Purpose: Metabolic diseases share common risk factors, requiring the development of therapeutic agents with multi-target effects. Although the ameliorating effects of Porphyra tenera ethanol extract (PTE) have been reported on some individual metabolic disorders, studies addressing various other metabolic diseases are still limited. This study investigated the ameliorating effects of PTE supplementation for 12 weeks on obesity, dyslipidemia, and hepatic lipid metabolism in high-fat diet (HFD)-induced obese mice and its molecular mechanisms. Methods: Male C57BL/6 mice (n = 12/in each group) were divided into six groups for 12 weeks: control, HFD, chow diet + 1% porphyran, chow diet + 4% porphyran, HFD + 1% porphyran (HPYP-L), and HFD + 4% porphyran (HPYP-H). To confirm the attenuation of metabolic disease in vivo, mice in the HFD, HPYP-L and HPYP-H groups were fed 60% HFD to induce obesity. PTE was prepared using ethanol and dissolved in drinking water to concentrations of 1% and 4% porphyran. After 12 weeks of free PTE intake, body weight measurement, serum analysis, histopathological analysis, real-time quantitative polymerase chain reaction, and Western blot analysis of liver tissues were performed for comparative evaluation. Results: After 12 weeks, the HPYP-L and HPYP-H groups showed a decreased body weight, improved blood lipids, and reduced hepatic lipid droplet accumulation vs. the HFD group.Liver acetyl-CoA carboxylase, was suppressed in the HPYP-L group vs. the HFD group.The B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 protein and messenger RNA (mRNA) level ratio in the liver decreased after PTE intake, indicating inhibition of apoptosis.Interleukin-1 beta mRNA expression in the liver was reduced in the HPYP-L group vs. the HFD group. In the liver, lower protein carbonylation levels in the HPYP-H group indicated reduced oxidative stress, while the increased mitochondrial DNAuclear DNA ratio indicated improved mitochondrial function. Conclusion PTE protects against diet-induced metabolic disorders and could be a potential agent for the prevention and treatment of metabolic diseases.

Purpose: Metabolic diseases share common risk factors, requiring the development of therapeutic agents with multi-target effects. Although the ameliorating effects of Porphyra tenera ethanol extract (PTE) have been reported on some individual metabolic disorders, studies addressing various other metabolic diseases are still limited. This study investigated the ameliorating effects of PTE supplementation for 12 weeks on obesity, dyslipidemia, and hepatic lipid metabolism in high-fat diet (HFD)-induced obese mice and its molecular mechanisms. Methods: Male C57BL/6 mice (n = 12/in each group) were divided into six groups for 12 weeks: control, HFD, chow diet + 1% porphyran, chow diet + 4% porphyran, HFD + 1% porphyran (HPYP-L), and HFD + 4% porphyran (HPYP-H). To confirm the attenuation of metabolic disease in vivo, mice in the HFD, HPYP-L and HPYP-H groups were fed 60% HFD to induce obesity. PTE was prepared using ethanol and dissolved in drinking water to concentrations of 1% and 4% porphyran. After 12 weeks of free PTE intake, body weight measurement, serum analysis, histopathological analysis, real-time quantitative polymerase chain reaction, and Western blot analysis of liver tissues were performed for comparative evaluation. Results: After 12 weeks, the HPYP-L and HPYP-H groups showed a decreased body weight, improved blood lipids, and reduced hepatic lipid droplet accumulation vs. the HFD group.Liver acetyl-CoA carboxylase, was suppressed in the HPYP-L group vs. the HFD group.The B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 protein and messenger RNA (mRNA) level ratio in the liver decreased after PTE intake, indicating inhibition of apoptosis.Interleukin-1 beta mRNA expression in the liver was reduced in the HPYP-L group vs. the HFD group. In the liver, lower protein carbonylation levels in the HPYP-H group indicated reduced oxidative stress, while the increased mitochondrial DNAuclear DNA ratio indicated improved mitochondrial function. Conclusion PTE protects against diet-induced metabolic disorders and could be a potential agent for the prevention and treatment of metabolic diseases.

Purpose: Metabolic diseases share common risk factors, requiring the development of therapeutic agents with multi-target effects. Although the ameliorating effects of Porphyra tenera ethanol extract (PTE) have been reported on some individual metabolic disorders, studies addressing various other metabolic diseases are still limited. This study investigated the ameliorating effects of PTE supplementation for 12 weeks on obesity, dyslipidemia, and hepatic lipid metabolism in high-fat diet (HFD)-induced obese mice and its molecular mechanisms. Methods: Male C57BL/6 mice (n = 12/in each group) were divided into six groups for 12 weeks: control, HFD, chow diet + 1% porphyran, chow diet + 4% porphyran, HFD + 1% porphyran (HPYP-L), and HFD + 4% porphyran (HPYP-H). To confirm the attenuation of metabolic disease in vivo, mice in the HFD, HPYP-L and HPYP-H groups were fed 60% HFD to induce obesity. PTE was prepared using ethanol and dissolved in drinking water to concentrations of 1% and 4% porphyran. After 12 weeks of free PTE intake, body weight measurement, serum analysis, histopathological analysis, real-time quantitative polymerase chain reaction, and Western blot analysis of liver tissues were performed for comparative evaluation. Results: After 12 weeks, the HPYP-L and HPYP-H groups showed a decreased body weight, improved blood lipids, and reduced hepatic lipid droplet accumulation vs. the HFD group.Liver acetyl-CoA carboxylase, was suppressed in the HPYP-L group vs. the HFD group.The B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 protein and messenger RNA (mRNA) level ratio in the liver decreased after PTE intake, indicating inhibition of apoptosis.Interleukin-1 beta mRNA expression in the liver was reduced in the HPYP-L group vs. the HFD group. In the liver, lower protein carbonylation levels in the HPYP-H group indicated reduced oxidative stress, while the increased mitochondrial DNAuclear DNA ratio indicated improved mitochondrial function. Conclusion PTE protects against diet-induced metabolic disorders and could be a potential agent for the prevention and treatment of metabolic diseases.

Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (Mpro ) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in Mpro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro, there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the Mpro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC50 values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.

Background: Highly pathogenic avian influenza viruses (HPAIVs) is an extremely contagious and high mortality rates in chickens resulting in substantial economic impact on the poultry sector. Therefore, it is necessary to elucidate the pathogenic mechanism of HPAIV for infection control. Objective: Gene set enrichment analysis (GSEA) can effectively avoid the limitations of subjective screening for differential gene expression. Therefore, we performed GSEA to compare HPAI-infected resistant and susceptible Ri chicken lines. Methods: The Ri chickens Mx(A)/BF2(B21) were chosen as resistant, and the chickens Mx(G)/ BF2(B13) were selected as susceptible by genotyping the Mx and BF2 genes. The tracheal tissues of HPAIV H5N1 infected chickens were collected for RNA sequencing followed by GSEA analysis to define gene subsets to elucidate the sequencing results. Results: We identified four differentially expressed pathways, which were immune-related pathways with a total of 78 genes. The expression levels of cytokines (IL-1β, IL-6, IL-12), chemokines (CCL4 and CCL5), type interferons and their receptors (IFN-β, IFNAR1, IFNAR2, and IFNGR1), Jak-STAT signaling pathway genes (STAT1, STAT2, and JAK1), MHC class I and II and their co-stimulatory molecules (CD80, CD86, CD40, DMB2, BLB2, and B2M), and interferon stimulated genes (EIF2AK2 and EIF2AK1) in resistant chickens were higher than those in susceptible chickens. Conclusions Resistant Ri chickens exhibit a stronger antiviral response to HPAIV H5N1 compared with susceptible chickens. Our findings provide insights into the immune responses of genetically disparate chickens against HPAIV.

Background: Highly pathogenic avian influenza virus (HPAIV) is considered a global threat to both human health and the poultry industry. MicroRNAs (miRNA) can modulate the immune system by affecting gene expression patterns in HPAIV-infected chickens. Objectives: To gain further insights into the role of miRNAs in immune responses against H5N1 infection, as well as the development of strategies for breeding disease-resistant chickens, we characterized miRNA expression patterns in tracheal tissues from H5N1-infected Ri chickens. Methods: miRNAs expression was analyzed from two H5N1-infected Ri chicken lines using small RNA sequencing. The target genes of differentially expressed (DE) miRNAs were predicted using miRDB. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were then conducted. Furthermore, using quantitative real-time polymerase chain reaction, we validated the expression levels of DE miRNAs (miR-22-3p, miR-146b-3p, miR-27b-3p, miR-128-3p, miR-2188-5p, miR-451, miR-205a, miR-203a, miR-21-3p, and miR-200a-3p) from all comparisons and their immune-related target genes. Results: A total of 53 miRNAs were significantly expressed in the infection samples of the resistant compared to the susceptible line. Network analyses between the DE miRNAs and target genes revealed that DE miRNAs may regulate the expression of target genes involved in the transforming growth factor-beta, mitogen-activated protein kinase, and Toll-like receptor signaling pathways, all of which are related to influenza A virus progression. Conclusions Collectively, our results provided novel insights into the miRNA expression patterns of tracheal tissues from H5N1-infected Ri chickens. More importantly, our findings offer insights into the relationship between miRNA and immune-related target genes and the role of miRNA in HPAIV infections in chickens.

BACKGROUND/OBJECTIVES: A dietary restriction on the intake of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) has been reported to be effective in the treatment of gastrointestinal (GI) tract complications. Enteral nutrition (EN) is widely used for patients who cannot obtain their nutritional requirements orally, but many studies have reported EN complications, especially diarrhea, in up to 50% of patients. SUBJECTS/METHODS: We performed a single-center, non-randomized, controlled trial to determine the effects of a low-FODMAP enteral formula on GI complications in patients in intensive care units (ICUs). Patients in the ICU who needed EN (n = 66) were alternately assigned to the low-FODMAP group (n = 33) or the high-FODMAP group (n = 33). RESULTS: Anthropometric and biochemical parameters were measured, and stool assessment was performed using King's Stool Chart. We excluded patients who received laxatives, GI motility agents, proton pump inhibitors, antifungal agents, and antibiotics other than β-lactams. There were no differences in GI symptoms during 7 days of intervention, including bowel sound, abdominal distension, and vomiting between the 2 groups. However, diarrhea was more frequent in the high-FODMAP group (7/33 patients) than the lowFODMAP group (1/33 patients) (P = 0.044). CONCLUSIONS Our results suggest that a low-FODMAP enteral formula may be a practical therapeutic approach for patients who exhibit enteral formula complications. Our study warrants further randomized clinical trials and multicenter trials.

Purpose: In this study, we examined change in the number of cataract surgeries from 2013 to 2018, since the implementation of institutional changes in 2012, and the introduction of diagnosis-related groups (DRGs) and a gradual reduction in selective-medical expenses from 2014. Methods: Based on data from the main surgery statistical yearbook provided by the Korea National Health Insurance Service (KNHIS), we extracted the number of cataract surgeries nationwide by year from 2013 to 2018. Data were divided by sex, age, regions, and level of healthcare providers in an effort to understand changes that occurred in the number of cataract surgeries and the reasons for these changes. Statistical analysis was carried out using joint point regression. Results: The total number of cataract surgeries per 100,000 people increased by 32.9% over the six-year period, with an annual average increase of 5.9%. Females (58.0-59.2%) had more cataract surgeries than males (40.8-42.0%). Additionally, the number of cataract surgeries per 100,000 people rose over the six-year time frame for those aged under 40 years, and for those in their 40s, 50s, and 60s. In terms of regions and patients’ residence, urban areas such as Seoul, Pusan, and Daegu showed an increase in surgeries performed; most provinces, however, with the exception of Jeju Island, indicated a relative decline in cataract surgeries. There was no difference in the number of cataract surgeries performed over the six-year period in terms of the level of healthcare providers. Conclusions The number of cataract surgeries per 100,000 people rose over the six-year period between 2013 and 2018. By region, an increasing trend was observed in urban areas; however, the level of the healthcare providers did not appear to have an effect on the number of cataract surgeries performed.

Purpose: High incidence of osteoporosis has been reported in breast cancer patients due to early menopause triggered by adjuvant treatment and temporary ovarian function suppression. In this study, we sought to determine whether long-term breast cancer survivors had an elevated risk of low bone density compared to the general population. Methods: Long-term breast cancer survivors who had been treated for more than 5 years were selected for this study. Data were obtained from medical records and using a questionnaire from the Korea National Health and Nutrition Examination Survey (KNHANES). An agematched non-cancer control group was selected from the KNHANES records. Incidence of fracture and bone mineral density (BMD) were compared between the two groups. Results: In total, 74 long-term breast cancer survivors and 296 non-cancer controls were evaluated. The incidence of fracture did not differ between the two groups (P=0.130). No differences were detected in lumbar BMD (P=0.051) following adjustment for body mass index, while hip BMD was significantly lower in breast cancer survivors (P=0.028). Chemotherapy and endocrine treatment were not related to low BMD in breast cancer survivors. In more than half of the survivors, the 10-year risk of osteoporotic fracture was less than 1%. Conclusion Long-term breast cancer survivors had low bone density but a comparable risk of fracture compared to non-cancer agematched controls. Further studies on the factors related to low bone density in long-term breast cancer survivors are required.

BACKGROUND AND PURPOSE: To investigate whether appointing a full-time neurointensivist to manage a closed-type neurological intensive care unit (NRICU) improves the quality of critical care and patient outcomes. METHODS: This study included patients admitted to the NRICU at a university hospital in Seoul, Korea. Two time periods were defined according to the presence of a neurointensivist in the preexisting open-type NRICU: the before and after periods. Hospital medical records were queried and compared between these two time periods, as were the biannual satisfaction survey results for the families of patients. RESULTS: Of the 15,210 patients in the neurology department, 2,199 were admitted to the NRICU (n=995 and 1,204 during the before and after periods, respectively; p<0.001). The length of stay was shorter during the after than during the before period in both the NRICU (3 vs. 4 days; p<0.001) and the hospital overall (12.5 vs. 14.0 days; p<0.001). Neurological consultations (2,070 vs. 3,097; p<0.001) and intrahospital transfers from general intensive care units to the NRICU (21 vs. 40; p=0.111) increased from the before to after the period. The mean satisfaction scores of the families of the patients also increased, from 78.3 to 89.7. In a Cox proportional hazards model, appointing a neurointensivist did not result in a statistically significant change in 6-month mortality (hazard ratio, 0.82; 95% confidence interval, 0.652–1.031; p=0.089). CONCLUSIONS: Appointing a full-time neurointensivist to manage a closed-type NRICU had beneficial effects on quality indicators and patient outcomes.
Critical Care Outcomes ; Critical Care ; Humans ; Intensive Care Units ; Korea ; Length of Stay ; Medical Records ; Mortality ; Neurology ; Proportional Hazards Models ; Referral and Consultation ; Seoul