Progress 02/01/14 to 01/31/19
Outputs
Target Audience:I have delivered science-based knowledge (e.g., design and implementation of animal intervention studies; interpretation and demonstration of animal model experiments; preparation and administration of special animal intervention diets; preparation and administration of DSS for colitis induction; measurements of clinical colitis; animal anesthesia and blood and tissue collection procedures; histopathological procedures; histopathological evaluations; blood and tissue processing and extraction; HPLC analysis procedures; molecular pathways of inflammation; measurements of molecular markers of inflammation; immunohistochemical staining procedures; microscopic quantification of immunohistochemical staining results; data analysis; data interpretation; and data presentation) to other researchers, post-docs, visiting scientists, and graduate students through laboratory demonstrations and instructions, laboratory meeting discussions, national and international scientific conference discussions, and experiential learning opportunities. I have also applied the methods developed from this project to other studies, which contributed to their successful completion. Other researchers, post-docs, visiting scientists, and graduate students have also used the methods developed from this project for their studies. Additionally, I have submitted and presented the abstracts and posters and discussed the study findings from this project at large national and international scientific conferences that were attended by broad scientific audiences (Experimental Biology meeting, American Association for Cancer Research conference, and Advances in Inflammatory Bowel Diseases conference). The abstracts for Experimental Biology and American Association for Cancer Research meetings were published in the program and proceedings and the journal, which reached the general public. Moreover, I have submitted and presented the study findings from this project to the USDA/NIFA AFRI Function and Efficacy of Nutrients and Improving Food Quality Program Directors' Meetings every year throughout the grant period. Conference and meeting presentations and publications related to this project are listed below. • Liu C, Bronson RT, Wang XD. Dietary lutein and kale decrease DSS-induced colonic inflammation and associated preneoplastic and neoplastic lesions. 2018 USDA/NIFA NRI/AFRI Function and Efficacy of Nutrients (A1341) and Improving Food Quality (A1361) Project Director Meeting. Boston, MA, June 8, 2018. • Liu C, Bronson RT, Wang XD. Dietary lutein and kale intakes modulate colonic inflammation in the DSS mouse model of colitis. 2017 USDA-NIFA Joint Project Director's Meeting - Improving Food Quality and Function and Efficacy of Nutrients. Las Vegas, Nevada, June 24, 2017. • Liu C, Bronson RT, Wang XD. Biological effects of lutein and kale on the prevention of colonic inflammation and carcinogenesis. Program and Proceedings of the American Association for Cancer Research Special Conference on Colorectal Cancer: From Initiation to Outcomes. Poster Session A. A31. Page 62. Tampa, FL, September 17-20, 2016. • Liu C, Bronson RT, Wang XD. Biological effects of kale and lutein on the prevention of colonic inflammation and associated preneoplastic and neoplastic lesions. 2016 USDA/NIFA AFRI Function and Efficacy of Nutrients, Improved Processing Technologies, and Improving Food Quality Program Directors' Meeting. San Diego, CA, April 6, 2016. • Liu C, Bronson RT, Wang XD. Biologic Effects of Kale and Lutein on the Prevention of Colonic Inflammation. 2015 USDA/NIFA - AFRI/NRI Function and Efficacy of Nutrients/Bioactive Components for Optimal Health, and Improving Food Quality Program Director's Meeting. Chicago, IL, July 10, 2015. • Liu C, Bronson RT, Wang XD. Lutein Supplementation on the Prevention of Colonic Inflammation and Neoplasia in Mice. Experimental Biology 2015. Boston, MA, March 28 - April 1, 2015. • Liu C, Bronson RT, Wang XD. Effects of Lutein Supplementation on the Prevention of Colonic Inflammation and Neoplasia in Mice. FASEB J April 2015 29:767.3 Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?This study has also included a component of the training of visiting scientists, post-docs, graduate students, and laboratory technician. Through participating in research activities, the trainees have gained hands-on experience in designing and implementing animal intervention studies and in conducting laboratory and histopathological experiment procedures, histopathological evaluations, immunohistochemical staining procedures, and microscopic quantification of immunohistochemical staining results. I have delivered science-based knowledge (e.g., design and implementation of animal intervention studies; interpretation and demonstration of animal model experiments; preparation and administration of special animal intervention diets; preparation and administration of DSS for colitis induction; measurements of clinical colitis; animal anesthesia and blood and tissue collection procedures; histopathological procedures; histopathological evaluations; blood and tissue processing and extraction; HPLC analysis procedures; molecular pathways of inflammation; measurements of molecular markers of inflammation; immunohistochemical staining procedures; microscopic quantification of immunohistochemical staining results; data analysis; data interpretation; and data presentation) to post-docs, visiting scientists, and graduate students through laboratory demonstrations and instructions, laboratory meeting discussions, and experiential learning opportunities. How have the results been disseminated to communities of interest?Through the presentations of the study results at national and international scientific conferences attended by broad scientific audiences and through the publication in the journal that reaches the general public. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
We have completed all study aims proposed. 1. We conducted the kale and lutein intervention studies using the dextran sulfate sodium (DSS)-induced mouse colitis model, including the preparation and animal feeding with diets containing 4 doses of lutein and 4 different amounts of kale power (equivalent to 4 lutein doses), the administration of DSS, weekly clinical colitis evaluations (loose stool, hemoccult testing), weekly body weight measurements, mortality monitoring, and blood and tissue collection of the 260 study mice. As planned, the DSS administration and the kale and lutein interventions for the 260 study mice were conducted in two batches (130 female mice as batch one and 130 male mice as batch two) because of large sample size (n=260). Each batch took about 6 months for a total of approximately 12 months. Two hundred sixty four 8-week old Swiss-Webster (CFW) mice were assigned to one of ten groups (n = 26 to 27 in each group [13 males and 13 to 14 females]) for 21 weeks as follows: 1) 0.0005% of lutein plus DSS; 2) 0.001% of lutein plus DSS; 3) 0.002% of lutein plus DSS; 4) 0.005% of lutein plus DSS; 5) kale equivalent to 0.0005% of lutein plus DSS; 6) kale equivalent to 0.001% of lutein plus DSS; 7) kale equivalent to 0.002% of lutein plus DSS; 8) kale equivalent to 0.005% of lutein plus DSS; 9) DSS only; and 10) control with no treatment. During the 21-week experimental period, mouse body weights, loose stool, and hemoccult testing were recorded weekly. At week 7, the mice in groups 1-9 were given DSS for 4 cycles (1 cycle = 1 week 3% of DSS in drinking water followed by 2-week water) to induce colitis and colorectal neoplasia. There were no differences in body weights at the end of the study among all intervention groups. The study results show that dietary lutein and kale intakes, particularly two higher doses (0.002% and 0.005%), greatly decreased the DSS-induced hemoccult and loose stools (clinical signs of colitis) in both male and female mice. Moreover, dietary lutein and kale intakes, particularly two higher doses, reduced the DSS-caused mortality in mice. 2. We performed HPLC assays of plasma and colonic tissue levels of lutein, lutein isomers, and lutein metabolites of the 260 study mice and conducted data analyses. The study results show that dietary lutein and kale supplementation dose-dependently increased plasma and colon lutein levels in both male and female mice. 3. We conducted colonic tissue histopathology fixation, processing, embedding, sectioning, and H & E staining, and histopathological evaluationsof the 260 study mice and conducted data analyses. The study results show that dietary lutein and kale intakes, especially two higher doses (0.002% and 0.005%), decreased the DSS-induced colorectal inflammation, ulceration, hyperplasia, dysplasia, adenoma, and adenocarcinoma in both male and female mice. 4. We performed immunohistochemical staining and microscopic quantification of immunohistochemical staining results of a variety of molecular markers of colonic inflammation of the 260 study mice and data analyses. These immunohistochemical staining results of molecular markers helped illustrate the underlying molecular mechanisms of biologic effects of lutein and kale vegetable on the prevention of colonic inflammation. 4a. We measured colonic tissue protein levels of (a) upstream proteins of NF-κB and AP-1 (phospho-IKKα/β [ser 176/180], phospho-JNK, phospho-p38 MAPK and phospho-ERK1/2); (b) activation of NF-κB (p65) and AP-1 (c-Jun and c-Fos); (c) NF-κB and AP-1 targets (pro-inflammatory markers [TNFα, IL-6, and cyclooxygenase-2 (COX-2)], cell proliferation markers [cyclin D1, ki67, and proliferating cellular nuclear antigen (PCNA)], and apoptosis [cleaved caspase-3]); and (d) anti-inflammatory marker of IL-10 (which can block NF-κB activity) of the 260 study mice and conducted data analyses. The study results show that dietary lutein and kale intakes decreasedthe DSS-induced phospho-IKKα/β (ser 176/180), phospho-JNK, phospho-p38 MAPK, phospho-ERK1/2, NF-κB (p65) nuclear accumulation, and AP-1 (c-Jun and c-Fos), cell proliferation markers of cyclin D1, ki67, and PCNA, and pro-inflammatory markers of TNFα, IL-6, and COX-2, as well as cleaved caspase-3 (an apoptosis marker) in both male and female mice. We also found that dietary lutein and kale intakes upregulated IL-10 (an anti-inflammatory marker). 4b. We measured colonic tissue nuclear accumulation of Nrf2 and protein levels of Nrf2-regulated phase II detoxification or antioxidant enzymes (HO-1 and NQO1) of the 260 study mice and conducted data analyses. The study results show that dietary lutein and kale intakes upregulated Nrf2 nuclear accumulation and protein levels of Nrf2-regulated phase II detoxification or antioxidant enzymes (HO-1 and NQO1) in both male and female mice. 4c. We measured colonic tissue protein levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a sensitive, stable and integral marker of oxidative damage in cellular DNA of the 260 study mice and conducted data analyses. The study results show that dietary lutein and kale intakes decreased the DSS-induced 8-OHdG. In conclusion, the findings from this study indicate that kale and lutein prevent colonic inflammation and associated colorectal neoplasia through suppressing NF-κB and AP-1 mediated responses, enhancing Nrf2-mediated phase II detoxification or antioxidant enzymes, and reducing oxidative stress and damage, and that kale and lutein are promising chemoprevention agents against colonic inflammation and carcinogenesis. Findings from this intervention study of kale and lutein in four doses that are relevant to human intakes in a relevant mouse model provide important evidence of the role of kale and lutein in preventing colonic inflammation and associated neoplasia, help elucidate the underlying molecular mechanisms, and provide a basis for conducting human intervention trials. The demonstration of the benefit of kale and lutein in the prevention of colonic inflammation and colitis- associated colorectal neoplasia from this study also provides strong support for public health recommendations on increasing consumption of kale and other lutein-rich dark green leafy vegetables. Biomarkers measured in this study also have broad application in the study of other nutrients and can serve as intermediate endpoints in future human intervention trials.
Publications
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2018
Citation:
Liu C, Bronson RT, Wang XD. Dietary lutein and kale decrease DSS-induced colonic inflammation and associated preneoplastic and neoplastic lesions. FY 2018 USDA/NIFA NRI/AFRI Function and Efficacy of Nutrients (A1341), and Improving Food Quality (A1361) Project Director Meeting. Boston, MA, June 8, 2018.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Liu C, Bronson RT, Wang XD. Dietary lutein and kale intakes modulate colonic inflammation in the DSS mouse model of colitis. 2017 USDA-NIFA Joint Project Director's Meeting - Improving Food Quality and Function and Efficacy of Nutrients. Las Vegas, Nevada, June 24, 2017.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2016
Citation:
Liu C, Bronson RT, Wang XD. Biological effects of lutein and kale on the prevention of colonic inflammation and carcinogenesis. Program and Proceedings of the American Association for Cancer Research Special Conference on Colorectal Cancer: From Initiation to Outcomes. Poster Session A. A31. Page 62. Tampa, FL, September 17 - 20, 2016.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2016
Citation:
Liu C, Bronson RT, Wang XD. Biological effects of kale and lutein on the prevention of colonic inflammation and associated preneoplastic and neoplastic lesions. 2016 USDA/NIFA AFRI Function and Efficacy of Nutrients, Improved Processing Technologies, and Improving Food Quality Program Directors' Meeting. San Diego, CA, April 6, 2016.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2015
Citation:
Liu C, Bronson RT, Wang XD. Biologic Effects of Kale and Lutein on the Prevention of Colonic Inflammation. 2015 USDA/NIFA AFRI/NRI Function and Efficacy of Nutrients/Bioactive Components for Optimal Health, and Improving Food Quality Program Director's Meeting. Chicago, IL, July 10, 2015.
- Type:
Journal Articles
Status:
Published
Year Published:
2015
Citation:
Liu C, Bronson RT, Wang XD. Effects of Lutein Supplementation on the Prevention of Colonic Inflammation and Neoplasia in Mice. FASEB J April 2015 29:767.3
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2015
Citation:
Liu C, Bronson RT, Wang XD. Lutein Supplementation on the Prevention of Colonic Inflammation and Neoplasia in Mice. Experimental Biology 2015. Boston, MA, March 28 - April 1, 2015.
|
Progress 02/01/17 to 01/31/18
Outputs
Target Audience:I have delivered science-based knowledge (e.g., design and implementation of animal intervention studies; interpretation and demonstration of animal model experiments; preparation and administration of special animal intervention diets; preparation and administration of DSS for colitis induction; measurements of clinical colitis; animal anesthesia and blood and tissue collection procedures; histopathological procedures; histopathological evaluations; blood and tissue processing and extraction; HPLC analysis procedures; immunohistochemical staining procedures; microscopic quantification of immunohistochemical staining results; data analysis; and data presentation) to post-docs, visiting scientists, and graduate students through laboratory demonstrations and instructions, laboratory meeting discussions, and experiential learning opportunities. In addition, I have submitted and presented the abstract and poster of the components of data from this grant to a large national/international scientific conference that was attended by broad scientific audiences (2016 American Association for Cancer Research [AACR] Special Conference on Colorectal Cancer: From Initiation to Outcomes). The abstract for this AACR conference was published in the program and proceedings, which can reach the general public. Moreover, I have submitted the findings on the clinical evaluations of colonic inflammation and the findings from histopathological evaluations to the 2017 USDA-NIFA Joint Project Director's Meeting - Improving Food Quality and Function and Efficacy of Nutrients that was held in Las Vegas, Nevada on June 24, 2017. Conference presentations and publications related to this project in this reporting period are listed below. Liu C, Bronson RT, Wang XD. Dietary lutein and kale intakes modulate colonic inflammation in the DSS mouse model of colitis. 2017 USDA-NIFA Joint Project Director's Meeting - Improving Food Quality and Function and Efficacy of Nutrients. Las Vegas, Nevada, June 24, 2017. Liu C, Bronson RT, Wang XD. Biological effects of lutein and kale on the prevention of colonic inflammation and carcinogenesis. Program and Proceedings of the American Association for Cancer Research Special Conference on Colorectal Cancer: From Initiation to Outcomes. Poster Session A. A31. Page 62. Tampa, FL, September 17 - 20, 2016. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?This study also includes a component of the training of visiting scientists, post-docs, graduate students, and laboratory technician. Through participating in research activities, the trainees have gained hands-on experience in designing and implementing animal intervention studies and in conducting laboratory and histopathological experiment procedures, histopathological evaluations, immunohistochemical staining procedures, and microscopic quantification of immunohistochemical staining results. I have delivered science-based knowledge (e.g., design and implementation of animal intervention studies; interpretation and demonstration of animal model experiments; preparation and administration of special animal intervention diets; preparation and administration of DSS for colitis induction; measurements of clinical colitis; animal anesthesia and blood and tissue collection procedures; histopathological procedures; histopathological evaluations; blood and tissue processing and extraction; HPLC analysis procedures; immunohistochemical staining procedures; microscopic quantification of immunohistochemical staining results; data analysis; and data presentation) to post-docs, visiting scientists, and graduate students through laboratory demonstrations and instructions, laboratory meeting discussions, and experiential learning opportunities. How have the results been disseminated to communities of interest?Through the presentation of the results at national and international scientific conferences attended by broad scientific audiences and through the publication in the journal that reaches the general public. What do you plan to do during the next reporting period to accomplish the goals?We will continue our efforts for completing the remaining immunohistochemical staining and microscopic evaluations and data analyses, as well as manuscripts preparation during the next reporting period. I will also continue to attend conferences to present and disseminate study results from this project.
Impacts
What was accomplished under these goals?
Ulcerative colitis, a chronic inflammatory disease, increases risk of colorectal cancer. Lutein, a bioactive food component, is inversely associated with systemic inflammatory markers and colorectal cancer risk in observational studies. The major sources of lutein in the American diet are green leafy vegetables such as kale. Kale is among the most commonly grown vegetables worldwide. Besides lutein, kale contains abundant amounts of other bioactive components with anti-inflammatory, antioxidant, and anti-cancer properties. As a whole food approach, kale may provide more favorable biologic effects than lutein alone. Findings from this intervention study of kale and lutein in four doses that are relevant to human intakes in a relevant mouse model would provide important evidence of the role of kale and lutein in preventing colonic inflammation and associated neoplasia, help elucidate the underlying molecular mechanisms, and provide a basis for conducting human intervention trials. The demonstration of the benefit of kale and lutein in the prevention of colonic inflammation and colitis-associated colorectal neoplasia from this study would also provide strong support for public health recommendations on increasing consumption of kale and other lutein-rich dark green leafy vegetables. Biomarkers measured in this study may also have broad application in the study of other nutrients and may serve as intermediate endpoints that can be used in future human intervention trials. We have carried out the planned project activities as follows: 1. The kale and lutein intervention studies using the dextran sulfate sodium (DSS)-induced mouse colitis model, including the preparation and animal feeding with diets containing 4 doses of lutein and 4 different amounts of kale power (equivalent to 4 lutein doses), the administration of DSS, weekly clinical colitis evaluations (loose stool, diarrhea, hemoccult testing), weekly body weight measurements, mortality monitoring, and blood and tissue collection of the 260 study mice. As planned, the DSS administration and the kale and lutein interventions for 260 study mice were conducted in two batches (130 female mice as batch one and 130 male mice as batch two) because of large sample size (n=260). Each batch took about 6 months for a total of approximately 12 months. 2. Colonic tissue histopathology fixation, processing, embedding, sectioning, and H & E staining, and histopathological evaluations (inflammation, crypt distortion, aberrant crypt foci, ulceration, erosion, loss of goblet cells, hyperplasia, dysplasia, adenoma, and adenocarcinoma) of the 260 study mice. These project activities took approximately an additional 12 months. 3. HPLC assays of plasma and colonic tissue levels of lutein, lutein isomers, and lutein metabolites and data analyses of the 260 study mice. These project activities further took an additional 6 months. 4. Immunohistochemical staining and microscopic quantification of immunohistochemical staining results of a variety of molecular markers of colonic inflammation of the 260 study mice, data analyses, and the preparation of manuscripts for publication. These project activities are ongoing. While we are making progress in immunohistochemical staining and microscopic quantification of immunohistochemical staining results of molecular markers, these procedures are extremely labor intensive and time consuming. These immunohistochemical staining results of molecular markers are key components of the planned manuscript describing the underlying molecular mechanisms of biologic effects of kale vegetable on the prevention of colonic inflammation. 5. Training of post-docs, graduate students, and laboratory technician. I have delivered science-based knowledge (e.g., design and implementation of animal intervention studies; interpretation and demonstration of animal model experiments; preparation and administration of special animal intervention diets; preparation and administration of DSS for colitis induction; measurements of clinical colitis; animal anesthesia and blood and tissue collection procedures; histopathological procedures; histopathological evaluations; blood and tissue processing and extraction; HPLC analysis procedures; immunohistochemical staining procedures; microscopic quantification of immunohistochemical staining results; data analysis; and data presentation) to post-docs, visiting scientists, and graduate students through laboratory demonstrations and instructions, laboratory meeting discussions, and experiential learning opportunities. 6. Dissemination of study results. I have presented the abstracts and posters of the components of data from this project at large national and international scientific conferences (e.g., Experimental Biology, American Association for Cancer Research) that were attended by broad scientific audiences. The abstracts for these conferences were published in the programs and proceedings, which can reach the general public. Furthermore, I have submitted the findings on the clinical evaluations of colonic inflammation and the findings from histopathological evaluations to the USDA/NIFA AFRI Function and Efficacy of Nutrients, Improved Processing Technologies, and Improving Food Quality Program Directors' Meetings every year throughout the grant period. Conference presentations and publications related to this project are listed below. Liu C, Bronson RT, Wang XD. Dietary lutein and kale intakes modulate colonic inflammation in the DSS mouse model of colitis. 2017 USDA-NIFA Joint Project Director's Meeting - Improving Food Quality and Function and Efficacy of Nutrients. Las Vegas, Nevada, June 24, 2017. Liu C, Bronson RT, Wang XD. Biological effects of lutein and kale on the prevention of colonic inflammation and carcinogenesis. Program and Proceedings of the American Association for Cancer Research Special Conference on Colorectal Cancer: From Initiation to Outcomes. Poster Session A. A31. Page 62. Tampa, FL, September 17 - 20, 2016. Liu C, Bronson RT, Wang XD. Biological effects of kale and lutein on the prevention of colonic inflammation and associated preneoplastic and neoplastic lesions. 2016 USDA/NIFA AFRI Function and Efficacy of Nutrients, Improved Processing Technologies, and Improving Food Quality Program Directors' Meeting. San Diego, CA, April 6, 2016. Liu C, Bronson RT, Wang XD. Biologic Effects of Kale and Lutein on the Prevention of Colonic Inflammation. FY 2015 USDA/NIFA - AFRI/NRI Function and Efficacy of Nutrients/Bioactive Components for Optimal Health, and Improving Food Quality Program Director's Meeting. Chicago, IL, July 10-14, 2015. Liu C, Bronson RT, Wang XD. Effects of Lutein Supplementation on the prevention of colonic inflammation and neoplasia in mice. Experimental Biology 2015. Boston, MA, March 28-April 1, 2015. Liu C, Bronson RT, Wang XD. Effects of Lutein Supplementation on the Prevention of Colonic Inflammation and Neoplasia in Mice. FASEB J April 2015 29:767.3 Liu C, Bronson RT, Wang XD. Dietary lutein and kale intakes inhibit colitis in the DSS mouse model: Clinical findings. Manuscript in preparation. Liu C, Bronson RT, Wang XD. Dietary lutein and kale intakes modulate colonic inflammation in the DSS mouse model of colitis: Histopathological findings. Manuscript in preparation. Liu C, Bronson RT, Wang XD. Biological effects of lutein and kale on the prevention of colonic inflammation and carcinogenesis: the understanding of the underlying molecular mechanisms. Planned manuscript preparation.
Publications
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2016
Citation:
Liu C, Bronson RT, Wang XD. Biological effects of lutein and kale on the prevention of colonic inflammation and carcinogenesis. Program and Proceedings of the American Association for Cancer Research Special Conference on Colorectal Cancer: From Initiation to Outcomes. Poster Session A. A31. Page 62. Tampa, FL, September 17 - 20, 2016.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Liu C, Bronson RT, Wang XD. Dietary lutein and kale intakes modulate colonic inflammation in the DSS mouse model of colitis. 2017 USDA-NIFA Joint Project Director's Meeting - Improving Food Quality and Function and Efficacy of Nutrients. Las Vegas, Nevada, June 24, 2017.
|
Progress 02/01/16 to 01/31/17
Outputs
Target Audience:I have delivered science-based knowledge (e.g., design and implementation of animal intervention studies; interpretation and demonstration of animal model experiments; preparation and administration of special animal intervention diets; preparation and administration of dextran sulfate sodium (DSS) for colitis induction; measurements of clinical colitis; animal anesthesia and blood and tissue collection procedures; histopathological procedures; histopathological evaluations; blood and tissue processing and extraction; HPLC analysis procedures; immunohistochemical staining procedures; microscopic quantification of immunohistochemical staining results; data analysis; and data presentation) to visiting scientists, post-docs, graduate students, and laboratory technician through laboratory demonstrations and instructions, laboratory meeting discussions, and experiential learning opportunities. In addition, I have submitted and presented the abstract and poster of the components of data from this grant to a large national/international scientific conference that was attended by broad scientific audiences (2016 American Association for Cancer Research [AACR] Special Conference on Colorectal Cancer: From Initiation to Outcomes). The abstract for this AACR conference was published in the program and proceedings, which can reach the general public. Furthermore, I have submitted the findings on the clinical evaluations of colonic inflammation (hemoccult and loose stools), which were examined weekly throughout the animal experiments, and the findings from histopathological evaluations (inflammation, ulceration, hyperplasia, dysplasia, and neoplasia) to the 2016 USDA/NIFA AFRI Function and Efficacy of Nutrients, Improved Processing Technologies, and Improving Food Quality Program Directors' Meeting that was held in San Diego, CA on April 6, 2016. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?This study also includes a component of the training of visiting scientists, post-docs, graduate students, and laboratory technician. Through participating in research activities, the trainees have gained hands-on experience in designing and implementing animal intervention studies and in conducting laboratory and histopathological experiment procedures, histopathological evaluations, immunohistochemical staining procedures, and microscopic quantification of immunohistochemical staining results. I have delivered science-based knowledge (e.g., design and implementation of animal intervention studies; interpretation and demonstration of animal model experiments; preparation and administration of special animal intervention diets; preparation and administration of DSS for colitis induction; measurements of clinical colitis; animal anesthesia and blood and tissue collection procedures; histopathological procedures; histopathological evaluations; blood and tissue processing and extraction; HPLC analysis procedures; immunohistochemical staining procedures; microscopic quantification of immunohistochemical staining results; data analysis; and data presentation) to visiting scientists, post-docs, and graduate students through laboratory demonstrations and instructions, laboratory meeting discussions, and experiential learning opportunities. How have the results been disseminated to communities of interest?Through the presentation of the results at national and international scientific conferences attended by broad scientific audiences and through the publication in the journal that reaches the general public. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
Ulcerative colitis, a chronic inflammatory disease, increases risk of colorectal cancer. Lutein, a bioactive food component, is inversely associated with systemic inflammatory markers and colorectal cancer risk in observational studies. The major sources of lutein in the American diet are green leafy vegetables such as kale. Kale is among the most commonly grown vegetables worldwide. Besides lutein, kale contains abundant amounts of other bioactive components with anti-inflammatory, antioxidant, and anti-cancer properties. As a whole food approach, kale may provide more favorable biologic effects than lutein alone. Findings from this intervention study of kale and lutein in four doses that are relevant to human intakes in a relevant mouse model would provide important evidence of the role of kale and lutein in preventing colonic inflammation and associated neoplasia, help elucidate the underlying molecular mechanisms, and provide a basis for conducting human intervention trials. The demonstration of the benefit of kale and lutein in the prevention of colonic inflammation and colitis-associated colorectal neoplasia from this study would also provide strong support for public health recommendations on increasing consumption of kale and other lutein-rich dark green leafy vegetables. Biomarkers measured in this study may also have broad application in the study of other nutrients and may serve as intermediate endpoints that can be used in future human intervention trials. We have carried out the planned project activities as follows: The kale and lutein intervention studies using the dextran sulfate sodium (DSS)-induced mouse colitis model, including the preparation and animal feeding with diets containing 4 doses of lutein and kale power (equivalent to 4 lutein doses), the administration of DSS, regular clinical colitis evaluations (loose stool, diarrhea, hemoccult testing), body weight measurements, mortality monitoring, and blood and tissue collection. As planned, the DSS administration and the kale and lutein interventions for 260 mice were conducted in two batches (130 female mice as batch one and 130 male mice as batch two) because of large sample size (n=260). Each batch took about 6 months for a total of approximately 12 months. Colonic tissue histopathological processing, embedding, sectioning, and staining, and histopathological evaluations (inflammation, ulceration, hyperplasia, dysplasia, adenoma, and adenocarcinoma) of the 260 study mice. These project activities took approximately additional 12 months. Immunohistochemical staining and microscopic quantification of immunohistochemical staining results of a variety of molecular markers of colonic inflammation of the 260 study mice, data analysis, and preparation of manuscripts for publication. These project activities are ongoing.
Publications
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2016
Citation:
Liu C, Bronson RT, Wang XD. Biological effects of lutein and kale on the prevention of colonic inflammation and carcinogenesis. Program and Proceedings of the American Association for Cancer Research Special Conference on Colorectal Cancer: From Initiation to Outcomes. Poster Session A. A31. Page 62. Tampa, FL, September 17 - 20, 2016.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2016
Citation:
Liu C, Bronson RT, Wang XD. Biological effects of kale and lutein on the prevention of colonic inflammation and associated preneoplastic and neoplastic lesions. 2016 USDA/NIFA AFRI Function and Efficacy of Nutrients, Improved Processing Technologies, and Improving Food Quality Program Directors' Meeting. San Diego, CA, April 6, 2016.
|
Progress 02/01/15 to 01/31/16
Outputs
Target Audience:I have delivered science-based knowledge (e.g., design and implementation of animal intervention studies; interpretation and demonstration of animal model experiments; preparation and administration of special animal intervention diets; preparation and administration of dextran sulfate sodium (DSS) for colitis induction; measurements of clinical signs of colitis; animal anesthesia and blood and tissue collection procedures; histopathological procedures; histopathological evaluations; blood and tissue processing and extraction; and HPLC analysis procedures) to visiting scientists, post-docs, graduate students, and laboratory technician through laboratory demonstrations and instructions, laboratory meeting discussions, and experiential learning opportunities. I have also submitted and presented the abstract and poster of the preliminary data for this grant application to a large national/international scientific conference (Experimental Biology 2015), which was attended by broad scientific audiences. The abstract for the Experimental Biology 2015 was published in the FASEB Journal that reaches the general public (Liu C,et al. FASEB JApril 201529:767.3). Furthermore, I have presented the findings on the clinical evaluations of colonic inflammation (hemoccult and loose stools), which were conducted weekly throughout the animal experiments, at the FY 2015 USDA/NIFA - AFRI/NRI Function and Efficacy of Nutrients/Bioactive Components for Optimal Health, and Improving Food Quality Program Director's Meeting that was held in Chicago, IL on July 10, 2015. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?This study also includes a component of the training of visiting scientists, post-docs, graduate students, and laboratory technician. Through participating in research activities, the trainees have gained hands-on experience in designing and implementing animal intervention studies and in conducting laboratory and histopathological experiment procedures and histopathological evaluations. I have delivered science-based knowledge (e.g., design and implementation of animal intervention studies; interpretation and demonstration of animal model experiments; preparation and administration of special animal intervention diets; preparation and administration of DSS for colitis induction; measurements of clinical signs of colitis; animal anesthesia and blood and tissue collection procedures; histopathological procedures; histopathological evaluations; blood and tissue processing and extraction; and HPLC analysis procedures) to visiting scientists, post-docs, and graduate students through laboratory demonstrations and instructions, laboratory meeting discussions, and experiential learning opportunities. How have the results been disseminated to communities of interest?Through the presentation of the results at scientific conferences attended by broad scientific audiences and through the publication in the journal that reaches the general public. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
Ulcerative colitis, a chronic inflammatory disease, increases risk of colorectal cancer. Lutein, a bioactive food component, is inversely associated with systemic inflammatory markers and colorectal cancer risk in observational studies. The major sources of lutein in the American diet are green leafy vegetables such as kale. Kale is among the most commonly grown vegetables worldwide. Besides lutein, kale contains abundant amounts of other bioactive components with anti-inflammatory, antioxidant, and anti-cancer properties. As a whole food approach, kale may provide more favorable biologic effects than lutein alone. Findings from this intervention study of kale and lutein in four doses that are relevant to human intakes in a relevant mouse model would provide important evidence of the role of kale and lutein in preventing colonic inflammation and associated neoplasia, help elucidate the underlying molecular mechanisms, and provide a basis for conducting human intervention trials. The demonstration of the benefit of kale and lutein in the prevention of colonic inflammation and colitis-associated colorectal neoplasia from this study would also provide strong support for public health recommendations on increasing consumption of kale and other lutein-rich dark green leafy vegetables. Biomarkers measured in this study may also have broad application in the study of other nutrients and may serve as intermediate endpoints that can be used in future human intervention trials. We have carried out the planned project activities as follows: The kale and lutein intervention studies using the dextran sulfate sodium (DSS)-induced mouse colitis model, including the preparation and animal feeding with diets containing 4 doses of lutein and kale power (equivalent to 4 lutein doses), the administration of DSS, regular clinical evaluations of colitis (loose stool, diarrhea, hemoccult testing), body weight measurements, mortality monitoring, and blood and tissue collection. As planned, the DSS administration and the kale and lutein interventions for 264 mice were conducted in two batches (134 female mice as batch one and 130 male mice as batch two) because of large sample size. Each batch took about 6 months for a total of approximately 12 months. Colonic tissue histopathological processing, embedding, sectioning, and staining, and histopathological evaluations (e.g., inflammation, ulceration, hyperplasia, dysplasia, and neoplasia) of the 264 study mice. These project activities took approximately additional 12 months.
Publications
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2015
Citation:
Liu C, Bronson RT, Wang XD. Biologic Effects of Kale and Lutein on the Prevention of Colonic Inflammation. FY 2015 USDA/NIFA AFRI/NRI Function and Efficacy of Nutrients/Bioactive Components for Optimal Health, and Improving Food Quality Program Director's Meeting. Chicago, IL, July 10, 2015.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2015
Citation:
Liu C, Bronson RT, Wang XD. Effects of Lutein Supplementation on the Prevention of Colonic Inflammation and Neoplasia in Mice. FASEB J April 2015 29:767.3
|
Progress 02/01/14 to 01/31/15
Outputs
Target Audience: During this reporting period, the planned project activities for year one have been completed. With respect to target audience, I have delivered science-based knowledge (e.g., design and implementation of animal intervention studies; interpretation and demonstration of animal model experiments; preparation and administration of special animal intervention diets; preparation and administration of dextran sulfate sodium for colitis induction; measurements of clinical colitis; animal anesthesia procedure; blood and tissue collection procedures; histopathological procedures; blood and tissue processing and extraction; and HPLC analysis procedures) to visiting scientists, post-docs, and graduate students through laboratory demonstrations and instructions, laboratory meeting discussions, and experiential learning opportunities. In addition, I have submitted the abstract of the preliminary data for this grant application to a large international/national scientific conference (Experimental Biology 2015), which will be attended by broad scientific audiences. The abstract has been accepted by the conference and will be published in a proceeding that reaches the general public. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided? This study also includes a component of the training of visiting scientists, post-docs, and graduate students. Through participating in research activities, the trainees have gained hands-on experience in designing and implementing animal intervention studies and in conducting laboratory and histopathological experiment procedures. During this reporting period, I have delivered science-based knowledge (e.g., design and implementation of animal intervention studies; interpretation and demonstration of animal model experiments; preparation and administration of special animal intervention diets; preparation and administration of DSS for colitis induction; measurements of clinical colitis; animal anesthesia procedure; blood and tissue collection procedures; histopathological procedures; blood and tissue processing and extraction; and HPLC analysis procedures) to visiting scientists, post-docs, and graduate students through laboratory demonstrations and instructions, laboratory meeting discussions, and experiential learning opportunities. How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
Ulcerative colitis, a chronic inflammatory disease, increases risk of colorectal cancer. Lutein, a bioactive food component, is inversely associated with systemic inflammatory markers and colorectal cancer risk in observational studies. The major sources of lutein in the American diet are green leafy vegetables such as kale. Kale is among the most commonly grown vegetables worldwide. Besides lutein, kale contains abundant amounts of other bioactive components with anti-inflammatory, antioxidant, and anti-cancer properties. As a whole food approach, kale may provide more favorable biologic effects than lutein alone. Findings from this intervention study of kale and lutein in four doses that are relevant to human intakes in a relevant mouse model will provide important evidence of the role of kale and lutein in preventing colonic inflammation and associated neoplasia, help elucidate the underlying molecular mechanisms, and provide a basis for conducting human intervention trials. The demonstration of the benefit of kale and lutein in the prevention of colonic inflammation and colitis-associated colorectal neoplasia from this study would also provide strong support for public health recommendations on increasing consumption of kale and other lutein-rich dark green leafy vegetables. Biomarkers measured in this study may also have broad application in the study of other nutrients and may serve as intermediate endpoints that can be used in future human intervention trials. During this reporting period, we have completed the planned project activities for year one – i.e., kale and lutein intervention studies using the dextran sulfate sodium (DSS)-induced mouse colitis model, including the preparation and animal feeding with diets containing 4 doses of lutein and kale power (equivalent to 4 lutein doses), the administration of DSS, regular clinical colitis evaluations (loose stool, diarrhea, hemoccult testing), body weight measurements, mortality monitoring, blood and tissue collection, and tissue histopathological processing. As planned, the DSS administration and the kale and lutein interventions for 260 mice were conducted in two batches (130 female mice as batch one and 130 male mice as batch two) because of large sample size (n=260). Each batch took about 6 months for a total of approximately 12 months in year one.
Publications
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2015
Citation:
Liu C, Bronson RT, Wang XD. Lutein Supplementation on the Prevention of Colonic Inflammation and Neoplasia in Mice. Experimental Biology 2015. Boston, MA, March 28 - April 1, 2015.
|
|