group. Mice were given either normal drinking water (for the control model) or drinking water with 3% DSS (for the acute colitis model) from day 0 to day 6 and then received normal drinking water for another 3 days. Both SSM and 5-ASA were freshly prepared in physiological saline and then intragastrically administrated to the mice from day 0 to day 9. The daily intragastrical volume of drug solution for each mouse was adjusted for its daily body weight.
2.11. Macroscopic Assessment and Histological Examination
Mice were examined for diarrhea and bloody stool every day. Daily body weight and food intake were recorded. Mice were sacrificed at 24 h after the last administration, and blood samples were collected. The spleens were collected and weighed immediately. The colons were collected, and the length of the colon was measured immediately. One portion of the colon was fixed in 10% neutral buffered formalin and stained with H&E for histological examination, while the other parts were stored for biochemical analysis and western blot analysis. The activity of SOD and the amount of GSH, MDA, IL-6, IL-1β, and TNF-α in the colon were determined using commercial kits (Jiancheng Bioengineering Institute, Nanjing, China) based on the product’s specification.
2.12. Evaluation of Disease Activity Index (DAI)
DAI calculation was based on the scores of body weight loss, stool consistency, and rectal bleeding . The score of body weight loss was determined as follows: 0 = none, 1 = 1-5%, 2 = 5-10%, 3 = 10-20%, and 4 = >20%; the score of stool consistency was evaluated as follows: 0 = negative, 1 = +, 2 = ++, 3 = +++, and 4 = ++++; the score of rectal bleeding was determined as follows: 0 = normal, 1 = light loose stool, 2 = loose stool, 3 = light diarrhea, and 4 = diarrhea. The DAI was calculated through dividing the sum of these three scores by 3.
2.13. Statistical Analysis
SPSS 21 software (IBM, NY, USA) was used for the statistical analysis. The comparison between two groups was performed using Student’s -test, while comparisons among three or more groups were performed using one-way analysis of variance (ANOVA) with post hoc Tukey’s test to correct multiple comparisons. Figures were designed using Prism 8 (GraphPad, CA, USA). was statistically significant.
3.1. SSM Protected Caco-2 Cells from H2O2-Induced Cytotoxicity via GSH-Mediated ROS Scavenging
To confirm appropriate SSM concentrations used for this study, we first detected the cytotoxicity of SSM on Caco-2 cells. Figure 1(b) shows that Caco-2 cells failed to display significant growth inhibition even if they were treated with a high concentration of SSM (320 mM) for 24 h. Based on the past literatures related to SSM, 5, 10, 20, 40, and 80 mM were selected for this study. It is generally accepted that H2O2 can induce cytotoxicity that is similar with the oxidative stress injury in colitis . Therefore, H2O2 was employed in this part for evaluating the protective effect of SSM. As shown in Figure 1(c), exposure to single H2O2 for 24 h led to a concentration-dependent growth inhibition of Caco-2 cells. However, this cytotoxic effect was relieved by SSM (40 μM) pretreatment (4 or 8 h) (Figure 1(c)). Further results showed that monotreatment with H2O2 for 24 h led to a significant ROS increase in Caco-2 cells as evidenced by increased fluorescence intensity (green), while pretreatment with SSM (20, 40, and 80 μM) for 8 h significantly reduced intracellular ROS in a concentration-dependent manner (Figure 1(d)). Glutathione-S-transferase (GSH) is an essential antioxidant for scavenging ROS. Thus, we also tested the effect of SSM on GSH in Caco-2 cells. As shown in Figures 1(e) and 1(f), treatment with 40 and 80 μM SSM for 8 h significantly increased the intracellular amount of reduced GSH (GSH) to approximately 2.5- and 3-fold, respectively, whereas oxidized GSH (GSSG) was not influenced by SSM treatment. Moreover, pretreatment with BSO (a GSH synthesis inhibitor) markedly weakened the protective effect of SSM against H2O2-induced cell damage (Figure 1(g)). These results suggest that SSM may exert cytoprotective effect via GSH-mediated ROS scavenge.
3.2. SSM Promoted the Transcriptional Activation of Nrf2 in Caco-2 Cells
It is well known that GSH synthase is regulated by Nrf2/ARE signaling. To better clarify the mechanism underlying the protective effect of SSM, the transcriptional activity of Nrf2 under SSM treatment was detected by dual luciferase reporter assays. As shown in Figures 3(a) and 3(b), incubation with various concentrations of SSM (20, 40, and 80 μM) for 8 h significantly increased the ARE-driven luciferase activity in both Caco-2 and HEK293T cells. However, this effect was weakened after 16 and 24 h (Figures 3(a) and 3(b)). Consistently, qRT-PCR analysis showed that, after exposure to SSM (40 μM) for 8 h, mRNA expressions of several representative Nrf2-regulated genes, including HO-1, NQO1, GCLC (glutamate-cysteine ligase catalytic subunit), GCLM (glutamate-cysteine ligase modifier subunit), and GR (glutathione reductase), were increased by approximately 2-, 1.5-, 1.7-, 1.4-, and 2.2-fold, respectively, in Caco-2 cells (Figures 3(c)–3(g)). These results indicate that SSM can increase the transcriptional activity of Nrf2 and activate Nrf2/ARE signaling.
3.3. SSM Increased the Nuclear Translocation of Nrf2 and Induced Expressions of Cytoprotective Genes in Caco-2 Cells
Next, protein expressions of Nrf2 and downstream cytoprotective genes were also detected in SSM-treated Caco-2 cells (Figure 4(a)). Results showed that exposure to SSM (80 μM) for 8 h significantly upregulated the total protein expression of Nrf2 (Figure 4(b)). More importantly, treatment with 40 and 80 μM SSM for 2 h significantly increased the nuclear translocation of Nrf2 in Caco-2 cells, and this effect was further enhanced with the treating time extended to 8 h (Figure 4(c)). Consistently, protein expressions of NQO1, HO-1, GCLM, and GR were increased by 8 h SSM treatment (40 and 80 μM) (Figures 4(d)–4(g)). To investigate whether Nrf2 is essential for SSM-induced expressions of cytoprotective genes, si-control or Nrf2-specific siRNA was transfected into Caco-2 cells before treatment with SSM (40 μM). The result showed that Nrf2 knockdown significantly inhibited the inducible effect of SSM on NQO1, HO-1, GCLM, and GR (Figure 4(h)). Moreover, Nrf2 knockdown remarkably abolished the protective effect of SSM on H2O2-induced cytotoxicity (Figure 4(i)). These data indicate that Nrf2 activation is essential for the SSM-induced cytoprotective gene expression and cytoprotective effect.
3.4. SSM Activated Nrf2 Signaling through Promoting ERK and AKT Activation in Caco-2 Cells
It was reported that the activity of Nrf2 was regulated by Keap1 and several kinases, including ERK, AKT, P38, and PKC [8–11]. To further investigate the mechanism underlying SSM-induced Nrf2/ARE activation, the status of Keap1, ERK, AKT, P38, and PKC were detected using western blot analysis (Figure 5(a)). As shown in Figure 5(b), treatment with SSM (20, 40, and 80 μM) for 8 h elevated the phosphorylation level of ERK in a concentration-dependent manner. Similarly, the ratio of p-AKT/AKT was also significantly increased in the presence of SSM (20, 40, and 80 μM) (Figure 5(b)). However, P38 and PKCα were not significantly affected by SSM treatment (Figures 5(a) and 5(b)). Furthermore, the protein expression of Keap1 was significantly decreased by SSM (80 μM) after 8 h treatment (Figure 5(b)).
To investigate whether ERK and AKT are essential for SSM-induced Nrf2/ARE signaling activation, PD98059 and wortmannin [inhibitors for mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase pathway (PI3K), respectively] were used in this study. The inhibitory effects of these two inhibitors on ERK and AKT were confirmed using western blot analysis. Specifically, treatment with PD98059 (5 and 10 μM) and wortmannin (5 and 10 μM) for 2 h prior to SSM treatment significantly abolished SSM-induced phosphorylation of ERK and AKT, respectively (Figure 5(c)). Next, the protein expressions of Nrf2 and its targeted genes were further detected after inhibitor pretreatment. As shown in Figure 5(d), 10 μM PD98059 significantly abolished the inducible effect of SSM on HO-1, NQO1, GCLM, and GR. Similarly, 10 μM wortmannin significantly disrupted the effect of SSM on HO-1, NQO1, GCLM, and GR. More importantly, although total protein expression of Nrf2 was not influenced by inhibitor treatment (Figure 5(d)), the nuclear translocation of Nrf2 induced by SSM was significantly inhibited by PD98059 and wortmannin treatment as evidenced by the decreased nuclear protein expression of Nrf2 compared with the single SSM treatment group (Figure 5(e)). Consistently, pretreatment with PD98059 and wortmannin obviously disrupted the inhibitory effect of SSM on H2O2-induced ROS production (Figure 5(f)). Also, the protective effect of SSM against H2O2-induced cytotoxicity was significantly weakened by PD98059 and wortmannin as evidenced by Figures 5(g) and 5(h). These data suggest that SSM-induced Nrf2/ARE signaling activation and cytoprotective effect are dependent on ERK and AKT activation.
3.5. SSM Alleviated DSS-Induced Acute Colitis in Mice
DSS can induce murine acute colitis with pathologic features similar to human ulcerative colitis, and thus, it was employed in this study to evaluate the effect of SSM on colon injury , while 5-ASA was used as a positive control. The experiment design for animal study is shown in Figure 2(a). To assess the effect of SSM on DSS-induced colitis, the changes in food intake, body weight, disease activity index (DAI), and colorectal histopathology of mice were detected. The data showed that SSM (50 and 100 mg/kg) significantly improved food intake during the experiment (Figure 2(b)). Furthermore, DSS-treated mice showed obvious loss of body weight from day 2, while this was significantly improved by SSM treatment (50 and 100 mg/kg) (Figure 2(c)). Additionally, DSS-treated mice exhibited obvious diarrhea and rectal bleeding from day 5 and their DAI was increased time-dependently, while this situation was improved by SSM (50 and 100 mg/kg) or 5-ASA (50 mg/kg) treatment (Figure 2(d)). Compared with 5-ASA (50 mg/kg), SSM (50 mg/kg) showed a better symptom-improving effect when the DSS was removed (Figure 2(d)). More importantly, SSM (50 and 100 mg/kg) significantly inhibited DSS-induced shortening of the colon (50 mg/kg) (Figure 2(e)). Histopathological analysis showed that the colon tissue from DSS-treated mice displayed severe epithelial erosion and crypt distortion and abscess; this pathology was significantly prevented by cotreatment with SSM (50 and 100 mg/kg) (Figure 2(f)). These results suggest that SSM can alleviate DSS-induced acute colitis in mice.
3.6. SSM Reversed DSS-Induced Proinflammatory Cytokine Release and Antioxidation Inhibition
To further investigate the improving effect of SSM on DSS-induced colitis, the changes of proinflammatory cytokines, including interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor-α (TNF-α), were also detected in these mice. It was reported that the spleen weight is associated with the inflammation extent in colitis. Thus, the spleen weight was first compared in this part. As shown in Figure 2(g), the spleen weight was significantly increased in mice treated with DSS, while this was significantly alleviated by SSM (50 and 100 mg/kg). Consistently, DSS significantly increased the amount of IL-6, IL-1β, and TNF-α in colon tissues, while this was remarkably improved by SSM treatment (50 and 100 mg/kg) (Figures 2(h)–2(j)). Of note, SSM (100 mg/kg) almost reduced the release of these three proinflammatory cytokines to the normal level (Figures 2(h)–2(j)). Furthermore, some representative antioxidant factors, such as GSH, SOD, and MDA, were also detected in this part. As displayed in Figure 2(k), GSH was significantly decreased in colon tissues from DSS-treated mice compared with the control model. However, this was significantly reversed by SSM treatment (50 and 100 mg/kg) (Figure 2(k)). Meanwhile, after coadministration with SSM (100 mg/kg), the amounts of SOD and MDA were also significantly induced to the normal level (Figures 2(l) and 2(m)). These data thus suggest that SSM can inhibit the secretion of proinflammatory cytokines and enhance the antioxidant defenses against colitis.
3.7. SSM Reactivated Nrf2 Signaling via Activating ERK and AKT against DSS-Induced Colitis
To investigate whether activated Nrf2 signaling is involved in the protective effect of SSM in vivo, the protein expressions of Nrf2 and its targeted genes in the colon tissues of mice were measured in this study. As shown in Figure 6(a), DSS significantly decreased protein expressions of Nrf2, GCLC, GCLM, and GR. However, this effect was significantly reversed by SSM (50 and 100 mg/kg) (Figure 6(a)). Furthermore, the status of ERK, AKT, P38, PKC, and Keap1 was also detected in the colon tissues using western blot analysis. The results showed that DSS significantly inhibited the phosphorylation of ERK, AKT, and P38 and increased the expression of Keap1, while this inhibitory effect was significantly reversed by SSM (50 and 100 mg/kg) (Figure 6(b)). These data suggest that SSM can reactivate Nrf2-mediated protective defense through inducing ERK and AKT activation against DSS-induced colitis in mice.
UC is a chronic intestinal disorder localized in the mucosa and submucosa of the colon and has high incidence worldwide. Patients with UC have high risk of developing colitis-associated colon cancer . However, the mechanisms underlying the initiation or development of UC are still not fully understood, and many researchers struggled to find effective strategies for controlling symptoms better. In this study, we found SSM can enhance Nrf2-mediated protective defense against H2O2-induced oxidative stress in vitro and alleviate DSS-induced colitis in vivo. Our results demonstrate for the first time that SSM can activate Nrf2-mediated protective signaling against oxidative stress in colitis via inducing AKT and ERK activation. These data may provide a new insight into the antioxidative effect of SSM and propose it as a potential nutrition supplement for better managing symptoms of UC.
SSM is a major lignan of sesame seeds and reported to have anti-inflammatory and antioxidative activity . However, the mechanism underlying the protective effect of SSM is not fully understood. Considering the vital role of oxidative stress in colitis progress, we first tested the effect of SSM against H2O2-induced injury in Caco-2 cells and found that cotreatment with SSM significantly increased the viability of Caco-2 cells as compared to monotreatment with H2O2. Moreover, the intracellular overaccumulation of ROS induced by H2O2 was obviously relieved by SSM in a dose-dependent manner, which presents evidence for the antioxidative effect of SSM. Consistent with the increased scavenging of ROS, we found the GSH/GSSG ratio was elevated after SSM treatment. Thus, these data suggest that SSM can protect Caco-2 cells from H2O2-induced oxidative stress injury through GSH-mediated ROS scavenging.
Recent studies indicated that Nrf2 is a central transcriptional factor in a cellular antioxidative system. It makes us more interested in the role of Nrf2 in the SSM-induced antioxidative effect in this study. The results from ARE-luciferase reporter assay suggest that SSM can promote Nrf2 transactivation especially in the first 8 h, and this was further validated by immunoblotting experiments that showed the increased nuclear protein level of Nrf2 as well as the increased protein expression of several Nrf2-targeted cytoprotective genes. In contrast, Nrf2 knockdown significantly decreased their expressions induced by SSM, suggesting that the inducible effect of SSM on cellular antioxidative ability is dependent on Nrf2 activation.
DSS was proved to induce the disruption of epithelial barrier and colonic inflammation in the colon of mouse, which is pathologically similar with human UC . From in vivo study, we found that the amounts of IL-6, IL-1β, and TNF-α were significantly increased after single DSS administration, which is consistent with the change of spleen weight. These cytokines are released quickly at the inflammatory site and contribute to the acute inflammatory response . Thus, their occurrence in the colon manifested that the mouse model of UC was successfully established. Compared with the DSS monotreatment group, loss in body weight and reduction in food intake in the SSM cotreated groups were much lower during the recovery period (post DSS treatment), suggesting SSM significantly reversed DSS-induced inappetence. Moreover, mice treated with SSM also showed a much lower disease activity index (DAI) and significantly improved colon length compared with the DSS monotreatment group. These data along with histopathological evidence provide visible evidences for the improving effect of SSM on colitis and suggest that SSM-treated mice have better prognosis. Furthermore, the dysregulation of several oxidative stress indicators in the DSS monotreatment group suggests colon cells suffered from intense ROS attack during inflammatory reactions. This highlights the correlations between oxidative stress and inflammatory response in colitis. In contrast, cotreatment with SSM can effectively restore the expressions of GSH and SOD and reduce the secretion of IL-6, IL-1β, and TNF-α to the almost normal level of the murine colon. Interestingly, SSM showed a better protective effect as compared to 5-ASA in vivo. These evidences thus establish the potential role of SSM against DSS-induced UC.
On the other hand, we observed that DSS can decrease the protein expressions of Nrf2 and its targeted genes, while this situation can be reversed by the cotreatment with SSM. In fact, the reinduction of the Nrf2/ARE pathway by endogenous chemicals has been confirmed in many tissue cells to combat damaging inflammation through rectifying redox homeostasis. Also, chemicals with the ability of activating Nrf2 signaling usually display anti-inflammatory properties [31–35]. Therefore, the protective effect of SSM against murine colitis may be ascribed, at least partly, to its contributions to the reestablishment of the Nrf2-mediated cellular antioxidative system, suggesting the feasibility of treating UC via targeting excessive oxidative stress. Nonetheless, the involvement of the anti-inflammatory effect of SSM should not be neglected. The effect of SSM on inflammatory-associated signaling, such as the Toll-like receptor 4 signaling pathway, in colon cells needs further investigation .
Nrf2 is mainly regulated by Keap1 in the cytoplasm for polyubiquitination and subsequent degradation under basal homeostatic conditions. Mitogen-activated protein kinase cascade (MAPK), phosphoinositide 3-kinase pathway (PI3K), or PKC can regulate the translocation of Nrf2 to the nucleus via phosphorylation and promotes its nuclear accumulation [8–11]. In our study, we observed that the nuclear translocation of Nrf2 was promoted by SSM treatment. This led us to investigate whether the activation of ERK, AKT, p38, or PKC was involved in the process. Both in vitro and in vivo results showed that SSM can activate ERK and AKT, which is consistent with a study highlighting the angiogenesis-promoting effect of SSM . More importantly, the effect of SSM against H2O2-induced injury was abolished in vitro after AKT or ERK inhibition, suggesting the AKT or ERK activation is essential for SSM-induced protective effect. Further results showed that the inhibition of AKT or ERK weakened the promotive effect of SSM on Nrf2 nuclear accumulation and, as a result, Nrf2-regulated gene expressions. Research from other groups indicated that ERK or AKT activation is critical for Nrf2 nuclear accumulation and transcriptional response, and it was shown that Nrf2 can be phosphorylated at multiple sites by MAPKs (S215, S408, and S577) and glycogen synthase kinase 3β (GSK 3β, downstream protein kinase of AKT) (S342 and S347) [38–40]. ERK or AKT inhibition decreased the protein stability of Nrf2, promoted its degradation, and reduced its nuclear accumulation . These findings are consistent with our data showing that ERK and AKT activations are critical for SSM-induced Nrf2 transactivation. To our best knowledge, AKT and ERK are considered as integration points for multiple biochemical signals that play crucial roles in cell proliferation and differentiation . Thus, SSM-induced activation of AKT and ERK is in accord with the ability of SSM to promote cell proliferation, migration, and tube formation. However, the mechanism by which SSM activated ERK or AKT needs a further study .
Our study demonstrates that SSM can stimulate Nrf2-mediated protective defense against oxidative stress and inflammation in colitis via AKT and ERK activation. These data may provide a new insight into the medicinal value of SSM for UC treatment and propose it as a new candidate in order to gain more positive outcomes during IBD therapy.
The raw data supporting the findings of this study are available from the corresponding author on reasonable request.
Conflicts of Interest
There are no potential conflicts of interest in this study.
Xupeng Bai and Xiaoli Gou contributed equally to this work.
This work was supported by the National Natural Science Foundations of China (81573658 and 81102886) and the Guangdong Provincial Key Laboratory of Construction Foundation (2011A060901014 and 2017B030314030). We thank Dr. Zhiying Huang (School of Pharmaceutical Sciences, Sun Yat-sen University, China) for providing us with plasmids (pEF-Nrf2, pGL3-ARE, and pRL-TK).
Table 1: primers for quantitative real-time PCR. (Supplementary Materials)
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Dharma Pharmaceuticals is a locally owned company based in Bristol, Virginia and is committed to bringing high quality Cannabis Oil products to Virginia’s patients. With deep ties to southwest Virginia, we look forward to providing medical cannabis to Virginians seeking these new treatments.
Dharma Pharmaceuticals is thrilled to have been selected as one of five pharmaceutical processors in Virginia. The opportunity to serve our fellow patients with high quality Cannabis Oil is an honor. We are proud to be able to employ our fellow Virginians and help Bristol and Southwest Virginia begin to grow economically. Dharma Pharmaceuticals has had a two-fold mission from the beginning: delivering targeted medicinal cannabis products to Virginia’s patients in need and providing jobs for an economically distressed area.
THE EXECUTIVE TEAM
JACK L. PAGE
Founder & Chief Operating Officer
Jack Page was born and raised in Southwest Virginia. Since 2005, he has owned and operated local small businesses including a real estate title abstracting company and a real estate title insurance agency. Through the cultivation of strategic partnerships, these businesses have grown in both scope and size. Currently serving a 12-county area of southwest Virginia, he spearheads the efforts of a diverse team of trained professionals while creating and refining processes to position the companies for continued success. Jack has been a licensed title insurance underwriter since 2000 and is a Virginia Certified Title Examiner. He regularly conducts title examinations and writes title insurance policies on a wide range of properties from small residential homes to complex commercial properties. He is a member of the American Land Title Association, Virginia Land Title Association, and the National Association of Land Title Examiners and Abstractors.
Founder & Chief Executive Officer
Shanna Berry is a lifelong resident of Southwest Virginia. Shanna has been a licensed REALTOR with the Commonwealth of Virginia and State of Tennessee for over 17 years. She serves her extensive local client base through involvement with with every aspect of the marketing, sales and successful closings of multi-million dollar real estate portfolios. She is a member of the National Association of REALTORS, Virginia Association of REALTORS, Southwest Virginia Association of REALTORS, as well as the Northeast Tennessee Association of REALTORS. She has won numerous awards and accolades throughout her career. Shanna has an innate understanding of agriculture as she was raised in an agricultural business environment where her parents raised beef cattle, Burley tobacco, pumpkins, and Fraser fir Christmas trees. She resides in Abingdon, VA with her husband, a fifth-generation full time farmer, and three children on their 1,000 acre family beef cattle and dairy farm.
Founder & Chief Pharmacy Officer

domain: geography


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Dutch scientists have completed an analysis of their new smog-eating concrete. The special pavement can reduce nitrogen oxide air pollution by 45%, that translates as an average reduction of 19% percent over a day. The special concrete pavement is sprayed with titanium oxide (TiO2) able to convert air pollutants and convert them into less-dangerous chemicals, such as nitrates. The titanium dioxide pavement is more expensive than average cement; however, the cumulative benefits will be much higher than the ones received when using traditional pavement. Initial tests have demonstrated that the pavement could cost about 50% more than regular pavement although it only adds 10% more of what will cost the repaving of the road. The new pavement is expected to be tested during the next months in places such as Los Angeles, and other highly congested areas.
Photo Ik's World Trip

domain: chemistry


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San Juan del Norte or also called San Juan de Nicaragua, at the mouth of the river of the same name, near the Indio Maiz Reserve, is a small village where several indigenous communities live together. No roads but canals and small rivers. Its remoteness, its difficult access and its backwardness of development make it a particular and original destination. The old ghostly foundations of a canal project from the end of the 19th century can be seen there. You are in the Caribbean. Lovers of rare aquatic species or fishing fans, you are at the right port. Also the locals have some great stories to tell. The village cemeteries have some expatriates, English, Americans and even a consul of the German Empire. This is to tell you about the territorial and imperial disputes that took place here. There are still some border tensions with neighboring Costa Rica.
San Juan del Norte : isolated city at the mouth of the Rio San Juan in the Caribbean
San Juan del Norte is an isolated city lost in the jungle, its communication routes are essentially waterways, rivers and streams that serve as roads. Jungle and small lakes are scattered throughout the territory. Different ethnic communities lived there and its center is not far from the ruins of the old city. It is green and humid, we are at the gates of the lush Indio Maíz Biosphere Reserve and at the mouth of the river.
Upon the arrival of the Spaniards, the foundation of the city was quite rapid, they named the new colony San Juan del Norte, mainly because of its geographical position in what they called “el mar del norte”, the northern seas of the Caribbean. Looking at maps today, we can see the mistakes of the conquistadores and their nautical charts of the time.
San Juan del Norte, a strategic place, quickly becomes a commercial city, many goods transit between the colonial cities of the country, the Caribbean islands and Spain, of course.
In the 19th century, San Juan del Norte and other cities were attacked by the English, who often made alliances with the indigenous people present in the area to attempt a coup and thus impose the British crown. Jamaica is not very far, the governor of the time even managed an expedition and the conquest of the city which was then called Greytown. In honor of Sir Grey, the English governor. Thus the city became rich thanks to the port activity of the newly British city, there was no coincidence, the prosperity coincided then with the gold rush, these clouds of prospectors and adventurers on their way to California. During this period flourished British consulates and commercial warehouses in the area. Banks and casinos had also taken root in this prosperous new city. An alignment of wooden houses, in a very British architectural style, constituted the main road of the city. It is at this moment that the idea of an inter-oceanic canal germinated in the heads of the businessmen of San Juan del Norte. Technically that seemed feasible, the channel would be much easier at this precise place of the river, the flow of this last one would allow this prowess. Connecting the Atlantic and the Pacific!
Of course, the San Juan River was an excellent means of natural transportation, a low-risk estuary despite large sandbanks, and the north of the mouth was a real gateway. In the 19th century, a construction of gigantic dredgers was quickly carried out, at the same time the Panama Canal was being completed. The project in San Juan del Norte slowly sank into the bay.
Greytown had lost its strategic role and deteriorated. At the end of 1980, in the midst of the civil war, it was the scene of a fierce battle between the contras and Sandinistas. All that remained was the cemetery and a few damaged buildings.
The population gradually returned, the reconstruction of the city was in the projects, even a few kilometers away. A few families rebuilt San Juan del Norte, which is still a remote point with only 900 inhabitants.
How to get to San Juan del Norte, Nicaragua ?
The only way to reach San Juan del Norte is by sea :
- from San Carlos aboard a panga along the rio San Juan, departure twice a week
- from Costa Rica via the Caribbean Sea

domain: history


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There is a wealth of health-related benefits associated with cannabis. Healthcare professionals have been touting its health-related advantages for a long time. The most frequent ailments, it is known to become best for are the ones that cope with a number of sclerosis. A number of Sclerosis is an inflamation related ailment that has an effect on the central nervous system and that causes a myriad of indicators for instance lack of control, muscle spasms, serious ache and even just loss of sight. Most of these indicators are exactly like or are also associated with Crohn's Illness. Health-related marijuana shows in most cases to alleviate a number of the a lot more severe areas of the disease, leaving people that have the incurable ailment much more choices for cure.
Medicinal marijuana is usually suggested for those with many sclerosis, however many Sclerosis can be an incurable sickness. It truly is consumed supplement variety and is utilized to command specified indications of multiple sclerosis. It can also be generally recommended by doctors to help lessen the hurtful warning signs of Crohn's Condition. This has been known to lessen spasticity in patients with Crohn's disease, lessening a few of the requirement of on-going remedies and serving lower the necessity for surgeries and other interventions.
It is essential to message on the other hand, that healthcare cannabis is considered a Plan II ingredient, that means it is considered possessing a high prospects for neglect. People who use marijuana frequently will find their selves subjected to arrest and criminal prosecution within the National Managed Materials Take action. While not all health care cannabis users function afoul in the rules, people who do run the danger of giving up their convenience and losing their work. The federal government opinions the usage of marijuana as harmful and has submitted quite a few lawsuits to protect against persons it says it will have used marijuana while running a car. Just lately there had been a case in Canada wherein the us government stated which a Canadian resident who smoked cannabis was traveling intoxicated by the drug, despite the fact that he experienced a legitimate health-related medication to the medication. This example is currently simply being fought in the court.
The key manner in which cannabis helps reduce soreness is by presenting chemical contaminants known as CBD and THC. While they are all all natural, they should not be based in the exact same level in cannabis. For that reason, they work in a way that the body does not normally manufacture them. Such as, CBD can be obtained from the upholster with the head and also in the upholster of many of our eyeballs, although THC is just created in the liver as well as in the brain. The two of these harsh chemicals, with each other, are already proven to have an affect on our bodies plus they may help lessen the signs and symptoms connected with numerous sclerosis.
Other medical benefits of cannabis include things like the truth that it cuts down on the potential of establishing cancers and also lowering the possibility of creating lung and colorectal cancers. Some of the substances in marijuana, precisely THC and CBD, become contra --inflamation products. They have shown to have a very beneficial gain in treating osteoarthritis, including chronic suffering. Study in Israel found that both CBD and THC minimize joint pain in sufferers suffering from arthritis rheumatoid.
When utilised accurately, marijuana offers clients with lots of health improvements. The main, nevertheless, could possibly be the lowering of the signs affiliated with some forms of persistent agony. When applied as aimed, the health benefits of cannabis are incontestable. Professional medical cannabis people record a lot less frequency of head aches, a sick stomach together with other kinds of queasiness. Furthermore they review a lesser amount of ache for the duration of durations of physical activity and they sleep at night superior at nighttime.
The most used kind of medical cannabis, on the other hand, is most often marijuana. Right now there are around two dozens unique stresses of cannabis and many most women choose to use stresses which will not consist of THC. Ever since the major active component in marijuana is THC, these strains are viewed "risk-free" and therefore are the most popular. Although a lot of ladies report achievement with employing health-related weed, few are happy with the health advantages of cannabis. Several affected individuals report even, stomachaches and headaches nervousness and tension just after ingesting small quantities of cannabis. Some research workers and health professionals believe the chemical substance composition on the substance mysteriously has effects on neurological biochemistry and makes it a hardship on specified human brain receptors to respond.
Although some ladies never give some thought to tobacco use cannabis being a really serious make any difference, cigarette smoking cigarette smoking are just as hazardous. Regardless if a girl is not going to consider themselves to generally be enslaved by weed, she should not be working with it along with one other craving for example tobacco. Smoking marijuana is just not good for the body. Furthermore, by using cannabis may be very straightforward, in comparison with using smoking cigarettes. It is easier to purchase and quicker to commence smoking cigarettes a joint than it is to travel obtain a wrap up of smoking.
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domain: health


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One of the ladies at a crafting message board I read asked for birthday cards for a little boy who was going to be spending his 9th birthday in the hospital. I didn’t want to miss his birthday, so I made a quick card & sent it out with the next morning’s post.
For the card, I started with a cream card base out of my stash. I stamped the word background stamp from Stampers Anonymous Tim Holtz Collection (CMS106) Papillon stamp set with Tea Dye Distress Ink. I quickly added clear embossing powder to the stamped background because I didn’t want the words to blend into the layers I was going to add over top.
Once the embossing powder cooled, I placed my Mini Capricious 6×6 Template from The Crafter’s Workshop over the card & began rubbing Old Paper Distress Ink through the stencil. I moved the stencil around several times until I felt there were enough flourishes. Then I started adding Broken China Distress Ink with an ink applicator.
I liked the look so far, but it needed a bit more depth of color. A bit of Vintage Photo Distress Ink & a few pieces of tissue tape really brought out the layers & gave it a masculine feel.
Then all it needed was a bit of shimmer (Heirloom Gold Perfect Pearls Mist)…
Because the front of the card was a little busy, the sentiment was stamped inside the card. The Happy Birthday sentiment I used was from Close To My Heart (D1510) 4 My Friend stamp set, stamped with Jet Black Ranger Archival Ink. Of course, the card was signed & in the mailbox before I noticed that I hadn’t gotten a photo of the inside, so you’ll have to take my word for it.
- Non-stick Craft Sheet, Acrylic Blocks, Ink Applicator & Foam
- Distress Ink: Tea Dye, Old Paper, Vintage Photo, Broken China
- Stamper’s Anonymous Tim Holtz Collection: Papillon (CMS106)
- Clear Embossing Powder & Heat Tool
- The Crafter’s Workshop: Mini Capricious 6×6 Template
- Tissue Tape
- Perfect Pearls Mist: Heirloom Gold
- CTMH: (D1510) 4 My Friend
- Ranger Archival Ink: Jet Black

domain: artistic


First Flight: 7/7/2016
Last Flight: 7/7/2016
Takuya Onishi (大西 卓哉 Ōnishi Takuya, born 1975) is a Japanese astronaut selected for the Japan Aerospace Exploration Agency (JAXA) in 2009. He spent four months onboard the International Space Station in 2016.
Japan Aerospace Exploration Agency - JAXA
- Type: Government
- Abbreviation: JAXA
- Administration: Administrator: Hiroshi Yamakawa
- Founded: 2003
- Launchers: H-II
- Country: JPN
The Japan Aerospace Exploration Agency (JAXA) is Japan’s national aero-space agency. Through the merger of three previously independent organizations, JAXA was formed on 1 October 2003. JAXA is responsible for research, technology development and the launch of satellites into orbit, and is involved in many more advanced missions, such as asteroid exploration and possible manned exploration of the Moon. JAXA launch their Epsilon vehicle from the Uchinoura Space Center and their H-II vehicles from the Tanegashima Space Center.


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Union in the News for November 1, 2007
Union students take part in Habitat rehab
By Michael Goot - The Daily Gazette
With some sweat and muscle, a Barrett Street house will be completely remade as part of Habitat for Humanity’s latest project.
Union College donated the house at 1124 Barrett, which was among 13 purchased by faculty and staff under a plan to revitalize the neighborhood. After the school employee moved, the college assumed ownership of the house and decided to donate it to the organization that helps build and renovate affordable housing for low-income families.
President Stephen Ainlay said a group of Union students had gone to New Orleans to help with efforts to rebuild from Hurricane Katrina. They then began looking for another endeavor. The process was about a year and a half in the making.
“It all came together,” he said at a kickoff event on Wednesday.
Ainlay said he hopes that Union College can recruit additional students and staff so they can speed up the completion of the renovation. He hoped that the college would continue to be involved, even though it would not likely donate any more houses. He is excited about the potential for partnerships with the Habitat organization.
“Our hope is we will have a thriving [college] chapter in the years ahead,” he said.
College chapters of Habitat for Humanity are fairly common, with units including RPI, Skidmore College and The College of Saint Rose.
Chip Miller, a junior at Union College, said he was involved with Habitat for Humanity in high school and wanted to continue his association. However, there was nothing at Union College.
Miller serves as the philanthropy chairman for the Psi Epsilon fraternity and they got involved last winter with a project to empty out a warehouse that Habitat now uses. About a dozen students are involved in this effort.
“The best thing I enjoy is the fact that you see results day by day,” he said. “You really are doing a lot of work and you know that some family is going to be living in here. It’s going to be a great experience.”
Habitat for Humanity of Schenectady County Executive Director Jeffrey Clark said the house needs substantial work. It was originally built in 1910.
The college replaced the roof and had asbestos in the linoleum floor removed before turning it over to Habitat.
“Union College has just been terrific,” he said.
One section of the exterior walls will require extensive carpentry work. Volunteers have mostly gutted the inside of the twostory, 2,200-square-foot house but left the walls intact. They plan three bedrooms with a large unfinished area on the second floor. Also, they plan to put two bathrooms in the house — one on each floor — and plan to make them handicap-accessible.
The timetable is to have the house completed by the end of May. “With the help that Union College has pledged, we’re hoping that we can do better than that,” Clark said.
Clark said his organization’s board has been trying to step up its production and rehabilitation of houses. “We set a goal of doing 25 houses in five years.”
Chuck Steiner, president of the Chamber of Schenectady County, praised the partnership. “You’re talking about two wonderful institutions coming together to benefit us as a community,” he said. Volunteers such as Charlie Snyder of Mariaville will be working on the house each Wednesday and Saturday. Snyder retired from a state job in June and did not know anything about carpentry or construction.
“I love working with these people and doing something good for the community,” he said. “Now I can hammer a nail.” Working conditions can be difficult. “There’s a lot of dust and particles fl ying through the air. It gets in your eyes,” said Jeremy Burstyn, a Union College junior from Larchmont. However, there are some perks — like when he gets to knock down walls. “It’s fun to break stuff,” he said.

domain: news


Brad Garlinghouse, the CEO of Ripple Labs, stated that his company is prepared to escalate its legal dispute with the U.S. Securities Exchange Commission (SEC) to the Supreme Court if necessary. He expressed his determination to fight the SEC case during an interview, stating that Ripple is committed to seeing the legal process through. Garlinghouse emphasized the need for the United States to establish clear regulations that promote crypto innovation while protecting consumers. He cited other countries such as Japan, Singapore, Switzerland, the United Kingdom, and Australia as examples of jurisdictions with effective regulatory frameworks that have fostered institutional adoption of cryptocurrencies. Furthermore, Garlinghouse revealed that an opportunity for a settlement had been presented but was subsequently revoked, which he viewed as a sign of Ripple’s advantage in the case. He criticized the SEC’s approach and called for the regulatory agency to be part of the solution.
AI Sentiment: Neutral


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My Nonprofit Reviews
Review for Traveling Tutus Inc., Kissimmee, FL, USA
This is my first year with Traveling Tutus and I love it! I've done a fundraiser night and a collection drive so far and it's so much fun. I wanted to donate dance costumes I don't wear anymore, so when I found this I was so excited! I look forward to a great year with Traveling Tutus and many more to come.


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33" Phillips Collection Frozen Black Velvet Fabric Dining Chair with Matte Metal Frame
The Frozen Black Velvet Dining Chair is one of our most popular dining chairs. With its black velvet upholstery fabric and matte black metal frame, it is a shoe-in for both contemporary and mid-century modern interiors because we have tweaked the vintage profile to bring it seriously clean lines. Though it appears it could have been born in the swinging seventies, this is no disco-ball baby, as it was conceived by our design team in the 21st century. We offer a number of upholstery and frame finish options in this collection, and we have an arm chair in the mix. Each of these reflects the ethos that Phillips Collection personifies: modern organic.
Country of Origin: Philippines
Color: Matte Black
- Outdoor Use: No
- Care Instructions: Dust with a soft damp cloth. Do not use cleaning materials with strong chemicals. Not suitable for outdoor use.
Material: Velvet Fabric, Metal Frame

domain: design


About a week ago, AMD announced that Jim Killer would be returning to the company after previous stints at PA Semi, and later Apple after PA Semi was acquired back in 2008. Keller was an integral part of the AMD team that worked on the Athlon 64 and Opteron 64 projects.
In his new role at AMD, Keller wil be the corporate VP and chief architect of AMD’s microprocessor cores. And oddly enough, he’ll be reporting to Mark Papermaster who you might remember had a short lived stint at Apple as the company’s head of hardware engineering for both the iPhone and the iPod. Papermaster left Apple in 2010 amidst reports that he had lost the trust of Steve Jobs and had a tough time adjusting to Apple’s unique corporate culture.
In a press release on the matter, AMD stated:
“Jim is one of the most widely respected and sought-after innovators in the industry and a very strong addition to our engineering team,” said Papermaster.
“He has contributed to processing innovations that have delivered tremendous compute advances for millions of people all over the world, and we expect that his innovative spirit, low-power design expertise, creativity and drive for success will help us shape our future and fuel our growth.”
Keller was most recently a director in the platform architecture group at Apple focusing on mobile products, where he architected several generations of mobile processors, including the chip families found in millions of Apple iPads, iPhones, iPods and Apple TVs. Prior to Apple, Keller was vice president of design for P.A. Semi, a fabless semiconductor design firm specializing in low-power mobile processors that was acquired by Apple in 2008. While there, he led the team responsible for building a powerful networking SoC and its integrated PowerPC processor.


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For Tropical Lovers
Make it hot for just the right loved one with a blooming Tropical Bromeliad Garden, planted with an eye-catching trio of tropical beauties, then placed in a modern design cachepot in a complementary jungle green hue. We’ve found so many of our Flower Lovers are also devotees of these chic plants and here’s why.
Our grower is located deep down in South Florida, nestled between the Biscayne National Park and the Florida Everglades. The hot and humid summer climate along with the mild winters make ideal growing conditions for bromeliads. As they begin to grow they form a spiraling arrangement of leaves which is sometimes referred to as a “rosette.” This gives them not only a unique shape, but an interesting look compared to other ornamental plants.
The BSI (Bromeliad Society International) tells us, “Within the last hundred years, bromeliads have become more widely used as ornamental plants. Originally only found in royal botanical gardens or the private greenhouses of wealthy Europeans, their popularity has spread to the masses. Today bromeliads are more available to the enthusiast than ever before. New species are still being discovered and plant breeders are developing ever more stunning hybrids to choose from.”
Did you know that the most famous of all bromeliads is the pineapple?

domain: biology


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Chocolate Color & Text
Applies to duplicate prints
*Free Express shipping, coupons not applicable
^Free Standard shipping, coupons not applicable
Chocolate Brown Personalized Text Custom Ceramic Porcelain Round Ornament for Christmas, Holiday, Wedding, Anniversary, Pets, Dogs, Cats, Graduation, Baby, Engagement, Memorial
- Made of high quality white porcelain.
- Round: 3.25" diameter | Oval: 2.3" x 3.25" | Star: 3" diameter | Snow: 3" diameter | Heart: 3" x 3.24"
- Silver hanging ribbon is included.
- Photo printed directly on ornament
- For custom one side: Your design, photo or text will be printed in full color at the front, the back is white colored porcelain.
- For custom both sides: Your designs, photos or texts will be printed on both sides in full color and extends to edge.
- Presented in a handsome velvet drawstring bag, making it ready for gift-giving and providing protective storage year after year.
"I was very amazed at the quality of the magnets. I intend on using this website for future purposes. I was happy that I found this website...it was exactly what I had in mind. "
Jacx & Frankie Dela Cruz , Guam November 10, 2014


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Women's Basketball Extends Winning Streak To Three Games
Last second heroics give Spartans 74-72 win over Ohio State.
Feb. 8, 1998
COLUMBUS, Ohio - Freshman Becky Cummings sank two free throws with four seconds remaining to give Michigan State a thrilling 74-72 victory over Ohio State at St. John Arena. The victory improved MSU's overall record to 11-11, the first time the Spartans have been .500 since Dec. 30. The win also improved MSU's winning streak to a season-high three games and its Big Ten record to 5-7. The Buckeyes fell to 13-9 overall and 6-7 in the conference.
Senior Bella Engen's two free throws with 4:41 left in the game gave MSU its biggest lead of the game at 68-58. Ohio State's Larecha Jones and Marrita Porter sparked a comeback, leading the Buckeyes to a 13-2 run and a 71-70 lead with 2:27 left in the game.
MSU intentionally fouled Jamie Lewis with 17 seconds remaining and the Buckeye guard made one of two free throws to increase Ohio State's lead to 72-70. Engen then inbounded the ball to Jamie Wesley, who went coast-to-coast for a layup and the foul to knot the score at 72-72 with 11 seconds remaining.
Wesley missed the free throw, but sophomore Maxann Reese kept the ball alive, setting up Cummings' winning free throws.
Engen, Wesley and sophomore Kristen Rasmussen combined for 60 of MSU's 74 points with 20 points each.
Despite Ohio State's full-court pressure, MSU committed just 13 turnovers and shot 53 percent from the field.
"Their pressure kept us from executing our half court offense," Langeland said. "At the other end, they were going to Jones and Porter and we couldn't stop them."
Jones ended the contest with a game-high 29 points and 10 rebounds, while Porter had 22 points and seven rebounds.
With her 20 points, Wesley became just the ninth player in Spartan history to score 1,000 points. She ranks eighth all-time with 1,017 points.
MSU will host Purdue on Friday, Feb. 13 (7:30 p.m.), before facing league-leader Illinois on Sunday, Feb. 15 in Champaign, Ill., at 5 p.m., EST.


text: This museum will appeal to anyone interested in public transport. The collection of old trams and buses, plus transport memorabilia, is large. British visitors may be particularly interested in some of the buses and trams which were built in the UK or assembled in Portugal with British-supplied parts. The various parts of the museum are connected by an old tram, whose driver is invariably friendly and hospitable. Easily accessible from the city centre or Belem by tram 15.


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Bronchial anthracofibrosis and tuberculosis presenting as a middle lobe syndrome.
- Disease management
Bronchial anthracofibrosis, a clinical entity described less than a decade ago, is characterised by anthracotic pigmentation of the bronchial mucosa with multifocal bronchial lumen narrowing. The right middle lobe is predominantly involved and is frequently associated with tuberculosis. The condition is generally seen in non-smoking elderly ladies with a longstanding history of wood smoke exposure. A 65 year-old lady presented to us with a one-month history of dry cough. The chest radiograph revealed a middle lobe syndrome which was confirmed on computed tomography (CT) scanning. In addition, narrowing of the right middle lobe bronchus was seen. This raised the suspicion of a malignancy. Fibreoptic bronchoscopy revealed anthracotic pigmentation, and bronchial aspirate showed acid fast bacilli. Culture of the aspirate grew Mycobacterium tuberculosis. The patient responded to standard antituberculous treatment.


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medwireNews: Macular pigmentation correlates with visual acuity in healthy individuals and people with early age-related macular degeneration (AMD), study results indicate.
The findings raise the possibility of improving retinal function through the use of drugs that promote macular pigmentation, say the study authors writing in Acta Ophthalmologica.
Macular pigment is a yellow substance comprised of two dietary carotenoids, lutein and zeaxanthin, that builds up in the retina and is most dense at the center of the macula. The pigment selectively filters out short-wave light and also has antioxidant properties, leading researchers to hypothesize that it may protect against AMD.
In this study, María Puell (Complutense University, Madrid, Spain) and colleagues examined the relationship between macular pigment optical density (MPOD) and measures of visual function in 22 people with early AMD and 27 healthy age-matched control individuals.
MPOD was estimated at the fovea using the cathode ray tube-based Metropsis psychophysical vision test. The mean MPOD was 0.30 log units in healthy controls versus 0.27 log units in people with early AMD, a nonsignificant difference.
High-contrast and low-contrast visual acuity were also comparable between healthy patients and those with AMD, at 0.03 versus 0.06 logMAR for high-contrast and 0.24 versus 0.26 logMAR for low-contrast, respectively.
As none of these parameters differed between the groups, Puell's team undertook a regression analysis. This revealed statistically significant relationships between MPOD and high-contrast visual acuity, at an r-value of -0.47, and with low-contrast visual acuity, at an r-value of -0.46.
"Thus, as MPOD increased, visual acuity improved," explain Puell et al.
The researchers note that earlier studies have examined augmentation of MPOD through dietary supplementation with lutein and zeaxanthin and found that this intervention enhances visual function in people with AMD. The mechanisms whereby lutein supplementation affects retinal function have yet to be elucidated, however.
They conclude: "Further studies are required to address the relationship between macular pigment and visual function in AMD eyes with low baseline macular pigment levels.
"Specifically, we should try to determine the threshold MPOD level below which supplements known to increase macular pigment could be effective to improve vision."
medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013
By Joanna Lyford, Senior medwireNews Reporter

domain: medical


Well over three-quarters (81 per cent) of professionals who work in corporate governance or risk oversight say that a serious data breach caused by an unsecured IoT device is likely to occur in their business in the next two years.
The findings have been published in a joint report published by independent research company Ponemon Institute and the Shared Assessments Program, an industry body that focuses on third-party risk assurance.
The Internet of Things (IoT): A New Era of Third-Party Risk reveals that nearly all respondents – 97 percent – believe that an attack related to unsecured IoT devices could be “catastrophic” for their organisation.
A further 60 percent said they were concerned that the IoT ecosystem is particularly vulnerable to ransomware attacks.
What are they doing about it?
In terms of preventative measures, the survey found that only 28 percent currently include IoT-related risk as part of third-party due diligence, and 49 percent of respondents said they keep no inventory of IoT devices.
More than half (56 percent) don’t keep an inventory of IoT applications either, and a large majority (85 percent) say this is because of a lack of centralised control over these applications.
Other findings include:
• Only 46 per cent of respondents said their company has a policy in place to disable a risky or compromised IoT device.
• Just 29 per cent actively monitor the risks associated with IoT devices from third-parties. This is despite almost half of all organisations saying that they actively monitor IoT device risks within the workplace.
The report finds a major disconnect when it comes to third-party risk management practices, and reveals that many companies have fallen behind on assigning accountability too, with 38 percent of respondents admitting that nobody is responsible for reviewing third-party risk management policies and programmes.
There also seems to be a high-level of uncertainty about IoT device numbers in the workplace. Only nine percent of respondents said that they are fully aware of all of the devices connected to the internet within their businesses.
In other words, over 90 percent of organisations have no idea how many internet-connected devices exist in their offices.
More than one-quarter (26 percent) admit they are unsure if their organisation has been affected by a cyberattack involving an IoT device. More than one-third (35 percent) said they don’t know if it is even possible to detect a third-party data breach.
“While there’s an increasing awareness about third-party IoT risks, much more work needs to be done to ensure controls minimise the risks these devices pose,” said Charlie Miller, SVP of the Shared Assessments Program.
“With the increasing number of major data breaches, ransomware, and distributed denial of service attacks in the news daily, and senior executives losing their jobs as a result, it’s critical that organisations assign accountability and ownership of IoT-related oversight across their organisation, ensure that IoT security is taken seriously, and educate management at all levels,” he said.
Dr Larry Ponemon, chairman and founder of the Ponemon Institute, said that the bad news is that many organisations are continuing to struggle with the security risks posed by IoT. “They are therefore not prepared to deal with the catastrophic consequences of a breach,” he said.
“To more effectively address IoT risks and improve third-party risk management programmes, companies should take proactive steps to identify and replace inadequate IoT devices, assign accountability for monitoring the use and deployment of IoT devices, and collaborate with appropriate parties to find successful techniques to manage and mitigate third-party IoT device and application risks.”
Internet of Business says
Aside from the plethora of stories about connected cars and 5G testbeds, the dominant theme so far this year has been a woeful, perplexing, and sometimes alarming lack of preparedness for the security dimension of the IoT.
Some organisations have spent large sums of money securing traditional enterprise systems against hostile attack, malware and virus intrusion, or poor internal security processes.
However, while they have been doing so, the IoT has been expanding exponentially, bringing a large variety of different device types into the extended organisation.
Multiple reports have suggested that many such devices are being rushed to market to capitalise on the growing wave of IoT interest, while others may be devices that have never been connected to the internet before, and therefore may lack up-to-date security protocols.
Factor in 5G too – as our in-depth report reveals – and any organisations that believe they have little risk exposure from the IoT may find that snowballing into a huge problem over time. Tackling those issues now is essential.
Just some of our 2018 security reports so far:-
IoTBuild is coming to San Francisco, CA on March 27 & 28, 2018 – Sign up to learn all you need to know about building an IoT ecosystem.


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text:
This is a continuation of a Birmingham News story that began HERE
Inmates who have cell phones are violating prison rules, but because there is no law making it a crime for them to have the phones, their only punishment is a denial of prison privileges.
If finding the phones and preventing them from coming into a prison is hard enough, SIM cards make it that much harder, prison officials say. A phone won't work without a SIM -- subscriber identity module -- card. Several inmates who have memory chips can use a single phone simply by switching out the SIM card.
"We routinely train our staff on the detection of all contraband, including SIM cards, to ensure that inmates are not violating policy or engaging in unauthorized activities," Ponce said.
Smuggling them in
Inmates continue to find creative ways to get cell phones. Someone recently placed 10 phones in a mailbox at the home of an Alabama warden, DeLoach said. The plan was for an inmate garbage crew to come by and retrieve the package.
"Luckily the warden's children saw this strange car come up and put something in the mailbox and they alerted their dad," he said.
In prison, phones can cost as much as $300, especially for the more expensive models, such as a BlackBerry.
"It used to be we'd get the little cheap TracFones that you could get from Wal-Mart. Now we're getting BlackBerrys," said Capt. Richard Naile, a shift supervisor at Elmore Correctional Facility, one of two major prisons next to Draper. "Until they make it a crime for them to possess a cell phone, we're never going to stop it."
Last summer, Naile said, members of the Correctional Emergency Response Team searched two of Elmore's three dorms, which are home to about 800 inmates. They found 80 cell phones. Thirteen more later were found in a pile of inmate clothing near the prison's back gate.
"So you're talking about some big money," said Vernon Barnett, the Alabama prison system's chief deputy commissioner. "It's not as if it were drugs where if you get caught bringing drugs into the prison, you're going to do some hard time. Cell phones are not illegal on the outside...so they're not risking quite as much."
Earlier this month, a shakedown at Donaldson Correctional Facility in west Jefferson County yielded 18 cell phones and three Bluetooth headsets. Also turned up were items that indicated traditional contraband is far from a thing of the past: 31 knives, a digital drug scale and packages of marijuana, cocaine and pills.
Many of the phones found in Alabama prisons -- DeLoach figures about half -- are brought in by staff members looking to make extra cash, officials said.
"We are prosecuting, of course," he said, "but district attorneys, with their caseloads being what they are, they're not placing a high priority on prosecuting a former correctional officer for smuggling cell phones."
Inmates who are caught with a phone can be punished through a loss of privileges, such as fewer visits to the prison store, or be given extra duties, Naile said.
Fighting the problem
Prisons across the country are trying to find ways to combat the problem, from high-tech sensors to dogs trained to sniff out cell phone parts. Mississippi is using metal detectors in Unit 32, its 1,000-bed maximum-security facility at the state penitentiary at Parchman, and spokesman Kent Crocker said the devices have helped reduce the number of illicit cell phone. Virginia uses dogs.
A prison in Texas recently experimented with jamming cell phone signals, but a demonstration of the jamming device was canceled after the state attorney told prison officials that jammers are illegal under federal law.
"Cell phones in prisons, as Yogi Berra would say, are ubiquitous and everywhere," said Terry Bittner, director of security products of ITT Corp., a Maryland-based company that works with prisons to keep cell phones out of inmates' hands.
Bittner said ITT has developed a system by which sensors are installed near cellblocks. If an inmate makes a call, receives a text message or simply turns on his phone, an alert is sent to a central server. The server locates the source of the signal. A map of the facility flashes on a computer screen at a guard station, pinpointing the phone's location.
"It allows the staff to be much more efficient," Bittner said. "When doing a shakedown, they can target their search instead of looking in every cell."
Bittner said the technology has been used in several federal prisons since 2005. State prisons in Virginia, Pennsylvania and South Carolina also use it.
Alabama prison officials said that, for now, the system will depend on random shakedowns. "We've looked at various technology, but we haven't found anything yet that we'd be willing to open the pocketbook for," system spokesman Brian Corbett said.
In any event, the system would be hard pressed to find the dollars to buy the tools to combat cell phones. Corrections Commissioner Richard Allen said earlier this year that Alabama is 49th in the country in spending for prisoners, and Corbett said a single dog trained to detect mobile phones can cost as much as $25,000.
At Elmore, Warden Willie Thomas said part of the phone problem lies in the ratio of inmates to officers. During a typical shift at the prison, there are about 100 or more prisoners for each officer. The presence of more officers would reduce the cell phone flow, he said.
"It's simple arithmetic."


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Bitcoin and Ether rose in a mixed morning for the top 10 unstable cryptocurrencies by market capitalization. Solana posted the biggest gains while Polygon’s Matic led losses Tuesday morning in Asia.
See related article: Bitcoin Surpasses Visa’s Market Cap to Become World’s 11th Largest Asset
- Bitcoin is up 2.1% in the past 24 hours to trade at US$24,833 as of 8 a.m. in Hong Kong, taking its gains to 13.9% in the past calendar week, according to CoinMarketCap. Ethereum gained 1.3% to US$1,703, up 13% in the past seven days.
- Solana rose 5.5% in the past 24 hours and 26.1% for the week to US$26.22 after Helium Network, a blockchain project dedicated to improving connectivity in the internet of thingsannounced on Saturday its intention to merge with Solana at the end of March. Helium’s HNT token, the 95th largest cryptocurrency by market cap, rose 10% to US$3.19, a weekly gain of 31.3%.
- Polygon’s Matic fell 0.4% to US$1.47, but was still trading up 24.4% US for the week.
- XRP rose 3.1% to $0.39, taking its weekly gains to 7.4%, after Ripple Labs Inc., the developer of the XRP-powered payment network Ripple, tweeted it is recruiting new engineering positions on Monday. The company now has 75 open positions in total, according to its website.
- The total crypto market cap rose 1.2% to US$1.13 trillion as of 8am Hong Kong. Total trading volume in the past 24 hours increased by 16.4% to $64.8 billion.
- Many major U.S. retailers are expected to release holiday season earnings this week, starting with Walmart Inc. and Home Depot Inc. on Tuesday. Earnings reports are set to come amid growing fears of a U.S. recession as the Federal Reserve raised interest rates from near zero to 4.5% to 4.75% to calm the economy. ‘inflation.
- The latest consumer price index data showed inflation rose to 6.4% in January from a year ago, from 6.5% in December and 7.1% in November . Analysts at CME Group predict about an 80% chance that the Fed will raise rates another 25 basis points next month.
- U.S. stocks will resume trading on Tuesday after closing Monday for Presidents Day.
See related article: Hong Kong Begins Public Consultation on Crypto Licensing Regime


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getting rid of moles use of natural repellents: This is how to get rid of moles naturally. Planting garlic and chocolate lilies in your garden is a very effective natural way to control them as moles dislike these plants. They will go and find a place that is devoid of such plants when you do so.
Aspirin is the remedy for fungal plant problems, Black spot, powdery mildew, and rust are a terrible trio of fungi, which can attack and destroy your plants. Scientists have found that two uncoated aspirin tablets (325 milligrams each) dissolved in 1 quart of water and used as a foliar spray can thwart these diseases.


text: Sign in to favourite Sign in to add to album Geographical notes close Places are defined in terms of modern geography. Copyright Information close The author of this artwork died more than 70 years ago. According to U.S. Copyright Law, copyright expires 70 years after the author's death. In other countries, legislation may differ. More… WikiArt.org allows unlimited copying, distributing and displaying of the images of public domain artworks solely. We use here Copyright term based on authors' deaths according to U.S. Copyright Law, that is 70 years. In other countries, the duration of copyright term may differ. Please check here copyright length according to your country's legislation before you consider reproducing images borrowed from Wikipaintings.org Artworks protected by copyright are supposed to be used only for contemplation. Images of that type of artworks are prohibited for copying, printing, or any kind of reproducing and communicating to public since these activities may be considered copyright infringement. Public domain ← → Roses Henri Fantin-Latour Date: 1871 Style: Realism Genre: flower painting Media: oil, canvas Dimensions: 22.5 x 21.6 cm Location: Private Collection File Source: www.the-athenaeum.org Order an oil painting reproduction Ad Image dimension 723x600px, View all sizes Henri Fantin-Latour Famous works Flowers Camelias and Tulips Henri Fantin-Latour · 1862 Homage to Delacroix Henri Fantin-Latour · 1864 A Studio in the Batignolles (Homage to Manet) Henri Fantin-Latour · 1870 The Corner of the Table Henri Fantin-Latour · 1872 The Dubourg Family Henri Fantin-Latour · 1878 Flowers Large Bouquet with Three Peonies Henri Fantin-Latour · 1879 Undine Henri Fantin-Latour · 1896 Bathers by the Sea Henri Fantin-Latour · 1898 View all 289 artworks Related Artworks Caricature of Matthew Arnold James Tissot The Barricade (Civil War) Edouard Manet Caricature of John George Dodson M.P. James Tissot Arrangement in Grey and Black No.1, Portrait of the Artist's Mother James McNeill Whistler Caricature of William Henry Gregory James Tissot Caricature of John Pender James Tissot Caricature of George Cavendish Bentinck James Tissot The Country School Winslow Homer The Dreamer (Summer Evening) James Tissot Caricature of Henry Cole James Tissot Dilke, Charles Wentworth James Tissot Caricature of Alexander Baillie Cochrane M.P. James Tissot The Port of Bordeaux Edouard Manet Collecting the Nets Konstantinos Volanakis The Farewell James Tissot The Port of Bordeaux Edouard Manet Caricature of Henry William Eaton M.P. James Tissot Caricature of Anthony John Mundella James Tissot On the Thames, a Heron James Tissot Young Woman in Oriental Garb Edouard Manet 1 Load more Advertisement.


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