Vitamin D is a fat-soluble vitamin helps to retain calcium and phosphorus but also has shown to affect immune regulation and homeostasis. In humans, vitamin D3 and vitamin D2 and their metabolite has intensively studied in both innate and adaptive immune system that they are important to regulate overwhelmed inflammation. The vitamin D receptor is a nuclear hormone receptor which regulate various downstream target gene expressions as a transcription factor related to metabolism, immune regulation, etc. Vitamin D deficiency is a high-risk factor for inflammatory diseases like autoimmune disease and allergy. In addition, reduced vitamin D seem to correlate with susceptibility to the virus infection such as HIV and COVID-19. In this review, we will summarize up-to-date vitamin D's role in various immune cells, immune regulatory functions during autoimmune, allergic, and infectious diseases. We will also discuss about vitamin D supplement effects in human trial studies for COVID-19.
Junghyun Ryu;Fernanda C. Burch;Emily Mishler;Martha Neuringer;Jon D. Hennebold;Carol Hanna
Journal of Animal Reproduction and Biotechnology
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v.37
no.4
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pp.292-297
/
2022
Direct injection of CRISPR/Cas9 into zygotes enables the production of genetically modified nonhuman primates (NHPs) essential for modeling specific human diseases, such as Usher syndrome, and for developing novel therapeutic strategies. Usher syndrome is a rare genetic disease that causes loss of hearing, retinal degeneration, and problems with balance, and is attributed to a mutation in MYO7A, a gene that encodes an uncommon myosin motor protein expressed in the inner ear and retinal photoreceptors. To produce an Usher syndrome type 1B (USH1B) rhesus macaque model, we disrupted the MYO7A gene in developing zygotes. Identification of appropriately edited MYO7A embryos for knockout embryo transfer requires sequence analysis of material recovered from a trophectoderm (TE) cell biopsy. However, the TE biopsy procedure is labor intensive and could adversely impact embryo development. Recent studies have reported using cell-free DNA (cfDNA) from embryo culture media to detect aneuploid embryos in human in vitro fertilization (IVF) clinics. The cfDNA is released from the embryo during cell division or cell death, suggesting that cfDNA may be a viable resource for sequence analysis. Moreover, cfDNA collection is not invasive to the embryo and does not require special tools or expertise. We hypothesized that selection of appropriate edited embryos could be performed by analyzing cfDNA for MYO7A editing in embryo culture medium, and that this method would be advantageous for the subsequent generation of genetically modified NHPs. The purpose of this experiment is to determine whether cfDNA can be used to identify the target gene mutation of CRISPR/Cas9 injected embryos. In this study, we were able to obtain and utilize cfDNA to confirm the mutagenesis of MYO7A, but the method will require further optimization to obtain better accuracy before it can replace the TE biopsy approach.
Exosomes are a type of extracellular vesicle containing proteins and messenger and microRNAs; they are secreted by all cell types. Once released, exosomes are selectively taken up by other cells adjacent or at a distance, releasing their contents and reprogramming the target cells. Since exosomes are natural vesicles produced by cells as small sizes, it is generally accepted that exosomes have a non-toxic nature and non-immunogenic behaviors. Recently, exosomes have elicited scientific attention as drug delivery vehicles to the central nervous system. The central nervous system has a blood-brain barrier that makes it difficult for drugs to penetrate. Thus, the blood-brain barrier has been a major obstacle to the development of drugs for treating neurodegenerative diseases. However, accumulating evidence suggests that exosomes can cross the blood-brain barrier primarily through transcytosis. Consequently, exosomes are expected to become a new delivery vehicle that can cross the blood-brain barrier and deliver drugs into the brain parenchyma. In addition, since different types of exosomes are secreted depending on the cell type and disease state, exosomes can also be utilized as biomarkers for the diagnosis of diseases in the central nervous system. In this review, we summarized recent research trends on exosomes, including clinical trials as biomarkers and treatment options for diseases in the central nervous system.
Leucine-rich repeat kinase 2 (LRRK2) is known to play a crucial role in the pathophysiology of neurodegenerative disorders such as Parkinson's disease. LRRK2 is predominantly expressed in the lung as well as the brain. However, it is unclear whether LRRK2 expression correlates with the pathogenesis of lung squamous cell carcinoma (LUSC). This study analyzes the prognostic significance of LRRK2 in LUSC using the Kaplan-Meier plotter tool. High expression of LRRK2 is known to be associated with a bad prognosis in patients with LUSC. Patients with high LRRK2 expression, tumor mutational burden, high neoantigen load, and even gender correlation reportedly have the worse survival rates. In the gene expression profiling interactive analysis (GEPIA) database, the severity of pathogenesis in LUSC with high LRRK2 expression positively corresponds to a high expression of anti-inflammatory cytokines but not inflammatory cytokines. Similarly, the increased expression of interleukin (IL)10-related genes was shown to be significantly linked in LRRK2-high LUSC patients having a poor prognosis. Moreover, the tumor immune estimation resource (TIMER) database suggests that macrophages are one of the cellular sources of IL10 in LRRK2-high LUSC patients. Collectively, our results demonstrate that the postulated LRRK2-IL10 axis is a potential therapeutic target and prognostic biomarker for LUSC.
Li Zhang;Dong Li;Min Lu;Zechi Wu;Chaotian Liu;Yingying Shi;Mengyu Zhang;Zhangjie Nan;Weixiang Wang
The Plant Pathology Journal
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v.39
no.4
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pp.361-373
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2023
In plant-pathogen interactions, Magnaporthe oryzae causes blast disease on more than 50 species of 14 monocot plants, including important crops such as rice, millet, and most 15 recently wheat. M. oryzae is a model fungus for studying plant-microbe interaction, and the main source for fungal pathogenesis in the field. Here we report that MoJMJD6 is required for conidium germination and appressorium formation in M. oryzae. We obtained MoJMJD6 mutants (ΔMojmjd6) using a target gene replacement strategy. The MoJMD6 deletion mutants were delayed for conidium germination, glycogen, and lipid droplets utilization and consequently had decreased virulence. In the ΔMojmjd6 null mutants, global histone methyltransferase modifications (H3K4me3, H3K9me3, H3K27me3, and H3K36me2/3) of the genome were unaffected. Taken together, our results indicated that MoJMJD6 function as a nuclear protein which plays an important role in conidium germination and appressorium formation in the M. oryzae. Our work provides insights into MoJMJD6-mediated regulation in the early stage of pathogenesis in plant fungi.
Jaeim Lee;Jong-Hwan Kim;Hoang Bao Khanh Chu;Seong-Taek Oh;Sung-Bum Kang;Sejoon Lee;Duck-Woo Kim;Heung-Kwon Oh;Ji-Hwan Park;Jisu Kim;Jisun Kang;Jin-Young Lee;Sheehyun Cho;Hyeran Shim;Hong Seok Lee;Seon-Young Kim;Young-Joon Kim;Jin Ok Yang;Kil-yong Lee
Molecules and Cells
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v.47
no.3
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pp.100033.1-100033.13
/
2024
Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.
Se-hun Moon;Jung-ho Jo;Seung-kwan Choi;Yun-hee Han;Hyeon-jun Woo;Byeong-hyeon Jeon;Won-bae Ha;Jung-han Lee
The Journal of Internal Korean Medicine
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v.44
no.6
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pp.1212-1242
/
2023
Objectives: This study aims to explore the current usage status of orally administered Korean herbal medicine in randomized controlled trials (RCTs) published in the Journal of Korean Medicine and member journals using the CONSORT-Chinese Herbal Medicine Formulas 2017 (CONSORT-CHM 2017) checklist. Methods: We searched the OASIS, RISS, and KMBASE archives as well as the websites of the Journal of Korean Medicine and 45 member journals to identify RCTs that used herbal interventions. Two independent researchers searched and categorized the RCTs and performed a quantitative evaluation by journal, study design, and target disease, as well as qualitative evaluation of the literature using CONSORT-CHM 2017. Results: After the search, 66 articles were selected. The quantitative evaluation resulted in 13 articles (19.6%) that were published in the Journal of Korean Medicine and 12 articles (18.1%) in the Journal of Internal Korean Medicine. In terms of study design, 62 articles (93.9%) were parallel, 4 articles (6%) were crossover, and 2-arm parallel study designs were the most common in 45 articles (68.2%). In terms of the study participants, physiological characteristics and mechanisms in healthy individuals were the most common in 21 studies (31.8%) and obesity in 9 studies (13.6%). In terms of assessing completeness in the CONSORT-CHM 2017 items, 29 articles were rated high, 31 were rated moderate, and 6 were rated low. Items 4a, 6a, and 7a had low reporting rates (≤ 30%), while items 2a, 2b, and 12a were completely reported in all studies. Conclusion: Future RCTs using orally administered Korean herbal medicine need to be reported completely, and the CONSORT-CHM 2017 checklist can be a helpful tool for this purpose.
As the use of environmentally friendly and non-disease natural pigments grows, various methods for extracting natural pigments have been studied. The natural color was extracted from parsley, a vegetable ingredient containing natural dyes. Target color codes of green series of natural dyes extracted as variables #50932C (L = 55.0, a = -40.0, b = 46.0) were set with the pH and temperature of extracted natural color coordinates (of the extracted), and the quantitative intensities of natural dyes were analyzed. During the colorimetric analysis predicted by the reaction surface analysis method, a color coordinate analysis was conducted under the optimal conditions of pH 8.0 and extraction temperature of $60.9^{\circ}C$. Under these conditions, predicted figures of L, a, and b were 55.0, -36.3, and 36.8, respectively, while actual experimental ones confirmed were 69.0, -35.9, and 31.4, respectively. In these results, the theory accuracy and actual error rate were confirmed to be 73.0 and 13.8%, respectively. The theoretical optimization condition of the color difference (${\Delta}E$) was at the pH of 9.2 and extraction temperature of $55.2^{\circ}C$. Under these conditions the predicted ${\Delta}E$ figure was 12.4 while the experimental one was 13.0. The difference in color analysis showed 97.5% of the theoretical accuracy and 4.5% of the actual error rate. However, the combination of color coordinates did not represent a desired target color, but rather close to the targeted color by means of an arithmetic mean. Therefore, it can be said that when the reaction surface analysis method was applied to the natural dye extraction process, the use of color coordinates as a response value can be a better method for optimizing the dye extraction process.
Park, Ju-Kyeong;Lee, Seung-Hun;Cha, Seok-Yong;Kim, Yang-Su;Lee, Sun-Young
Journal of the Korean Society of Radiology
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v.6
no.2
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pp.151-157
/
2012
General treatment for cholangiocarcinoma is complete surgical resection. However recurrence is common in those patients. In most of cases the purpose of the treatment for patients with recurrent is palliative. Therefore we adopt intraluminal catheter to treat a recurrent patient with high-dose-rate intraluminal brachytherapy. This study aims to evaluate the treatment procedure and set-up reproducibility of intraluminal brachytherapy in the recurrent patient. Study patient was diagnosed at rcT1N0M0 and undergone intraluminal brachytherapy after Arrow Sheath insertion. 3 Gy was delivered in every fraction with a total dose of 30 Gy. We planned dose normalization at distal, proximal and central axis point of narrowed bile duct far from 1 cm. To evaluate set-up reproducibility, we measured distance between distal, proximal treatment target volume point and anterior surface of the thoracic vertebral body respectively for five times before every treatment with dummy seed insertion. Mean distance between distal, proximal treatment target volume point and anterior surface of 10th and 11th thoracic vertebral bodies is 0.5 cm, 6.1 cm and standard deviation is 0.06, 0.08 respectively. In addition, set-up reproducibility was maintained significantly. The patient has been alive with no evidence of disease recurrence for more than a year and has not yet reported severe complications. In conclusion, high-dose-rate intraluminal brachytherapy for unresectable recurrence of cholangiocarcinoma maintains high set-up reproducibility without severe side effects.
Kim, Ho-Joong;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Kim, Keun-Youl;Han, Yong-Chol
Tuberculosis and Respiratory Diseases
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v.40
no.5
/
pp.509-518
/
1993
Background: By amplifying small amount of DNA, polymerase chain reaction (PCR) can be used for the detection of very small amount of microbial agent, and may be especially useful in certain cases which are difficult to be diagnosed microbiologically or serologically. Tuberculous pleurisy is a disease that can be diagnosed in only 70% of cases by conventional diagnostic tools, and PCR would be a very rapid, easy, and sensitive diagnostic method. Method: The specificity and sensitivity of PCR to detect Mycobacterium tuberculosis DNA were evaluated using various strains of Mycobacteria. To evaluate the diagnostic usefulness of PCR in tuberculous pleurisy, we used PCR to detect Mycobacterium tuberculosis DNA in pleural fluid. The amplification target was 123 base pair DNA, a part of IS6110 fragment, 10~16 copies of which are known to exist per genome. The diagnostic yield of PCR was compared with conventional methods, including pleural fluid adenosine deaminase (ADA) activity. Also, the significance of PCR in undiagnosed pleural effusion was evaluated prospectively with antituberculosis treatment. Results: 1) Using cultured Mycobacterium tuberculosis and other strains, PCR could detect upto 1 fg DNA and specific for only Mycobacterium tuberculosis and Mycobacterium bovis. 2) Using pleural effusions of proven tuberculosis cases, the sensitivity of PCR was 80.0% (16/20), and the specificity 95.0% (19/20). 3) Among 13 undiagnosed, but suspected tuberculous effusion, the positive rate was 60% in 10 improved cases after antituberculosis medications, and 0% in 3 cases of proven malignancy later. 4) Adenosine deaminase level of proven and clinically diagnosed tuberculous pleurisy patients was significantly higher than that of excluded patients, and correlated well with PCR results. Conclusion: We can conclude that PCR detection of Mycobacterium tuberculosis in pleural effusion has acceptable sensitivity and specificity, and could be an additional diagnostic tool for the diagnosis of tuberculous pleurisy.
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