Carotenoid composition and carotenogenic gene expression during Ipomoea petal development

Japanese morning glory (Ipomoea nil) is a representative plant lacking a yellow-flowered cultivar, although a few wild Ipomoea species contain carotenoids in their petals such as Ipomoea sp. (yellow petals) and I. obscura (pale-yellow petals). In the present study, carotenoid composition and the expression patterns of carotenogenic genes during petal development were compared among I. nil, I. obscura, and Ipomoea sp. to identify the factors regulating carotenoid accumulation in Ipomoea plant petals. In the early stage, the carotenoid composition in petals of all the Ipomoea plants tested was the same as in the leaves mainly showing lutein, violaxanthin, and β-carotene (chloroplast-type carotenoids). However, in fully opened flowers, chloroplast-type carotenoids were entirely absent in I. nil, whereas they were present in trace amounts in the free form in I. obscura. At the late stage of petal development in Ipomoea sp., the majority of carotenoids were β-cryptoxanthin, zeaxanthin, and β-carotene (chromoplast-type carotenoids). In addition, most of them were present in the esterified form. Carotenogenic gene expression was notably lower in I. nil than in Ipomoea sp. In particular, β-ring hydroxylase (CHYB) was considerably suppressed in petals of both I. nil and I. obscura. The CHYB expression was found to be significantly high in the petals of Ipomoea sp. during the synthesis of chromoplast-type carotenoids. The expression levels of carotenoid cleavage genes (CCD1 and CCD4) were not correlated with the amount of carotenoids in petals. These results suggest that both I. obscura and I. nil lack the ability to synthesize chromoplast-type carotenoids because of the transcriptional down-regulation of carotenogenic genes. CHYB, an enzyme that catalyses the addition of a hydroxyl residue required for esterification, was found to be a key enzyme for the accumulation of chromoplast-type carotenoids in petals

A region-based palliative care intervention trial using the mixed-method approach: Japan OPTIM study

<p>Abstract</p> <p>Background</p> <p>Disseminating palliative care is a critical task throughout the world. Several outcome studies explored the effects of regional palliative care programs on a variety of end-points, and some qualitative studies investigated the process of developing community palliative care networks. These studies provide important insights into the potential benefits of regional palliative care programs, but the clinical implications are still limited, because: 1) many interventions included fundamental changes in the structure of the health care system, and, thus, the results would not be applicable for many regions where structural changes are difficult or unfeasible; 2) patient-oriented outcomes were not measured or explored only in a small number of populations, and interpretation of the results from a patient's view is difficult; and 3) no studies adopted a mixed-method approach using both quantitative and qualitative methodologies to interpret the complex phenomenon from multidimensional perspectives.</p> <p>Methods/designs</p> <p>This is a mixed-method regional intervention trial, consisting of a pre-post outcome study and qualitative process studies. The primary aim of the pre-post outcome study is to evaluate the change in the number of home deaths, use of specialized palliative care services, patient-reported quality of palliative care, and family-reported quality of palliative care after regional palliative care intervention. The secondary aim is to explore the changes in a variety of outcomes, including patients' quality of life, pain intensity, family care burden, and physicians' and nurses' knowledge, difficulties, and self-perceived practice. Outcome measurements used in this study include the Care Evaluation Scale, Good Death Inventory, Brief pain Inventory, Caregiving Consequence Inventory, Sense of Security Scale, Palliative Care Knowledge test, Palliative Care Difficulties Scale, and Palliative Care Self-reported Practice Scale. Study populations are a nearly representative sample of advanced cancer patients, bereaved family members, physicians, and nurses in the region.</p> <p>Qualitative process studies consist of 3 studies with each aim: 1) to describe the process in developing regional palliative care in each local context, 2) to understand how and why the regional palliative care program led to changes in the region and to propose a model for shaping regional palliative care, and 3) to systemically collect the barriers of palliative care at a regional level and potential resolutions. The study methodology is a case descriptive study, a grounded theory approach based on interviews, and a content analysis based on systemically collected data, respectively.</p> <p>Discussion</p> <p>This study is, to our knowledge, one of the most comprehensive evaluations of a region-based palliative care intervention program. This study has 3 unique aspects: 1) it measures a wide range of outcomes, including quality of care and quality of life measures specifically designed for palliative care populations, whether patients died where they actually preferred, the changes in physicians and nurses at a regional level; 2) adopts qualitative studies along with quantitative evaluations; and 3) the intervention is without a fundamental change in health care systems. A comprehensive understanding of the findings in this study will contribute to a deeper insight into how to develop community palliative care.</p> <p>Trial Registration</p> <p>UMIN Clinical Trials Registry (UMIN-CTR), Japan, UMIN000001274.</p

Chemical- and Drug-Induced Allergic, Inflammatory, and Autoimmune Diseases Via Haptenation

Haptens are small molecules that only elicit an immune response when bound to proteins. Haptens initially bind to self-proteins and activate innate immune responses by complex mechanisms via inflammatory cytokines and damage-associated molecular patterns and the subsequent upregulation of costimulatory signals such as cluster of differentiation 86 (CD86) on dendritic cells. Subsequent interactions between CD86 and CD28 on T cells are critically important for properly activating naive T cells and inducing interleukin 2 production, leading to the establishment of adaptive immunity via effector and memory T cells. Accumulating evidence revealed the involvement of haptens in the development of various autoimmune-like diseases such as allergic, inflammatory, and autoimmune diseases including allergic contact dermatitis, atopy, asthma, food allergy, inflammatory bowel diseases, hemolytic anemia, liver injury, leukoderma, and even antitumor immunity. Therefore, the development of in vitro testing alternatives to evaluate in advance whether a substance might lead to the development of these diseases is highly desirable. This review summarizes and discusses recent advances in chemical- and drug-induced allergic, inflammatory, and autoimmune diseases via haptenation and the possible molecular underlying mechanisms, as well as in vitro testing alternatives to evaluate in advance whether a substance might cause the development of these diseases