• Molecules and Cells
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• 제46권10호
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• pp.611-626
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• 2023

Acute myeloid leukemia (AML) is a heterogeneous disease caused by distinctive mutations in individual patients; therefore, each patient may display different cell-type compositions. Although most patients with AML achieve complete remission (CR) through intensive chemotherapy, the likelihood of relapse remains high. Several studies have attempted to characterize the genetic and cellular heterogeneity of AML; however, our understanding of the cellular heterogeneity of AML remains limited. In this study, we performed single-cell RNA sequencing (scRNAseq) of bone marrow-derived mononuclear cells obtained from same patients at different AML stages (diagnosis, CR, and relapse). We found that hematopoietic stem cells (HSCs) at diagnosis were abnormal compared to normal HSCs. By improving the detection of the DNMT3A R882 mutation with targeted scRNAseq, we identified that DNMT3A-mutant cells that mainly remained were granulocyte-monocyte progenitors (GMPs) or lymphoid-primed multipotential progenitors (LMPPs) from CR to relapse and that DNMT3A-mutant cells have gene signatures related to AML and leukemic cells. Copy number variation analysis at the single-cell level indicated that the cell type that possesses DNMT3A mutations is an important factor in AML relapse and that GMP and LMPP cells can affect relapse in patients with AML. This study advances our understanding of the role of DNMT3A in AML relapse and our approach can be applied to predict treatment outcomes.

• BMB Reports
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• 제57권5호
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• pp.232-237
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• 2024

This study investigated how adipose tissue-derived mesenchymal stem cells (AT-MSCs) respond to chondrogenic induction using droplet-based single-cell RNA sequencing (scRNA-seq). We analyzed 37,219 high-quality transcripts from control cells and cells induced for 1 week (1W) and 2 weeks (2W). Four distinct cell clusters (0-3), undetectable by bulk analysis, exhibited varying proportions. Cluster 1 dominated in control and 1W cells, whereas clusters (3, 2, and 0) exclusively dominated in control, 1W, and 2W cells, respectively. Furthermore, heterogeneous chondrogenic markers expression within clusters emerged. Gene ontology (GO) enrichment analysis of differentially expressed genes unveiled cluster-specific variations in key biological processes (BP): (1) Cluster 1 exhibited up-regulation of GO-BP terms related to ribosome biogenesis and translational control, crucial for maintaining stem cell properties and homeostasis; (2) Additionally, cluster 1 showed up-regulation of GO-BP terms associated with mitochondrial oxidative metabolism; (3) Cluster 3 displayed up-regulation of GO-BP terms related to cell proliferation; (4) Clusters 0 and 2 demonstrated similar up-regulation of GO-BP terms linked to collagen fibril organization and supramolecular fiber organization. However, only cluster 0 showed a significant decrease in GO-BP terms related to ribosome production, implying a potential correlation between ribosome regulation and the differentiation stages of AT-MSCs. Overall, our findings highlight heterogeneous cell clusters with varying balances between proliferation and differentiation before, and after, chondrogenic stimulation. This provides enhanced insights into the single-cell dynamics of AT-MSCs during chondrogenic differentiation.

• IMMUNE NETWORK
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• 제14권1호
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• pp.54-65
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• 2014

Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent, with the ability to differentiate into different cell types. Additionally, the immunomodulatory activity of MSCs can downregulate inflammatory responses. The use of MSCs to repair injured tissues and treat inflammation, including in neuroimmune diseases, has been extensively explored. Although MSCs have emerged as a promising resource for the treatment of neuroimmune diseases, attempts to define the molecular properties of MSCs have been limited by the heterogeneity of MSC populations. We recently developed a new method, the subfractionation culturing method, to isolate homogeneous human clonal MSCs (hcMSCs). The hcMSCs were able to differentiate into fat, cartilage, bone, neuroglia, and liver cell types. In this study, to better understand the properties of neurally differentiated MSCs, gene expression in highly homogeneous hcMSCs was analyzed. Neural differentiation of hcMSCs was induced for 14 days. Thereafter, RNA and genomic DNA was isolated and subjected to microarray analysis and DNA methylation array analysis, respectively. We correlated the transcriptome of hcMSCs during neural differentiation with the DNA methylation status. Here, we describe and discuss the gene expression profile of neurally differentiated hcMSCs. These findings will expand our understanding of the molecular properties of MSCs and contribute to the development of cell therapy for neuroimmune diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제17권12호
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• pp.5173-5177
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• 2016

Acute myeloid leukemia (AML), one of the most prevalent leukemia types in adults, demonstrates great heterogeneity in molecular and clinical terms. Hence, there is a necessity to the mechanisms involved in AML generation in order to determine optimal treatment. This cross sectional study aimed to assess changes in BECN1 gene expression in with blood samples from 30 AML patients, compared with samples from 15 healthy persons. RNA was extracted and cDNA was synthesized and Real Time PCR applied to determine BECN1 gene expression. The results showed no significant differences in BECN1 gene expression between patients with AML and normal controls (P > 0.05). It appears that expression of BECN1 does not play a significant role in genesis of AML leukemia.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1431-1434
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• 2015

Background: Breast cancer is one of the most common cancers among women worldwide and the HER2 receptor plays an important role in its development and progression. This systematic review aimed to summarize the role of HER2 in brain metastasis in patients with breast cancer. Materials and Methods: We conducted a literature search by advanced search in title field using the Scopus, Pubmed, and Google scholar databases until the end of June 2014. With metastasis, metastatic, HER2, brain, and breast cancer, as terms of search we selected 31 articles, which were reviewed by two independent and blinded expert reviewers. The studies were first selected according to their titles and abstracts. Quality of the studies were then assessed using the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) protocol for observational studies and CONSORT(Consolidation of Standards for Reporting Trials) protocol for clinical trials. For statistical analyses, we used STATA, version 11.0 software. Forest and funnel diagrams were drawn and for heterogeneity, index was also considered. Also we used meta regression analysis. Results: Finally, we reviewed 10 studies. The prevalence of brain metastasis in HER2-positive breast cancer patients was 24.9%. There was publication bias in the reviewed studies. Meta regression analysis showed that follow up time had no significant effect (p=0.396) on the prevalence of brain metastasis. Conclusions: The results showed a high prevalence of brain metastasis in HER2 positive breast cancer patients.

• The Plant Pathology Journal
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• 제18권5호
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• pp.259-265
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• 2002

Apple mosaic virus (ApMV), a member of the genus Ilarvirus, was detected and isolated from diseased 'Fuji' apple (Malus domestica) in Korea. The coat protein (CP) genes of two ApMV strains, denoted as ApMV-Kl and ApMV-K2, were amplified by using the reverse transcription and polymerase chain reaction (RT-PCR) and were analyzed thereafter. The objectives were to define the molecular variability of genomic information of ApMV found in Korea and to develop virus-derived resistant gene source for making virus-resistant trans-genic apple. RT-PCR amplicons for the APMVS were cloned and their nucleotide sequences were determined. The CPs of ApMV-Kl and ApMV-K2 consisted of 222 and 232 amino acid residues, respectively. The identities of the CPs of the two Korean APMVS were 93.1% and 85.6% at the nucleotide and amino acid sequences, respectively. The CP of ApMV-Kl showed 46.1-100% and 43.2-100% identities to eight different ApMV strains at the nucleotide and amino acid levels, respectively. When ApMV-PV32 strain was not included in the analysis, ApMV strains shared over 83.0% and 78.6% homologies at the nucleotide and amino acid levels, respectively. ApMV strains showed heterogeneity in CP size and sequence variability. Most of the amino acid residue differences were located at the N-termini of the strains of ApMV, whereas, the middle regions and C-termini were remarkably conserved. The APMVS were 17.(1-54.5% identical with three other species of the genus Ilarviyus. ApMV strains can be classified into three subgroups (subgroups I, II, and III) based on the phylogenetic analysis of CP gene in both nucleotide and amino acid levels. Interestingly, all the strains of subgroup I were isolated from apple plants, while the strains of subgroups II and III were originated from peach, hop, or pear, The results suggest that ApMV strains co-evolved with their host plants, which may have resulted in the CP heterogeneity.

• Korean Journal of Radiology
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• 제22권12호
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• pp.2082-2093
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• 2021

Objective: We conducted a systematic review and meta-analysis of the tissue adequacy and complication rates of percutaneous transthoracic needle biopsy (PTNB) for molecular analysis in patients with non-small cell lung cancer (NSCLC). Materials and Methods: We performed a literature search of the OVID-MEDLINE and Embase databases to identify original studies on the tissue adequacy and complication rates of PTNB for molecular analysis in patients with NSCLC published between January 2005 and January 2020. Inverse variance and random-effects models were used to evaluate and acquire meta-analytic estimates of the outcomes. To explore heterogeneity across the studies, univariable and multivariable metaregression analyses were performed. Results: A total of 21 studies with 2232 biopsies (initial biopsy, 8 studies; rebiopsy after therapy, 13 studies) were included. The pooled rates of tissue adequacy and complications were 89.3% (95% confidence interval [CI]: 85.6%-92.6%; I² = 0.81) and 17.3% (95% CI: 12.1%-23.1%; I² = 0.89), respectively. These rates were 93.5% and 22.2% for the initial biopsies and 86.2% and 16.8% for the rebiopsies, respectively. Severe complications, including pneumothorax requiring chest tube placement and massive hemoptysis, occurred in 0.7% of the cases (95% CI: 0%-2.2%; I² = 0.67). Multivariable meta-regression analysis showed that the tissue adequacy rate was not significantly lower in studies on rebiopsies (p = 0.058). The complication rate was significantly higher in studies that preferentially included older adults (p = 0.001). Conclusion: PTNB demonstrated an average tissue adequacy rate of 89.3% for molecular analysis in patients with NSCLC, with a complication rate of 17.3%. PTNB is a generally safe and effective diagnostic procedure for obtaining tissue samples for molecular analysis in NSCLC. Rebiopsy may be performed actively with an acceptable risk of complications if clinically required.

• 공업화학
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• 제7권2호
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• pp.341-349
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• 1996

폴리우레탄 수지의 염색성을 향상시키기 위하여 염착좌석을 갖는 저분자량의 디올류를 쇄연장제로 활용하였다. 쇄연장제와 폴리올의 종류를 변화시키고, 또한 하드세그멘트 (HS)/소프트세그멘트 (SS) 비율을 변화시키면서 폴리우레탄 수지를 합성하였다. HS/SS가 1.4이고, dimethylolpropionic acld(DMPA), N-butyldiethanolamine(BDEA)를 염착좌석용 쇄연장제(DCE)로 활용한 경우 반응의 불균일성으로 인하여 기계적 물성이 좋지 못하였으며, 특히 에스테르계 폴리올인 poly(butylene/ethylene adipate) glycol(PBEAG)로 합성한 경우 내가수분해성이 현저히 저하되었다. 그러나 DCE로 N-methyldiethanol amine(MDEA)를 사용하고 HS/SS를 1.3으로 조절한 경우 기계적 물성과 염색성이 향상되었으며, MDEA를 선형 쇄연장제(CE)인 1,4-butanediol(1,4-BD)과 에테르형 폴리올인 poly[oxyteramethylene] glycol(PTMG)과 반응시킨 경우 기계적 물성과 내가수분해성이 현저하게 향상되었다. 특히 분자설계적 측면에서 DCE를 HS와 SS내의 배분과 1,6-hexanediol(1,6-HD) 및 neopentylglycol(NPG)과의 공쇄연장으로 초기탄성률, 인장강도, 신장률을 제어 할 수 있음을 알 수 있다.

• 생물정신의학
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• 제18권3호
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• pp.109-118
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• 2011

Objectives Many studies have suggested different neurobiological findings and clinical courses in alcoholism. Recently, subtyping in alcohol dependence has become essential to overcome the heterogeneity of patients. Among several criteria of subtypes, Lesch's typology is proposed to integrate biological, social, and psychological factors. This review provides neurobiological findings and treatment-responses of alcohol dependence according to Lesch's typology. Method We searched the international published medical literature using the search terms 'Lesch's typology' and 'alcohol dependence' and using the limits 'human'. Results We identified 17 studies with subjects of alcohol dependence according to Lesch's typology. Conclusion They indicated that each subtype of Lesch's typology can have specific neurobiological factors and different clinical responses as follows. Lesch's subtype 1 is characterized by severe withdrawal symptoms and associated with elevated glutamate and homocysteine. Lesch's subtype 2 is defined by individuals who drink alcohol as self-medication for anxiety. Their craving has significant positive correlations with prolactin, leptin level, or intake-volume (vasopressin). Lesch's subtype 4 is related to cerebral dysfunction and associated with increased glutamate and left-handedness. Clinical trials showed that naltrexone was effective in Lesch's subtype 3 and 4 patients, while acamprosate was effective in the subtypes 1 and 2.

• 생물정신의학
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• 제10권2호
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• pp.159-167
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• 2003

Objective:Under the hypothesis that 5-HTTLPR polymorphism plays some role in the susceptibility or vulnerability of some subgroup of alcohol dependence, associations of 5-HTTLPR polymorphism with alcohol dependence were examined. Method:This association analysis included 109 Korean alcohol dependent and 113 Korean control subjects. DNA of all subjects were genotyped for the biallelic functional polymorphism in the 5-HTTLPR. Considering the likelihood of heterogeneity in the alcohol dependence phenotype, alcohol dependent subjects were subgrouped by onset age, family history of alcohol dependence and severity of withdrawal symptoms. Results:There were no significant differences in the frequencies of either the 5-HTTLPR genotype or the short vs. long allele in alcohol dependent and control subjects. The frequency of the S allele and S-carrier (LS or SS genotype) was significantly increased in the early onset alcohol dependent subjects and the familial alcohol dependent subjects compared with that in the control subjects. Conclusion:The results suggest that the 5-HTT 'S' promoter polymorphism is associated with an increased susceptibility or vulnerability to develop early onset alcohol dependence and familial alcohol dependence, which characterize Cloninger's type 2 alcohol dependence.