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1.
Immune Network ; : e3-2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-1040794

ABSTRACT

Microvilli are outer membrane organelles that contain cross-linked filamentous actin.Unlike well-characterized epithelial microvilli, T-cell microvilli are dynamic similar to those of filopodia, which grow and shrink intermittently via the alternate actin-assembly and -disassembly. T-cell microvilli are specialized for sensing Ags on the surface of Ag-presenting cells (APCs). Thus, these finger-shaped microprotrusions contain many signaling-related proteins and can serve as a signaling platforms that induce intracellular signals. However, they are not limited to sensing external information but can provide sites for parts of the cell-body to tear away from the cell. Cells are known to produce many types of extracellular vesicles (EVs), such as exosomes, microvesicles, and membrane particles. T cells also produce EVs, but little is known about under what conditions T cells generate EVs and which types of EVs are released. We discovered that T cells produce few exosomes but release large amounsts of microvilli-derived particles during physical interaction with APCs. Although much is unanswered as to why T cells use the same organelles to sense Ags or to produce EVs, these events can significantly affect T cell fate, including clonal expansion and death. Since TCRs are localized at microvilli tips, this membrane event also raises a new question regarding long-standing paradigm in T cell biology; i.e., surface TCR downmodulation following T cell activation. Since T-cell microvilli particles carry T-cell message to their cognate partner, these particles are termed T-cell immunological synaptosomes (TISs). We discuss the potential physiological role of TISs and their application to immunotherapies.

2.
Immune Network ; : e29-2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-1040796

ABSTRACT

Cholesterol (CL) is required for various biomolecular production processes, including those of cell membrane components. Therefore, to meet these needs, CL is converted into various derivatives. Among these derivatives is cholesterol sulfate (CS), a naturally produced CL derivative by the sulfotransferase family 2B1 (SULT2B1), which is widely present in human plasma. CS is involved in cell membrane stabilization, blood clotting, keratinocyte differentiation, and TCR nanocluster deformation. This study shows that treatment of T cells with CS resulted in the decreased surface expression of some surface T-cell proteins and reduced IL-2 release. Furthermore, T cells treated with CS significantly reduced lipid raft contents and membrane CLs. Surprisingly, using the electron microscope, we also observed that CS led to the disruption of T-cell microvilli, releasing small microvilli particles containing TCRs and other microvillar proteins. However, in vivo, T cells with CS showed aberrant migration to high endothelial venules and limited infiltrating splenic T-cell zones compared with the untreated T cells. Additionally, we observed significant alleviation of atopic dermatitis in mice injected with CS in the animal model. Based on these results, we conclude that CS is an immunosuppressive natural lipid that impairs TCR signaling by disrupting microvillar function in T cells, suggesting its usefulness as a therapeutic agent for alleviating T-cellmediated hypersensitivity and a potential target for treating autoimmune diseases.

3.
Article in English | WPRIM (Western Pacific) | ID: wpr-1041468

ABSTRACT

Transmembrane protein 115 (TMEM115) is a membrane protein; considering the potential of membrane proteins as biomarkers for various pathological conditions, we aimed to examine the value of TMEM115 as a potential biomarker for improving the prognosis and treatment of liver hepatocellular carcinoma (LIHC) in this study. Online databases including the Tumor Immune Estimation Resource, UALCAN, Gene Expression Profiling Interactive Analysis version 2, OSlihc, and human Protein Atlas were used. The analysis suggested that TMEM115 expression in LIHC was higher compared to normal tissues; further, TMEM115 expression was confirmed to be related with poor prognosis in LIHC. Higher protein expression levels of TMEM115 were observed in LIHC tissues than in normal tissues. Tumor infiltration by immune cells was confirmed to be correlated with the expression of TMEM115. High TMEM115 expression and immune cell infiltration were further related to poor prognosis in LIHC. We also confirmed a correlation between TMEM115 and TP53 mutations. In conclusion, we confirmed that TMEM115 expression is correlated with tumor-infiltrating immune cells and poor prognosis in LIHC and that TMEM115 shows potential as a prognostic biomarker in LIHC.

4.
Article in English | WPRIM (Western Pacific) | ID: wpr-1041813

ABSTRACT

Objectives@#The prognostic significance of CDC42 effector protein 2 (CDC42EP2) and its association with tumor-infiltrating immune cells (TIICs) have not been explored in liver hepatocellular carcinoma (LIHC). This study aims to assess the potential prognostic value of CDC42EP2 by conducting a comprehensive analysis of online databases pertaining to LIHC. @*Methods@#We evaluated the potential of CDC42EP2 as a prognostic biomarker by utilizing online databases such as TIMER, GEPIA2, KM, OSlihc, HPA, and LinkedOmics. @*Results@#In LIHC, we observed that the mRNA and protein expression of CDC42EP2 were upregulated compared to normal tissues. Upregulated CDC42EP2 expression was associated with a worse prognosis based on the clinicopathological characteristics of patients with LIHC. Furthermore, CDC42EP2 was positively associated with TIICs. In the co-expression and functional enrichment analyses of CDC42EP2, 11,416 genes showed positive associations with CDC42EP2 while 8,008 genes showed negative associations. CDC42EP2-related co-expression genes were involved in protein localization to the endoplasmic reticulum, translational initiation, and RNA catabolic processes in gene set enrichment analysis-Gene Ontology (GSEA-GO), and regulated the ribosome, spliceosome, and primary immune deficiency in the GSEA-Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. In a survival map, 23 and 17 genes that exhibited positive associations with CDC42EP2 showed a significant hazard ratio (HR) for overall survival and disease-free survival, respectively. @*Conclusion@#Our findings demonstrated that CDC42EP2 is a novel prognostic biomarker and a potential tumor immune therapeutic target in patients with LIHC.

5.
Annals of Dermatology ; : 138-146, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-874102

ABSTRACT

Background@#The aryl hydrocarbon receptor (AHR) and autophagy are both important to maintain skin homeostasis.However, they are also involved in skin disorders. So far, their roles in psoriasis pathogenesis are unknown. @*Objective@#We studied the immunohistochemical and gene expression of AHR, CYP1A1, and microtubule-associated protein light chain 3 (LC3) in lesional skin of psoriasis patients to determine correlations among them. @*Methods@#We included 24psoriasis patients and ten healthy volunteers. Skin biopsies were collected. AHR, CYP1A1, and LC3 protein expression was examined by immunohistochemistry, immunofluorescence, and western blotting. AHR, CYP1A1, LC3, ATG5, BECN1 and Nrf2 mRNA levels were measured by quantitative polymerase chain reaction. @*Results@#AHR and CYP1A1 protein expression were higher in psoriasis lesional skin than in normal skin. LC3 protein expression was lower in psoriasis lesions than in normal controls. AHR and CYP1A1 protein expression in psoriasis lesions showed significant positive correlations with mean epidermal thickness and inflammatory cell density. Significant negative correlations were noted between LC3 protein expression in psoriasis lesions and the mean epidermal thickness or inflammatory cell density. A significant negative correlation was found between AHR and LC3 expression in psoriatic skin. AHR, CYP1A1 and Nrf2 mRNA expression were upregulated while LC3, ATG5, and BECN1 mRNA were down-regulated, in psoriatic lesional skin compared with normal controls. @*Conclusion@#AHR and autophagy could play a role in psoriasis pathogenesis by modifying epidermal hyperproliferation and inflammation. AHR and autophagy regulation are potential therapeutic targets in chronic inflammatory skin diseases.

6.
Article in English | WPRIM (Western Pacific) | ID: wpr-874149

ABSTRACT

Phospholipase C beta 2 (PLC-β2) regulates various essential functions in cell signaling, differentiation, growth, and mobility. We investigated the clinical implications of PLC-β2 protein expression in newly diagnosed normal karyotype acute myeloid leukemia (NKAML). The PLC-β2 expression status in bone marrow tissues obtained from 101 patients with NK-AML was determined using semiquantitative immunohistochemistry (IHC). IHC results were compared with those for known prognostic markers. Using a cutoff score for positivity of 7.0, the PLC-β2 overexpression group showed superior overall survival (OS) (72.6% vs. 26.5%; P = 0.016) and low hazard ratio (HR) (0.453; P = 0.019) compared with the PLC-β2 low-expression group. The PLC-β2 overexpression group showed no significant gain in event-free survival (50.6% vs. 43.0%, P =0.465) and HR (0.735; P =0.464).Among the known prognostic markers, only FLT3-ITD positivity was associated with a significantly low OS and high HR. In conclusion, PLC-β2 overexpression was associated with favorable OS in NK-AML patients. Our results suggest that PLC-β2 expression assessment using IHC allows prognosis prediction in NK-AML.

7.
Article in English | WPRIM (Western Pacific) | ID: wpr-918649

ABSTRACT

Objectives@#The aims of this study were to investigate the expression of Yes-associated protein 1 (YAP1), its prognostic significance, and the correlation between YAP1 and telomerase in various cancers. @*Methods@#The Gene Expression Profiling Interactive Analysis database was used to analyze RNA sequencing data and the survival rate of patients with various cancers in The Cancer Genome Atlas (TCGA) database. PrognoScan was used to analyze the prognostic value of YAP1 expression in various cancers. Tumor Immune Estimation Resource was used to determine the correlation between YAP1 expression and telomerase in various cancer types based on TCGA data. @*Results@#The analysis suggested that YAP1 was differentially expressed between tissues of various cancers and non-tumor tissues. High YAP1 expression was also related to a poor prognosis in adrenocortical carcinoma, bladder urothelial carcinoma, and pancreatic adenocarcinoma. Moreover, YAP1 expression was correlated with the expression of telomerase reverse transcriptase and telomerase RNA component in various cancer types. @*Conclusion@#These results suggest that YAP1 is a potential biomarker with prognostic significance and relevance for oncogene research in various cancer types. The correlation between the expression of YAP1 and telomere-associated genes will help to understand their cancer-promoting mechanisms and interactions.

8.
Laboratory Medicine Online ; : 214-220, 2020.
Article | WPRIM (Western Pacific) | ID: wpr-836922

ABSTRACT

Background@#Prohibitin (PHB) regulates intracellular signal pathways, transcription, and cell cycles. Aberrant expression of the PHB gene is known to be related totumorigenesis, tumor progression, and chronic metabolic and inflammatory diseases. The present study aimed to develop a one-step quantitative reverse transcription PCR (RT-qPCR) kit for quantifying PHB mRNA levels and evaluate its performance in the laboratory. @*Methods@#TaqMan chemistry was used to develop the one-step PHB1 and PHB2 RT-qPCR kit. Normal peripheral blood cells from healthy individuals (N=20) and leukemia cells from patients initially diagnosed with acute myeloid leukemia (AML, N=20), chronic myeloid leukemia (CML, N=13), and acute lymphoid leukemia (ALL, N=7) were enrolled to evaluate the laboratory performance of the kit using commercially available total human RNA controls. @*Results@#The intra-assay and inter-assay precision of the kit developed in this study was less than 2%. The distribution of PHB1 mRNA expression of AML, CML, and ALL was 0.898-0.993 (median: 0.936), 0.817-0.976 (0.918), and 0.844-1.074 (0.973), respectively. The distribution of PHB2 mRNA expression of AML, CML, and ALL was 0.957-1.024 (median: 0.985), 0.988-1.047 (1.002), and 0.937-1.059 (1.004), respectively. The sensitivity, specificity, positive and negative predictive value, and test effectiveness of the developed PHB1 and PHB2 kit were greater than 50% for each parameter. @*Conclusions@#Our developed kit would be useful for diagnosing leukemia as well as detecting residual disease. Additionally, this kit could be used for monitoring and conducting molecular pathophysiological studies of obesity, metabolic, and inflammatory diseases.

10.
Blood Research ; : 225-245, 2020.
Article in English | WPRIM (Western Pacific) | ID: wpr-897339

ABSTRACT

Background@#Chromosomal analysis is essential for the diagnosis and risk stratification of all leukemia patients. Not surprisingly, racial differences in chromosomal aberrations (CA) in hematological malignancies could be found, and CA incidence in leukemia might change over time, possibly due to environmental and lifestyle changes. Thus, we compared the frequency and range of CA in patients with acute leukemia (AL) during two time periods (2006‒2009 vs. 2010‒2015) and compared them with other prior studies. @*Methods@#We enrolled 717 patients with AL during a six-year period (2010‒2015). We compared the results to those of our earlier study (2006‒2009) [1]. Conventional cytogenetics, a multiplex reverse transcriptase (RT)-PCR system, and fluorescence in situ hybridization were employed to assess bone marrow specimens or peripheral blood at the diagnostic stage in AL patients to detect CA. @*Results@#The incidence of CA changed in the leukemia subgroups during the two time periods.Notably, the most frequent CA of childhood acute myeloid leukemia (AML) was PML/RARA, and was followed by RUNX1/RUNX1T1 in the current study. In contrast, the most common CA was RUNX1/RUNX1T1 in a previous study [1] and was followed by PML/RARA. In this study, the most frequent CA of the mixed phenotype AL was BCR/ABL1, which was followed by KMT2A/MLLT3. In a previous report, [1] the most frequent CA was BCR/ABL1, which was followed by KMT2A/ELL. @*Conclusion@#The distribution of CA in Korean AL patients changed over time in a single institute. This change might be due to environmental and lifestyle changes.

11.
Annals of Dermatology ; : 319-326, 2020.
Article | WPRIM (Western Pacific) | ID: wpr-831409

ABSTRACT

Background@#Several epidemiological studies have shownthat the atopic tendency increases in the obese population. @*Objective@#The aim of this study was to confirm the effect ofweight reduction on improvement of atopic dermatitis (AD)symptoms and to investigate the relationship between AD severityand the level of serum adipokines. @*Methods@#Forty subjectswho were AD outpatients were recruited for this study.Obese patients were divided into a weight maintenancegroup and weight reduction group. During the study period,patient information was collected that included measuredbody mass index (BMI), Eczema Area and Severity Index(EASI), and visual analogue scale for pruritus. Adiponectin,leptin, eosinophil count, and total immunoglobulin E werealso tested. @*Results@#In the weight reduction group, there wasa significant improvement in the EASI score, however, no significantimprovement was determined in the weight maintenancegroup. BMI and EASI showed positive correlation.The adiponectin level was lower in AD patients compared tohealthy controls, and it was significantly lower in obese patients compared with normal weight patients. Serum levels ofleptin were significantly different among control, obese patientgroup, and normal weight patient group. There was nostatistically significant relationship between serum adipokinelevel and EASI. @*Conclusion@#In our study, weight reductionwas associated with significant improvement of ADsymptoms. Related adipokine levels were significantly differentamong the control, normal weight AD patient group, andobese AD patient group.

12.
Blood Research ; : 225-245, 2020.
Article in English | WPRIM (Western Pacific) | ID: wpr-889635

ABSTRACT

Background@#Chromosomal analysis is essential for the diagnosis and risk stratification of all leukemia patients. Not surprisingly, racial differences in chromosomal aberrations (CA) in hematological malignancies could be found, and CA incidence in leukemia might change over time, possibly due to environmental and lifestyle changes. Thus, we compared the frequency and range of CA in patients with acute leukemia (AL) during two time periods (2006‒2009 vs. 2010‒2015) and compared them with other prior studies. @*Methods@#We enrolled 717 patients with AL during a six-year period (2010‒2015). We compared the results to those of our earlier study (2006‒2009) [1]. Conventional cytogenetics, a multiplex reverse transcriptase (RT)-PCR system, and fluorescence in situ hybridization were employed to assess bone marrow specimens or peripheral blood at the diagnostic stage in AL patients to detect CA. @*Results@#The incidence of CA changed in the leukemia subgroups during the two time periods.Notably, the most frequent CA of childhood acute myeloid leukemia (AML) was PML/RARA, and was followed by RUNX1/RUNX1T1 in the current study. In contrast, the most common CA was RUNX1/RUNX1T1 in a previous study [1] and was followed by PML/RARA. In this study, the most frequent CA of the mixed phenotype AL was BCR/ABL1, which was followed by KMT2A/MLLT3. In a previous report, [1] the most frequent CA was BCR/ABL1, which was followed by KMT2A/ELL. @*Conclusion@#The distribution of CA in Korean AL patients changed over time in a single institute. This change might be due to environmental and lifestyle changes.

13.
Laboratory Medicine Online ; : 169-174, 2020.
Article in English | WPRIM (Western Pacific) | ID: wpr-1045689

ABSTRACT

Chromosome 4q deletion syndrome is a rare disease caused by partial deletion of the long arm of chromosome 4. Phenotypic severity and expressivity vary among patients with chromosome 4q deletions, depending on the size and region of the deletion of the affected chromosome. Although there have been many reports of proximal 4q deletion cases, very few have been confirmed by high-resolution array comparative genomic hybridization (aCGH). In the current study, we presented a new case of 4q proximal deletion, with detailed genetic and clinical characteristics, and compared these characteristics to those of six previous cases with available aCGH data. According to our review, several genes known to be associated with specific phenotypes of 4q12q21.1 deletion cannot sufficiently explain the variable phenotypes observed among the cases. These phenotypes include mental retardation, microcephaly, ocular anomalies, dental anomaly, and piebaldism. Consequently, we recommend further detailed investigations into the genes associated with 4q12q21.1 deletion to assist in identifying genotype-phenotype associations more clearly.

14.
Blood Research ; : 253-261, 2019.
Article in English | WPRIM (Western Pacific) | ID: wpr-785541

ABSTRACT

BACKGROUND: Fluoranthene (FR) is a common environmental pollutant that exists in a complex mixture with other polycyclic aromatic hydrocarbons (PAHs). We identified biomarkers for monitoring FR exposure and investigated the rescue effect of FR-induced cellular toxicity via aryl hydrocarbon receptor (AHR) antagonist activity in bone marrow derived mesenchymal stem cells (BM-MSCs).METHODS: Morphological changes, viability, and rescue effects of an AHR antagonist (CH223191) were examined in BM-MSCs after exposure to FR. Cytotoxic effects were assayed using the tetrazolium-based colorimetric assay. Apoptosis was measured by annexin V and propidium iodide dye-based flowcytometry assay, mitochondrial membrane potential assay, and nuclear DNA fragmentation assay. Molecular signaling pathways of apoptosis and autophagy were investigated using immunoblotting. Proteomics were performed in order to reveal the spectra of cellular damage and identify biomarkers for FR exposure.RESULTS: Exposing BM-MSCs to FR (IC₅₀=50 µM) induced cell death and morphological changes, while the AHR antagonist showed rescue effects. Autophagy was activated and mitochondrial membrane potential was decreased. Proteomic analysis identified 48 deregulated proteins (26 upregulated and 22 downregulated). Among them, annexin A6, pyruvate kinase, UDP-glucose dehydrogenase, and phospholipase A2 could be potential biomarkers for FR exposure.CONCLUSION: The exposure of BM-MSCs to FR induced remarkable alterations in cellular biology and the proteome, allowing for identification of novel biomarkers for FR exposure. Furthermore, AHR antagonists might be able to prevent cellular damage due to FR exposure.


Subject(s)
Annexin A5 , Annexin A6 , Apoptosis , Autophagy , Biomarkers , Bone Marrow , Cell Death , DNA Fragmentation , Immunoblotting , Membrane Potential, Mitochondrial , Mesenchymal Stem Cells , Oxidoreductases , Phospholipases A2 , Polycyclic Aromatic Hydrocarbons , Propidium , Proteome , Proteomics , Pyruvate Kinase , Receptors, Aryl Hydrocarbon
15.
Article in English | WPRIM (Western Pacific) | ID: wpr-764238

ABSTRACT

Classical swine fever (CSF), previously known as hog cholera, remains one of the most important swine-related contagious diseases worldwide. In order to eradicate classical swine fever virus (CSFV), it is commonly used in LOM-850 strain as a live attenuated CSF vaccine. However, there are symptoms of vaccination, such as the depression of feed intake, and difficulty of differentiation between infected and vaccinated hosts is impossible based on the antibodies induced. Nicotiana benthamiana were considered as an alternative to the production of recombinant vaccines on account of higher yields and levels of soluble protein than other models and crops in protein recombinant products. This study was conducted to evaluate histopathological validation of the plant-produced E2 fusion protein (ppE2) in piglets. The piglets were challenged by an injection of YC11WB strain in 7 days, 11 days and 14 days after one shot of the vaccination. The histopathological examination indicated that ppE2 can protect against lethal CSFV challenge at least 11 days of vaccination in piglets. These data suggest that the ppE2 can be an effective vaccine against CSFV in piglets.


Subject(s)
Animals , Antibodies , Classical Swine Fever Virus , Classical Swine Fever , Depression , Swine , Nicotiana , Vaccination , Vaccines, Synthetic
17.
Article in English | WPRIM (Western Pacific) | ID: wpr-740300

ABSTRACT

The hepatitis C virus (HCV) is a globally prevalent human pathogen that causes persistent liver infections in most infected individuals. Several studies reported that HCV particles are enriched in apolipoprotein E (apoE) and that apoE is required for HCV infectivity and production. However, the relationship between apoE gene polymorphisms and HCV genotypes in patients with HCV is less well understood. The aim of this study was to investigate the association between apoE gene polymorphism and HCV genotypes in patients. The HCV genotypes were identified among the 124 patients infected with HCV, and the genetic characteristics of the HCV genotype were analyzed. In addition, the results of the clinical laboratory test were comparatively analyzed according to the classified genotypes. Both HCV 1b (n=80) and 2a (n=42) patients had higher AFP, AST, ALT, ALP, γ-GTP, apoB, and apoE values compared with the normal control group. In particular, apoB and apoE levels were statistically significantly higher in the HCV 2a patients (P<0.05) and apoE levels were significantly higher in the HCV 1b patients (P<0.000). According to the results the patients with HCV genotype 1b showed higher values of liver damage related indicators and apoB expression than the patients with HCV genotype 2a. The fat related indicators and apoE expression were not different between the two major HCV genotypes (2a and 1b). We anticipate that the apoE ε3 allele is the most common type in HCV genotype 1b (89.2%) and 2a (91.7%). As a result of apoE genotyping, we confirmed an association with HCV infection and the apoE ε3 allele. However, the ratios of the apoE ε3 allele among the patients with genotype 1b and 2a were similar to each other.


Subject(s)
Humans , Alleles , Apolipoproteins B , Apolipoproteins E , Apolipoproteins , Genotype , Hepacivirus , Hepatitis C , Hepatitis , Liver
18.
Blood Research ; : 240-249, 2018.
Article in English | WPRIM (Western Pacific) | ID: wpr-716606

ABSTRACT

BACKGROUND: Mitochondrial DNA (mtDNA) mutations may regulate the progression and chemosensitivity of leukemia. Few studies regarding mitochondrial aberrations and haplogroups in acute myeloid leukemia (AML) and their clinical impacts have been reported. Therefore, we focused on the mtDNA length heteroplasmies minisatellite instability (MSI), copy number alterations, and distribution of mitochondrial haplogroups in Korean patients with AML. METHODS: This study investigated 74 adult patients with AML and 70 controls to evaluate mtDNA sequence alterations, MSI, mtDNA copy number, haplogroups, and their clinical implications. The hypervariable (HV) control regions (HV1 and HV2), tRNA(leu1)gene, and cytochrome b gene of mtDNA were analyzed. Two mtDNA minisatellite markers, 16189 poly-C (¹⁶¹⁸⁴CCCCCTCCCC¹⁶¹⁹³, 5CT4C) and 303 poly-C (³⁰³CCCCCCCTCCCCC³¹⁵, 7CT5C), were used to examine the mtDNA MSI. RESULTS: In AML, most mtDNA sequence variants were single nucleotide substitutions, but there were no significant differences compared to those in controls. The number of mtMSI patterns increased in AML. The mean mtDNA copy number of AML patients increased approximately 9-fold compared to that of controls (P < 0.0001). Haplogroup D4 was found in AML with a higher frequency compared to that in controls (31.0% vs. 15.7%, P=0.046). None of the aforementioned factors showed significant impacts on the outcomes. CONCLUSION: AML cells disclosed more heterogeneous patterns with the mtMSI markers and had increased mtDNA copy numbers. These findings implicate mitochondrial genome instability in primary AML cells. Therefore, mtDNA haplogroup D4 might be associated with AML risk among Koreans.


Subject(s)
Adult , Humans , Cytochromes b , DNA, Mitochondrial , Genome, Mitochondrial , Leukemia , Leukemia, Myeloid, Acute , Minisatellite Repeats
19.
Article in English | WPRIM (Western Pacific) | ID: wpr-717062

ABSTRACT

Mitochondria are the powerhouses of the cell as well as the primary site of hematopoiesis, which also occurs in the cytoplasm. Hematopoietic stem cells (HSCs) are characterized by a very high turnover rate, and are thus considered to be relatively free from the age-related insults generated by mitochondria. However, HSCs are also subject to these age-related insults, including the incidence of myeloid proliferative diseases, marrow failure, hematopoietic neoplasms, and deterioration of the adaptive human immune system. Recently, NAD⁺ dietary supplements, known as niacin or vitamin B₃, including tryptophan, nicotinic acid, nicotinamide, and the newly identified NAD⁺ precursor nicotinamide riboside, have been shown to play a role in restoring adult stem cell function through the amelioration of mitochondrial dysfunction. This insight motivated a study that focused on reversing aging-related cellular dysfunction in adult mouse muscle stem cells by supplementing their diet with nicotinamide riboside. The remedial effect of nicotinamide riboside enhanced mitochondrial function in these muscle stem cells in a SIRT1-dependent manner, affecting cellular respiration, membrane potential, and production of ATP. Accordingly, numerous studies have demonstrated that sirtuins, under nuclear/mitochondrial control, have age-specific effects in determining HSC phenotypes. Based on the evidence accumulated thus far, we propose a clinical intervention for the restoration of aged HSC function by improving mitochondrial function through NAD⁺ precursor supplementation.


Subject(s)
Adult , Animals , Humans , Mice , Adenosine Triphosphate , Adult Stem Cells , Aging , Bone Marrow , Cell Respiration , Cytoplasm , Diet , Dietary Supplements , Hematologic Neoplasms , Hematopoiesis , Hematopoietic Stem Cells , Immune System , Incidence , Membrane Potentials , Mitochondria , Niacin , Niacinamide , Phenotype , Sirtuins , Stem Cells , Tryptophan , Vitamins
20.
Article in Korean | WPRIM (Western Pacific) | ID: wpr-760480

ABSTRACT

BACKGROUND: Whole blood viscosity (WBV) refers to the internal resistance that occurs when blood flows through blood vessels. WBV is known to be related to many diseases including cardiovascular and neurovascular diseases. We have investigated the analytical performance and established reference intervals for a newly developed microfluidic viscometer, Viscore-300 (NanoBiz, Korea), used for the measurement of WBV. METHODS: We performed a precision test of 240 measurements over 20 days using three control materials. For evaluation of repeatability, a total of 60 WBV measurements were made in 3 whole blood samples 20 times a day. A total of 100 whole blood samples were used to evaluate the accuracy of the Viscore-300 in comparison to a rotating viscometer, DV3T (Brookfield, USA), in accordance with the the Clinical and Laboratory Standards Institute's guidelines. To establish the reference intervals, 122 healthy individuals were enrolled in this study. RESULTS: The precision and repeatability results showed that the CV was less than 5% for three samples and two shear rates. In the accuracy test, the mean differences between two viscometers were 0.09 cP (0.9%) and −0.07 cP (−1.4%) at shear rates of 10 s−1 and 300 s−1, respectively. The reference intervals of WBV for men were 6.88–13.52 cP at 10 s−1 and 4.32–6.43 cP at 300 s−1; those of women were 5.74–13.29 cP at 10 s−1 and 3.60–6.12 cP at 300 s−1. CONCLUSIONS: Viscore-300 showed excellent precision and accuracy and it might be a good instrument for reporting WBV quickly and accurately.


Subject(s)
Female , Humans , Male , Blood Vessels , Blood Viscosity , Microfluidics
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