Deficiency of peroxisomal NUDT7 stimulates de novo lipogenesis in hepatocytes.

Here, we found that heterozygous null of peroxisomal Nudt7 (Nudt7 +/- ) induced the typical NAFLD features, i.e. increased levels of hepatic triglyceride (TG) and fatty acid (FA), infiltration of inflammatory cells, impaired glucose tolerance and insulin sensitivity, and stimulation of lipolysis from adipose tissue. Particularly, in Nudt7 +/- hepatocytes, de novo lipogenesis (DNL) was significantly increased. Ingenuity pathway analysis (IPA) and KEGG pathway analysis of RNA sequencing data suggested the activation of PPAR signaling in the liver of Nudt7 +/- mice. Moreover, accumulation of palmitic acid in Nudt7 +/- hepatocyte increased the level of H3K4me3 on the promoters of PPARγ resulting in the activation of PPARγ and induced the DNL in the hepatocytes of Nudt7 +/- mice. Moreover, we found that liraglutide significantly reduced typical NAFLD features induced by NUDT7 deficiency. Our data suggest that dysregulation of peroxisomal NUDT7 is responsible for upregulation of hepatic DNL by accumulation of palmitic acid and PPARγ activation.

Comparative evaluation of Nanopore polishing tools for microbial genome assembly and polishing strategies for downstream analysis.

Assembling high-quality microbial genomes using only cost-effective Nanopore long-read systems such as Flongle is important to accelerate research on the microbial genome and the most critical point for this is the polishing process. In this study, we performed an evaluation based on BUSCO and Prokka gene prediction in terms of microbial genome assembly for eight state-of-the-art Nanopore polishing tools and combinations available. In the evaluation of individual tools, Homopolish, PEPPER, and Medaka demonstrated better results than others. In combination polishing, the second round Homopolish, and the PEPPER × medaka combination also showed better results than others. However, individual tools and combinations have specific limitations on usage and results. Depending on the target organism and the purpose of the downstream research, it is confirmed that there remain some difficulties in perfectly replacing the hybrid polishing carried out by the addition of a short-read. Nevertheless, through continuous improvement of the protein pores, related base-calling algorithms, and polishing tools based on improved error models, a high-quality microbial genome can be achieved using only Nanopore reads without the production of additional short-read data. The polishing strategy proposed in this study is expected to provide useful information for assembling the microbial genome using only Nanopore reads depending on the target microorganism and the purpose of the research.

NUDT7 Loss Promotes KrasG12D CRC Development.

Studies have suggested that dysregulation of peroxisomal lipid metabolism might play an important role in colorectal cancer (CRC) development. Here, we found that KrasG12D-driven CRC tumors demonstrate dysfunctional peroxisomal b-oxidation and identified Nudt7 (peroxisomal coenzyme A diphosphatase NUDT7) as one of responsible peroxisomal genes. In KrasG12D-driven CRC tumors, the expression level of Nudt7 was significantly decreased. Treatment of azoxymethane/dextran sulfate sodium (AOM/DSS) into Nudt7 knockout (Nudt7-/-) mice significantly induced lipid accumulation and the expression levels of CRC-related genes whereas xenografting of Nudt7-overexpressed LS-174T cells into mice significantly reduced lipid accumulation and the expression levels of CRC-related genes. Ingenuity pathway analysis of microarray using the colon of Nudt7-/- and Nudt7+/+ mice treated with AOM/DSS suggested Wnt signaling as one of activated signaling pathways in Nudt7-/- colons. Upregulated levels of ß-catenin were observed in the colons of KrasG12D and AOM/DSS-treated Nudt7-/- mice and downstream targets of ß-catenin such as Myc, Ccdn1, and Nos2, were also significantly increased in the colon of Nudt7-/- mice. We observed an increased level of palmitic acid in the colon of Nudt7-/- mice and attachment of palmitic acid-conjugated chitosan patch into the colon of mice induced the expression levels of b-catenin and CRC-related genes. Overall, our data reveal a novel role for peroxisomal NUDT7 in KrasG12D-driven CRC development.

Bromelain effectively suppresses Kras-mutant colorectal cancer by stimulating ferroptosis.

Here, we investigated the possible anti-cancer properties of bromelain in Kras mutant human colorectal carcinoma cell lines and a mouse model harboring a Kras mutation. Cell growth and proliferation were significantly reduced in the Kras mutant colorectal carcinoma cell lines following treatment with 50 µg/mL bromelain as assessed by crystal violet staining and a proliferation assay. To identify the molecules responsible for this action, the expression levels of genes involved in signaling pathways and miRNAs were analyzed by real-time PCR. Among the genes tested, down-regulation of ACSL-4 and up-regulation of miRNAs targeting ASCL-4 were observed in Caco2 cells. Compared to the Kras wild-type colorectal carcinoma cell lines, Kras mutant colorectal carcinoma cell lines exhibited a remarkably up-regulated expression of ACSL-4, which is responsible for ferroptosis sensitivity. Moreover, the knockdown of ACSL-4 by a specific shRNA inhibited erastin-induced ferroptosis in Kras mutant DLD-1 cells as assessed by propidium iodide staining and lipid reactive oxygen species measurement. Our findings indicate that bromelain effectively exerts cytotoxic effects in Kras mutant colorectal cancer cells compared to in Kras wild-type colorectal cancer cells. Differential expression of ACSL-4 is responsible for the differential action of bromelain in regulating ferroptotic cell death.

Suppression of ABCD2 dysregulates lipid metabolism via dysregulation of miR-141:ACSL4 in human osteoarthritis.

Even though increasing evidence indicates the importance of peroxisomal lipid metabolism in regulating biological and pathological events, its involvement in cartilage development has not been well studied. Here, we identified the importance of peroxisomal function, particularly the functional integrity of ABCD2, in the pathogenesis of osteoarthritis (OA). Knockdown of ABCD2 in OA chondrocytes induced the accumulation of very long chain fatty acids (VLCFAs) and apoptotic cell death. Moreover, knockdown of ABCD2 altered profiles of miRNAs that affect the expression level of ACSL4, a known direct regulator of lipid metabolism. Suppression of ACSL4 in human chondrocytes-induced VLCFA accumulation, MMP-13 expression, and apoptotic cell death. In vivo morph-down of the ACSL4 homologue in zebrafish resulted in significant defects in cartilage development and in vivo knockdown of ACSL4 in cartilage tissue of an OA model mice promoted severe cartilage degradation. In summary, to the best of our knowledge, this is the first report suggesting that the regulatory network among peroxisomal ABCD2:ACSL4:VLCFA serves as a novel regulator of cartilage homeostasis, and these data may provide novel insights into the role of peroxisomal fatty acid metabolism in pathogenesis of human OA. SIGNIFICANCE OF THE STUDY: Our study indicates that peroxisomal dysfunction is closely related to OA pathogenesis. Particularly, the functional integrity of ABCD2 may play an important role in OA pathogenesis via the accumulation of VLCFAs and stimulation of apoptotic death through altering profiles of miRNAs that target ACSL4. Our findings suggest that targeting the regulatory network among the peroxisomal ABCD2:ACSL4:VLCFA axis may provide a new potential therapeutic strategy for OA pathogenesis.

Nurse Case Managers' Experiences on Case Management for Long-term Hospitalization in Korea.

PURPOSE: The implementation of case management for long-term hospitalization use has been approved for controlling medical cost increases in other countries. But, introduction of the case management in Korea has created issues that hinder its effective operation. This qualitative study aimed to obtain further understanding of the issues surrounding the management of Medical Aid beneficiaries' use of long-term hospitalization from the case managers' perspectives and to provide suggestions for successful case management. METHODS: Thematic analysis was employed to analyze the data. Medical Aid case managers with 3 or more years of case management experience were recruited from urban, suburban, and rural regions. Data were collected through in-depth interviews: 12 nurse case managers participated in focus group interviews and 11 participated in individual one-on-one interviews. RESULTS: Four major themes emerged: on-site obstacles that hinder work progress; going in an opposite direction; ambiguous position of case managers; and work-related emotions. Eleven subthemes were discovered: chasing potential candidates; becoming an enemy; discharging patients who have nowhere to go; welfare-centered national policies increasing medical costs; Medical Aid Program that encourages hospitalization; misuse of hospitalization; feeling limited; working without authority; fulfilling the expected role; fretting about social criticism; and feeling neglected and unprotected. CONCLUSION: The findings highlight the complexity and ambiguity of the issues faced by case managers. Successful management of Medical Aid resources requires the orchestrated efforts and collaboration of multiple stakeholders. More systematized support and resources for nurse case managers are essential to fully implement this nursing innovation in Korea.

Case management for medical aid beneficiaries in Korea: findings from case-control study.

PURPOSE: This study was to evaluate effects of case management provided for 7 months for medical aid in Korea. METHODS: This study was a retrospective comparative study using secondary data analysis. Data from two pre-existing survey were reanalyzed. The data were collected through door to-door interviews using the structured questionnaire. For the medical service use, claims data from the Korea National Health Insurance Corporation was used. Subjects were 73 in the intervention group and 118 in the control group. RESULTS: There was no significant change in the intervention group in self-care ability (p = .296), medication adherence (p = .194) or quality of life (p = .903) compared to those of the control group. For hospital visiting days, it appeared to decrease in the intervention group (p = .038) but with no significant difference from that of the control group (p = .157). Neither were there significant differences in medical expenditures (p = .605). CONCLUSION: Although the effect of case management in this study appeared extremely limited, the short intervention period and characteristics of the medical aid beneficiaries and the limit of controlling only the demand side were discussed as factors to be considered. Nurses have been carrying out professional roles in case management in Korea. However more efforts are needed to develop case management as an area for nursing specialization.

Stroke patients' experiences of sharing rooms with dementia patients in a nursing home.

BACKGROUND: The mixed units that place lucid and dementia patients in same rooms have been viewed to benefit the dementia patients. However, many studies report negative attitudes of lucid residents towards mixed units, and there is a scarcity of research which explores the experiences of lucid residents while sharing rooms with the dementia patients in extended care homes. Currently many special care nursing facilities have mixed units in Korea, suggesting a need to examine their effects especially on cognitively lucid patients. OBJECTIVE: To explore lived experiences of stroke patients who were sharing rooms with patients with dementia in a nursing home. DESIGN: It was a qualitative study applying a phenomenological method to explore the experiences of stroke patients. SETTINGS: Data were collected in a specialized nursing home in Korea. The nursing home provides free medical and nursing care to persons suffering either from dementia or stroke. PARTICIPANTS: Fourteen participants without cognitive deficit and who were sharing rooms with dementia patients were recruited through a purposive sampling. METHOD: In-depth interviews RESULTS: Stroke patients sharing rooms with dementia patients were being seriously affected by intense, deeply disturbing, and persistent experiences. The experiences themselves seemed to evolve over time as each patient struggled on one's own to try to make sense out of what were happening. The stroke patients ended up having a sense of resignation and anger realizing that they had no power to change the policy or the situation. The stroke patients also were distraught about what were happening to themselves - change of their own character, continuous fear of becoming demented, and becoming to devalue life. They also became indifferent to others, and seemed to have lost motivation for activity resulting in a decreased or low activity level. Several personal and environmental factors were identified that tended to increase the level of suffering. We suggest that the whole concept of mixed units require further exploration, and there is a need for a comprehensive staff education program to help the staff become aware of the problems and provide support to patients. Orientation of stroke patients regarding dementia is also suggested.

A study of elder abuse in Korea.

This study investigates the state of elder abuse in Korea, and its related factors in a population-based survey. A total of 15,230 persons were interviewed at their homes in 1999. The rate of old people who experienced any one category of abuse was 6.3%, and emotional abuse was the most frequent while physical abuse was least prevalent. The experience of abuse seemed to be associated with personal characteristics such as age, gender, educational level, and economic dependency as well as the physical and mental health status. In addition, family characteristics such as the type of household, the family's economic level, and the quality of family relations were found to be associated with the presence of abuse.