Publications by authors named "Ji-Yun Lee"

204 Publications

Evaluation of the need for cytoreduction and its potential carcinogenicity in children and young adults with myeloproliferative neoplasms.

Ann Hematol 2021 Oct 30;100(10):2567-2574. Epub 2021 Jul 30.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam-si, 13620, Gyeonggi-do, Republic of Korea.

Myeloproliferative neoplasms are rare at a young age, and few reports have described the disease characteristics and outcomes in this group. This study aimed to elucidate the clinical course of essential thrombocythemia (ET) and polycythemia vera (PV) in children and young adults aged <39 years focusing on thromboembolic events (TE) and second primary malignancies (SPMs). A total of 990 patients who were diagnosed from 2008 to 2017 were included by analyzing the Health Insurance Review and Assessment Service database in Korea. The incidence was 2.53 per 1,000,000 for ET (643 patients; 276 male patients; median 31 years) and 1.37 per 1,000,000 for PV (347 patients; 309 male patients; median 32 years). Three ET patients developed secondary acute myelogenous leukemia and three developed secondary myelofibrosis. The 5-year cumulative incidence of TE was 14.2% in ET and 21.3% in PV. Thus, the incidence was higher in PV; in particular, arterial TE (ATE) was evidently higher in PV than in ET. The 5-year cumulative incidence of SPMs was 2.5% in ET and 2.6% in PV. While the use of both aspirin and hydroxyurea reduced the incidence of ATE, hydroxyurea significantly increased the incidence of SPMs. The incidence of ET and PV was very low, and ET was more common than PV in children and young adults. The high incidence of TE in young patients suggests the importance of thrombosis prevention. However, hydroxyurea appears to increase the incidence of SPMs; therefore, the risks and benefits should be considered.
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http://dx.doi.org/10.1007/s00277-021-04527-7DOI Listing
October 2021

Is loss of smell an early predictor of COVID-19 severity: a systematic review and meta-analysis.

Arch Pharm Res 2021 Jul 24;44(7):725-740. Epub 2021 Jul 24.

Evidence-Based Research Laboratory, Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, South Korea.

Anecdotal evidence suggests that the severity of coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is likely to be distinguished by variations in loss of smell (LOS). Thus, we conducted a meta-analysis of 45 articles that include a total of 42,120 COVID-19 patients from 17 different countries to demonstrate that severely ill or hospitalized COVID-19 patients have a lesser chance of experiencing LOS than non-severely ill or non-hospitalized COVID-19 patients (odds ratio = 0.527 [95% CI 0.373-0.744; p < 0.001] and 0.283 [95% CI 0.173-0.462; p < 0.001], respectively). We also proposed a possible mechanism underlying the association of COVID-19 severity with anosmia, which may explain why patients without sense of smell develop severe COVID-19. Variations in LOS according to the severity of COVID-19 is a global phenomenon, with few exceptions. Since severely ill patients have a lower rate of anosmia, patients without anosmia should be monitored more closely in the early stages of COVID-19, for early diagnosis of severity of illness. An understanding of how the severity of COVID-19 infection and LOS are associated has profound implications for the clinical management and mitigation strategies for the disease.
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http://dx.doi.org/10.1007/s12272-021-01344-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302975PMC
July 2021

Anti-inflammatory effect of Ailanthus altissima (Mill.) Swingle leaves in lipopolysaccharide-stimulated astrocytes.

J Ethnopharmacol 2021 Jul 13:114258. Epub 2021 Jul 13.

Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, Republic of Korea. Electronic address:

Ethnopharmacological Relevance: Activated astrocytes are involved in the progression of neurodegenerative diseases. Traditionally, Ailanthus altissima (Mill.) Swingle, widely distributed in East Asia, has been used as a medicine for the treatment of fever, gastric diseases, and inflammation. Although A. altissima has been reported to play an anti-inflammatory role in peripheral tissues or cells, its role in the central nervous system (CNS) remains unclear.

Aim Of The Study: In the present study, we investigated the anti-inflammatory effects and mechanism of action of A. altissima in primary astrocytes stimulated by lipopolysaccharide (LPS).

Materials And Methods: A nitrite assay was used to measure nitric oxide (NO) production, and the tetrazolium salt 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was performed to determine cytotoxicity. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and mitogen-activated protein kinase (MAPK) were determined with western blotting. Reverse-transcription PCR was used to assess the expression of inflammatory cytokines. The levels of reactive oxygen species were measured using 2,7-dichlorodihydrofluorescein diacetate. Luciferase assay and immunocytochemistry were used for assessing nuclear factor-kappa B (NF-κB) transcription and p65 localization, respectively. Memory and social interaction were analyzed using the Y-maze and three-chamber tests, respectively.

Results: The ethanol extract of A. altissima leaves (AAE) inhibited iNOS and COX-2 expression in LPS-stimulated astrocytes. Moreover, AAE reduced the transcription of various proinflammatory mediators, hindered NF-κB activation, and suppressed extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activation without p38 activation. Ultra-high performance liquid chromatography with mass spectrometry analysis revealed that AAE comprised ethyl gallate, quercetin, and kaempferol, along with luteolin, which has anti-inflammatory properties, and repressed LPS-induced nitrite levels and the nuclear translocation of p65. Finally, oral administration of AAE attenuated LPS-induced memory and social impairment in mice and repressed LPS-induced ERK and JNK activation in the cortices of mice.

Conclusion: AAE could have therapeutic uses in the treatment of neuroinflammatory diseases via suppression of astrocyte activation.
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http://dx.doi.org/10.1016/j.jep.2021.114258DOI Listing
July 2021

Kidney injury molecule-1 inhibits metastasis of renal cell carcinoma.

Sci Rep 2021 Jun 4;11(1):11840. Epub 2021 Jun 4.

Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.

Metastasis is present in approximately 30% of patients diagnosed with renal cell carcinoma (RCC) and is associated with a 5-year survival rate of < 15%. Kidney injury molecule 1 (KIM-1), encoded by the HAVCR1 gene, is a proximal tubule cell-surface glycoprotein and a biomarker for early detection of RCC, but its pathophysiological significance in RCC remains unclear. We generated human and murine RCC cell lines either expressing or lacking KIM-1, respectively, and compared their growth and metastatic properties using validated methods. Surprisingly, KIM-1 expression had no effect on cell proliferation or subcutaneous tumour growth in immune deficient (Rag1) Balb/c mice, but inhibited cell invasion and formation of lung metastasis in the same model. Further, we show that the inhibitory effect of KIM-1 on metastases was observed in both immune deficient and immune competent mice. Transcriptomic profiling identified the mRNA for the pro-metastatic GTPase, Rab27b, to be downregulated significantly in KIM-1 expressing human and murine RCC cells. Finally, analysis of The Cancer Genome Atlas (TCGA) data revealed that elevated HAVCR1 mRNA expression in the two most common types of RCC, clear cell and papillary RCC, tumours correlated with significantly improved overall patient survival. Our findings reveal a novel role for KIM-1 in inhibiting metastasis of RCC and suggests that tumour-associated KIM-1 expression may be a favourable prognostic factor.
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http://dx.doi.org/10.1038/s41598-021-90919-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178330PMC
June 2021

A Case of Paraneoplastic Pemphigus as a Preceding Manifestation of Underlying Follicular Lymphoma Treated with R-CHOP.

Ann Dermatol 2021 Jun 4;33(3):271-274. Epub 2021 May 4.

Department of Dermatology, Seoul National University Bundang Hospital, Seongnam, Korea.

Paraneoplastic pemphigus is a rare, life-threatening disorder associated with an underlying neoplasm, which presents with painful stomatitis and polymorphous skin lesions. Successful diagnosis of paraneoplastic pemphigus can lead to the diagnosis and treatment of the underlying malignancy. However, involvement of the respiratory system is typically unresponsive to treatment. Herein, we report the case of a 44-year-old female diagnosed with paraneoplastic pemphigus with underlying follicular lymphoma treated with a chemotherapy regimen including rituximab. Her skin lesions and underlying lymphoma responded to treatment, but bronchiolitis obliterans continued to progress and resulted in fatal respiratory failure.
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http://dx.doi.org/10.5021/ad.2021.33.3.271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137331PMC
June 2021

Novel QTL Associated with Shoot Branching Identified in Doubled Haploid Rice ( L.) under Low Nitrogen Cultivation.

Genes (Basel) 2021 05 14;12(5). Epub 2021 May 14.

Department of Southern Area Crop Science, National Institute of Crop Science, RDA, Miryang 50424, Korea.

Shoot branching is considered as an important trait for the architecture of plants and contributes to their growth and productivity. In cereal crops, such as rice, shoot branching is controlled by many factors, including phytohormones signaling networks, operating either in synergy or antagonizing each other. In rice, shoot branching indicates the ability to produce more tillers that are essential for achieving high productivity and yield potential. In the present study, we evaluated the growth and development, and yield components of a doubled haploid population derived from a cross between 93-11 (P1, ) and Milyang352 (P2, ), grown under normal nitrogen and low nitrogen cultivation open field conditions. The results of the phenotypic evaluation indicated that parental lines 93-11 (P1, a high tillering cultivar) and Milyang352 (P2, a low tillering cultivar) showed distinctive phenotypic responses, also reflected in their derived population. In addition, the linkage mapping and quantitative trait locus (QTL) analysis detected three QTLs associated with tiller number on chromosome 2 (, 130 cM, logarithm of the odds (LOD) 4.14, PVE 14.5%; and , 134 cM, LOD: 6.05, PVE: 20.5%) and chromosome 4 (, 134 cM, LOD 3.92, PVE 14.5%), with having the highest phenotypic variation explained, and the only QTL associated with tiller number under low nitrogen cultivation conditions, using Kompetitive Allele-Specific PCR (KASP) and Fluidigm markers. The additive effect (1.81) of indicates that the allele from 93-11 (P1) contributed to the observed phenotypic variation for tiller number under low nitrogen cultivation. The breakthrough is that the majority of the candidate genes harbored by the QTLs and (here associated with the control of shoot branching under low and normal nitrogen cultivation, respectively), were also proposed to be involved in plant stress signaling or response mechanisms, with regard to their annotations and previous reports. Therefore, put together, these results would suggest that a possible crosstalk exists between the control of plant growth and development and the stress response in rice.
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http://dx.doi.org/10.3390/genes12050745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157147PMC
May 2021

Diversity of Acupuncture Point Selections According to the Acupuncture Styles and Their Relations to Theoretical Elements in Traditional Asian Medicine: A Data-Mining-Based Literature Study.

J Clin Med 2021 May 11;10(10). Epub 2021 May 11.

Department of Physiology, College of Korean Medicine, Dongguk University, Gyeongju 38066, Korea.

Acupuncture point (AP) selections can vary depending on clinicians' acupuncture style, and therefore, acupuncture style is an important factor in determining the efficacy of acupuncture treatment. However, few studies have examined the differences in AP selections according to the acupuncture styles and theoretical backgrounds causing the differences. We compared the AP prescriptions used for 14 diseases in three classical medical textbooks, (DEBG), (SADI), and (CGGHB), which represent unique acupuncture styles and have affected clinicians during this time. AP prescriptions showed more diversity between textbooks than between types of diseases. Among the three textbooks, AP prescriptions of SADI were most different compared to those of DEBG and CGGHB. Importantly, we found each style can be more clearly explained by AP attributes than by the APs per se. Specifically, SADI, DEBG, and CGGHB preferred located on the limbs, APs of the , and , respectively. This suggests the possibility that the theoretical diversity of acupuncture styles results in the heterogeneity of AP selections.
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http://dx.doi.org/10.3390/jcm10102059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151004PMC
May 2021

EGR1 as a potential marker of prognosis in extranodal NK/T-cell lymphoma.

Sci Rep 2021 May 14;11(1):10342. Epub 2021 May 14.

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.

Extranodal natural killer T-cell lymphoma (ENKTL) is an aggressive malignancy with a dismal prognosis. In the present study, gene expression profiling was performed to provide more information on ENKTL molecular signature and offer a rationale for further investigation of prognostic markers in ENKTL. NanoString nCounter Analysis encompassing 133 target genes was used to compare gene expression levels of 43 ENKTL tumor samples. The majority of the patients were under 60 years of age (79.1%); 32 (74.4%) patients had nasal type ENKTL and 23 patients (53.5%) had intermediate/high risk ENKTL based on the prognostic index for natural killer cell lymphoma (PINK). The median follow-up was 15.9 months and the median overall survival (OS) was 16.1 months (95% CI 13.0-69.8). EGR1 upregulation was consistently identified in the localized stage with a low risk of prognostic index based on the PINK. Among the six significantly relevant genes for EGR1 expression, high expression levels of genes, including CD59, GAS1, CXCR7, and RAMP3, were associated with a good survival prognosis. The in vitro test showed EGR1 modulated the transcriptional activity of the target genes including CD59, GAS1, CXCR7, and RAMP3. Downregulation of EGR1 and its target genes significantly inhibited apoptosis and decreased chemosensitivity and attenuated radiation-induced apoptosis. The findings showed EGR1 may be a candidate for prognostic markers in ENKTL. Considerable additional characterization may be necessary to fully understand EGR1.
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http://dx.doi.org/10.1038/s41598-021-89754-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121831PMC
May 2021

Vinpocetine alleviates lung inflammation via macrophage inflammatory protein-1β inhibition in an ovalbumin-induced allergic asthma model.

PLoS One 2021 29;16(4):e0251012. Epub 2021 Apr 29.

College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.

Asthma is a well-known bronchial disease that causes bronchial inflammation, narrowing of the bronchial tubes, and bronchial mucus secretion, leading to bronchial blockade. In this study, we investigated the association between phosphodiesterase (PDE), specifically PDE1, and asthma using 3-isobutyl-1-methylxanthine (IBMX; a non-specific PDE inhibitor) and vinpocetine (Vinp; a PDE1 inhibitor). Balb/c mice were randomized to five treatment groups: control, ovalbumin (OVA), OVA + IBMX, OVA + Vinp, and OVA + dexamethasone (Dex). All mice were sensitized and challenged with OVA, except for the control group. IBMX, Vinp, or Dex was intraperitoneally administered 1 h before the challenge. Vinp treatment significantly inhibited the increase in airway hyper-responsiveness (P<0.001) and reduced the number of inflammatory cells, particularly eosinophils, in the lungs (P<0.01). It also ameliorated the damage to the bronchi and alveoli and decreased the OVA-specific IgE levels in serum, an indicator of allergic inflammation increased by OVA (P<0.05). Furthermore, the increase in interleukin-13, a known Th2 cytokine, was significantly decreased by Vinp (P<0.05), and Vinp regulated the release and mRNA expression of macrophage inflammatory protein-1β (MIP-1β) increased by OVA (P<0.05). Taken together, these results suggest that PDE1 is associated with allergic lung inflammation induced by OVA. Thus, PDE1 inhibitors can be a promising therapeutic target for the treatment of asthma.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251012PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084130PMC
April 2021

Recombinant apoptosis inhibitor of macrophage protein reduces delayed graft function in a murine model of kidney transplantation.

PLoS One 2021 23;16(4):e0249838. Epub 2021 Apr 23.

Department of Microbiology and Immunology, Western University, London, Ontario, Canada.

Reperfusion injury following cold and warm ischemia (IRI) is unavoidable during kidney transplantation and contributes to delayed graft function (DGF) and premature graft loss. Death of tubular epithelial cells (TECs) by necrosis during IRI releases pro-inflammatory mediators (e.g. HMGB1), propagating further inflammation (necroinflammation) and tissue damage. Kidney Injury Molecule-1 (KIM-1) is a phagocytic receptor upregulated on proximal TECs during acute kidney injury. We have previously shown that renal KIM-1 protects the graft against transplant associated IRI by enabling TECs to clear apoptotic and necrotic cells, and that recognition of necrotic cells by KIM-1 is augmented in the presence of the opsonin, apoptosis inhibitor of macrophages (AIM). Here, we tested whether recombinant AIM (rAIM) could be used to mitigate transplant associated IRI. We administered rAIM or vehicle control to nephrectomised B6 mice transplanted with a single B6 donor kidney. Compared to grafts in vehicle-treated recipients, grafts from rAIM-treated mice exhibited significantly less renal dysfunction, tubular cell death, tissue damage, tubular obstruction, as well as local and systemic inflammation. Both mouse and human rAIM enhanced the clearance of necrotic cells by murine and human TECs, respectively in vitro. These data support testing of rAIM as a potential therapeutic agent to reduce DGF following kidney transplantation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249838PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064555PMC
April 2021

A phase II study of brentuximab vedotin in patients with relapsed or refractory Epstein-Barr virus-positive and CD30-positive lymphomas.

Haematologica 2021 Aug 1;106(8):2277-2280. Epub 2021 Aug 1.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Seoul National University Cancer Research Institute, Seoul.

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http://dx.doi.org/10.3324/haematol.2021.278301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327727PMC
August 2021

New Insights into the Transcriptional Regulation of Genes Involved in the Nitrogen Use Efficiency under Potassium Chlorate in Rice ( L.).

Int J Mol Sci 2021 Feb 22;22(4). Epub 2021 Feb 22.

Department of Southern Area Crop Science, National Institute of Crop Science, RDA, Miryang 50424, Korea.

Potassium chlorate (KClO) has been widely used to evaluate the divergence in nitrogen use efficiency (NUE) between and rice subspecies. This study investigated the transcriptional regulation of major genes involved in the NUE in rice treated with KClO, which acts as an inhibitor of the reducing activity of nitrate reductase (NR) in higher plants. A set of two KClO sensitive nitrate reductase (NR) and two nitrate transporter (NRT) introgression rice lines (BC2F7), carrying the alleles of NR or NRT, derived from a cross between Saeilmi (, P1) and Milyang23 (, P2), were exposed to KClO at the seedling stage. The phenotypic responses were recorded 7 days after treatment, and samples for gene expression, physiological, and biochemical analyses were collected at 0 h (control) and 3 h after KClO application. The results revealed that Saeilmi (P1, ) and Milyang23 (P2, ) showed distinctive phenotypic responses. In addition, the expression of was differentially regulated between the roots, stem, and leaf tissues, and between introgression lines. When expressed in the roots, was downregulated in all introgression lines. However, in the stem and leaves, was upregulated in the NR introgression lines, but downregulation in the NRT introgression lines. In the same way, the expression patterns of and in the roots, stem, and leaves indicated a differential transcriptional regulation by KClO, with prevailing over in the roots. Under the same conditions, the activity of NR was inhibited in the roots and differentially regulated in the stem and leaf tissues. Furthermore, the transcriptional divergence of and , and between NR and NRT, coupled with the NR activity pattern in the roots, would indicate the prevalence of nitrate (NO¯) transport over ammonium (NH) transport. Moreover, the induction of catalase (CAT) and polyphenol oxidase (PPO) enzyme activities in Saeilmi (P1, KClO resistant), and the decrease in Milyang23 (P2, KClO sensitive), coupled with the malondialdehyde (MDA) content, indicated the extent of the oxidative stress, and the induction of the adaptive response mechanism, tending to maintain a balanced reduction-oxidation state in response to KClO. The changes in the chloroplast pigments and proline content propose these compounds as emerging biomarkers for assessing the overall plant health status. These results suggest that the inhibitory potential of KClO on the reduction activity of the nitrate reductase (NR), as well as that of the genes encoding the nitrate and ammonium transporters, and glutamate synthase are tissue-specific, which may differentially affect the transport and assimilation of nitrate or ammonium in rice.
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http://dx.doi.org/10.3390/ijms22042192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926690PMC
February 2021

Parl. Extracts Reduce Acute Inflammation by Targeting Oxidative Stress.

Evid Based Complement Alternat Med 2021 13;2021:7924645. Epub 2021 Jan 13.

College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.

Parl. (PTP) has traditionally been used for edible and medicinal purposes to treat several disorders, including diabetes and neuralgia. Therefore, this study sought to evaluate the inhibitory effects of PTP leaf ethanol extracts on acute inflammation. Moreover, the reactive oxygen species (ROS) scavenging activity, superoxide dismutase (SOD) activity, lipopolysaccharide (LPS)-induced nitric oxide (NO) generation, and HO-induced lipid peroxidation capacity of PTP were assessed in RAW 264.7 macrophages. Our results suggest that PTP prevents cell damage caused by oxidative free radicals and downregulates the expression of LPS-induced inflammation-associated factors including inducible nitric oxidase synthetase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E (PGE). PTP inhibited NO production by 53.5% ( < 0.05) and iNOS expression by 71.5% ( < 0.01) at 100 g/mL. PTP at 100 g/mL also inhibited ROS generation by 58.2% ( < 0.01) and SOD activity by 29.3%, as well as COX-2 expression by 83.3% ( < 0.01) and PGE2 expression by 98.6% ( < 0.01). The anti-inflammatory effects of PTP were confirmed using an arachidonic acid (AA)-induced ear edema mouse model. Ear thickness and myeloperoxidase (MPO) activity were evaluated as indicators of inflammation. PTP inhibited edema formation by 64.5% ( < 0.05) at 1.0 mg/ear. A total of 16 metabolites were identified in PTP extracts and categorized into subgroups, including two phenolic acids (mainly quinic acid), seven flavonoids, five lignans, one sesquiterpenoid, and one long-chain fatty acid. Therefore, our results suggest that PTP possesses anti-inflammatory properties.
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http://dx.doi.org/10.1155/2021/7924645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817271PMC
January 2021

Risk of Hematologic Malignant Neoplasms From Abdominopelvic Computed Tomographic Radiation in Patients Who Underwent Appendectomy.

JAMA Surg 2021 Apr;156(4):343-351

Department of Radiology, Seoul National University Bundang Hospital, Gyeonggi-do, Korea.

Importance: Whether computed tomography (CT) radiation is truly carcinogenic remains controversial. Large epidemiological studies that purportedly showed an association between CT radiation and carcinogenesis were limited by confounding by indication and reverse causation, because the reasons for CT examination were unknown.

Objective: To measure the risk of hematologic malignant neoplasms associated with perioperative abdominopelvic CT radiation among patients who underwent appendectomy for acute appendicitis.

Design, Setting, And Participants: This nationwide population-based cohort study used the National Health Insurance Service claims database in South Korea to assess 825 820 patients who underwent appendectomy for appendicitis from January 1, 2005, to December 31, 2015, and had no underlying risk factors for cancer. Patients were divided into CT-exposed (n = 306 727) or CT-unexposed (n = 519 093) groups. The study was terminated on December 31, 2017, and data were analyzed from October 30, 2018, to September 27, 2020.

Exposures: Perioperative abdominopelvic CT examination from 7 days before to 7 days after appendectomy.

Main Outcomes And Measures: The primary outcome was the incidence rate ratio (IRR) of hematologic malignant neoplasms for both groups. The secondary outcomes were IRR of abdominopelvic organ cancers and IRR of all cancers. The lag period was 2 years for the primary outcome and 5 years for secondary outcomes. The IRRs were calculated using Poisson regression models with adjustment for age and sex.

Results: Among the study population of 825 820 patients (52.9% male; median age, 28 [interquartile range, 15-41] years), hematologic malignant neoplasms developed in 323 patients in the CT-exposed group during 1 486 518 person-years and 500 patients in the CT-unexposed group during 3 422 059 person-years. For all hematologic malignant neoplasms, the IRR for the CT-exposed vs CT-unexposed group was 1.26 (95% CI, 1.09-1.45; P = .002). In terms of individual categories of hematologic malignant neoplasms, the CT-exposed group had an elevated risk only for leukemia (IRR, 1.40 [98.75% CI, 1.04-1.87, adjusted by Bonferroni correction]; P = .005). There was no between-group difference in incidence rate of abdominopelvic organ cancers (IRR, 1.07 [95% CI, 1.00-1.15]; P = .06) and that of all cancers (IRR, 1.04 [95% CI, 0.99-1.09]; P = .14).

Conclusions And Relevance: This study controlled for reverse causation bias by defining the reasons for CT scan, and findings suggest that abdominopelvic CT radiation is associated with a higher incidence of hematologic malignant neoplasms. Efforts should be continued for judicious use of CT examinations.
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http://dx.doi.org/10.1001/jamasurg.2020.6357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047726PMC
April 2021

Carfilzomib in addition to lenalidomide and dexamethasone in Asian patients with RRMM outside of a clinical trial.

Ann Hematol 2021 Aug 15;100(8):2051-2059. Epub 2021 Jan 15.

Department of Hematology, Seoul St. Mary's Hematology Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.

Carfilzomib, lenalidomide, and dexamethasone (KRd) effectively improve survival in patients with relapsed and refractory multiple myeloma (RRMM). However, the outcome of KRd treatment in Asian patients reflecting a general RRMM population outside of a clinical trial has not been reported. Fifty-five RRMM patients who were treated with carfilzomib in combination with Rd from the time of the first approval of KRd in the Republic of Korea were analyzed. The median age was 61 years. The percentage of patients with an ECOG performance status ≥ 3, creatinine clearance < 50 mL/min, high-risk cytogenetics, and ≥ 4 lines of prior treatment were 9%, 22%, 31%, and 27%, respectively. Forty-one patients started treatment with KRd, whereas the remaining 14 patients (25%) were added carfilzomib during the Rd treatment. In the whole cohort, the overall response rate was 73% and progression-free survival was 8.8 months. The addition of carfilzomib in patients who were refractory or had disease progression during Rd treatment reattained a response in half of the patients. The advantage of carfilzomib with Rd was significant in patients in the first relapse. Toxicity profile was acceptable, excluding severe infections. Carfilzomib in combination with Rd is effective and has a reasonable adverse event rate in Asian patients with RRMM.
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http://dx.doi.org/10.1007/s00277-021-04407-0DOI Listing
August 2021

Nrf2 regulates cell motility through RhoA-ROCK1 signalling in non-small-cell lung cancer cells.

Sci Rep 2021 01 13;11(1):1247. Epub 2021 Jan 13.

Department of Pathology, Korea University College of Medicine, 73, Goryeodae-ro, Seongbuk-gu, Seoul, 02841, South Korea.

Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of several antioxidant and anti-inflammatory enzymes. It binds to its endogenous inhibitor Kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm under normal conditions. Various endogenous or environmental oxidative stresses can disrupt the Nrf2/Keap1 complex, allowing Nrf2 to translocate into the nucleus, where it induces the transcription of various cytoprotective enzymes by binding to antioxidant responsive elements. These enzymes have been reported to play a role in regulating tumour growth, angiogenesis, and chemoprevention. Invasion and migration are the most harmful aspects of cancer; they directly impacts the patients' survival. Although the roles of Keap1/Nrf2 and their downstream genes in various cancers have been widely documented, their role in regulating cell motility still remains unclear, particularly in cancer cells. We observed that Nrf2 suppression following treatment with brusatol in non-small-cell lung cancer (NSCLC) cells with either exogenously introduced Keap1 or siNrf2 resulted in the inhibition of cell migration and invasion, with shrinking cell morphology due to decreased focal adhesions via inhibition of the RhoA-ROCK1 pathway. Nrf2 overexpression showed opposite results. Thus, the Nrf2/Keap1 pathway may affect cell motility by dysregulating the RhoA-ROCK1 signalling pathway in NSCLC.
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http://dx.doi.org/10.1038/s41598-021-81021-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806835PMC
January 2021

Serodiagnostic antigens of Clonorchis sinensis identified and evaluated by high-throughput proteogenomics.

PLoS Negl Trop Dis 2020 12 28;14(12):e0008998. Epub 2020 Dec 28.

Department of Tropical Medicine, Inha University School of Medicine, Incheon, Korea.

Clonorchiasis caused by Clonorchis sinensis is endemic in East Asia; approximately 15 million people have been infected thus far. To diagnose the infection, serodiagnostic tests with excellent functionality should be performed. First, 607 expressed sequence tags encoding polypeptides with a secretory signal were expressed into recombinant proteins using an in vitro translation system. By protein array-based screening using C. sinensis-infected sera, 18 antigen candidate proteins were selected and assayed for cross-reactivity against Opisthorchis viverrini-infected sera. Of the six antigenic proteins selected, four were synthesized on large scale in vitro and evaluated for antigenicity against the flukes-infected human sera using ELISA. CsAg17 antigen showed the highest sensitivity (77.1%) and specificity (71.2%). The sensitivity and specificity of the bacterially produced CsAg17-28GST fusion antigen was similar to those of CsAg17 antigen. CsAg17 antigen can be used to develop point-of-care serodiagnostic tests for clonorchiasis.
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http://dx.doi.org/10.1371/journal.pntd.0008998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793300PMC
December 2020

Sodium-bile acid co-transporter is crucial for survival of a carcinogenic liver fluke Clonorchis sinensis in the bile.

PLoS Negl Trop Dis 2020 12 7;14(12):e0008952. Epub 2020 Dec 7.

Department of Medical Environmental Biology, Chung-Ang University College of Medicine, Seoul, Republic of Korea.

The liver fluke Clonorchis sinensis inhabits the bile ducts, where bile concentration disparities across the fluke cell membrane can cause bile intoxication. Sodium-bile acid co-transporter (SBAT) plays a crucial role in bile acid recycling. The process by which SBAT imports bile acids is electrically coupled to sodium ion co-transportation. Here, we report that the SBAT of C. sinensis (CsSBAT) is involved in bile acid transportation. CsSBAT cDNA encoded a putative polypeptide of 546 amino acid residues. Furthermore, CsSBAT consisted of ten putative transmembrane domains, and its 3D structure was predicted to form panel and core domains. The CsSBAT had one bile acid- and three Na+-binding sites, enabling coordination of a symport process. CsSBAT was mainly localized in the mesenchymal tissue throughout the fluke body and sparsely localized in the basement of the tegument, intestinal epithelium, and excretory bladder wall. Bile acid permeated into the adult flukes in a short time and remained at a low concentration level. Bile acid accumulated inside the mesenchymal tissue when CsSBAT was inhibited using polyacrylic acid-tetradeoxycholic acid conjugate. The accumulated bile acid deteriorated the C. sinensis adults leading to death. CsSBAT silencing shortened the lifespan of the fluke when it was placed into bile. Taken together, we propose that CsSBAT transports bile acids in the mesenchymal tissue and coordinate with outward transporters to maintain bile acid homeostasis of C. sinensis adults, contributing to C. sinensis survival in the bile environment.
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http://dx.doi.org/10.1371/journal.pntd.0008952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746286PMC
December 2020

Pneumocystis jirovecii pneumonia in diffuse large B-cell Lymphoma treated with R-CHOP.

Mycoses 2021 Jan 28;64(1):60-65. Epub 2020 Oct 28.

Division of Hematology-Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Background: The aim of this study was to estimate the incidence of and risk factors for Pneumocystis pneumonia (PCP) infection in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP).

Methods: The medical records of 739 DLBCL patients who received R-CHOP between May 2004 and January 2019 were retrospectively evaluated. Patients were divided into two groups: those who received primary PCP prophylaxis (prophylaxis group) and those who did not (control group). The incidence rate of PCP in each group was calculated, and risk factors for PCP were evaluated in the control group.

Results: Baseline characteristics were significantly different between the two groups. Compared to the 602 patients who did not receive prophylaxis, the prophylaxis group (n = 137) had poor prognostic factors of older age, high lactate dehydrogenase (LDH) levels, advanced Ann Arbour stage, and high International Prognostic Index (IPI) risk scores. None of the patients receiving PCP prophylaxis developed PCP, while the incidence of PCP in the control group was 8.1% (definite cases 5.5% and probable cases 2.7%). Out of the 49 patients who developed PCP, 10 patients (20.4%) were admitted to the intensive care unit, and the PCP-related death rate was 16.3% (8/49).

Conclusion: This study showed that PCP prophylaxis is highly effective against PCP infection and may help guide prevention of PCP during R-CHOP treatment in DLBCL patients.
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http://dx.doi.org/10.1111/myc.13184DOI Listing
January 2021

Formicolides A and B, Antioxidative and Antiangiogenic 20-Membered Macrolides from a Wood Ant Gut Bacterium.

J Nat Prod 2020 09 5;83(9):2776-2784. Epub 2020 Sep 5.

Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.

Two new macrolides, formicolides A () and B (), were isolated from sp. BA01, a gut bacterial strain of the wood ant (). Their 20-membered macrocyclic lactone structures were established using NMR and mass spectrometric data. The relative configurations of the formicolides were determined by -based configuration analysis utilizing ROESY, HETLOC, and HECADE NMR spectroscopic data. Genomic and bioinformatics analysis of the bacterial strain enabled us to identify the type-I polyketide synthase pathway employing a -acyltransferase system. The absolute configurations of and are proposed based on detailed analysis of the sequences of the ketoreductases in the modular gene cluster and statistical comparative analysis of the experimental NMR chemical shifts and quantum mechanical calculations. Formicolides A and B ( and ) induced quinone reductase activity in murine Hepa-1c1c7 cells and antiangiogenic activity by suppression of tube formation in human umbilical vein endothelial cells.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00772DOI Listing
September 2020

The increased risk of bleeding due to drug-drug interactions in patients administered direct oral anticoagulants.

Thromb Res 2020 11 3;195:243-249. Epub 2020 Aug 3.

Department of Internal Medicine, Seoul National University, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. Electronic address:

Introduction: Direct oral anticoagulants (DOACs) have the potential to increase bleeding due to drug-drug interactions (DDIs). In the present study, the risk of bleeding was evaluated when drugs with potential DDIs were simultaneously prescribed with DOACs.

Materials And Methods: The present study included patients with non-valvular atrial fibrillation (AF) and venous thromboembolism (VTE) who were newly prescribed DOACs between January 2014 and December 2016.

Results: The study included 115,362 patients with AF or VTE who were newly administered DOACs (median age, 73 years, range, 19-108 years; males, 53.0%; AF, 81.9%). A total of 7001 any bleeding (6.1%) and 2283 major bleeding (2.0%) events occurred with DOAC prescriptions. Based on multiple logistic regression analysis, the number of DDIs was significantly associated with bleeding events independent of CHADS-VASc score and Charlson Comorbidity Index (CCI). The rates of exposure to DDI drugs associated with any bleeding and major bleeding were 56.7% and 66.1%, respectively. The most common DDI drugs showed similar distributions in any or major bleeding; non-steroidal anti-inflammatory drugs (NSAIDs), antiplatelet agents, diltiazem, and amiodarone were frequently prescribed.

Conclusions: Physicians prescribing DOACs for AF or VTE should be aware of the increasing risk of bleeding associated with drugs having potential DDIs regardless of comorbidities.
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http://dx.doi.org/10.1016/j.thromres.2020.07.054DOI Listing
November 2020

Association between disability and cardiovascular event and mortality: A nationwide representative longitudinal study in Korea.

PLoS One 2020 30;15(7):e0236665. Epub 2020 Jul 30.

Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

This study aimed to examine the association between disability and cardiovascular (CV) disease incidence and mortality in Korea longitudinally, using a national representative sample. We used the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database, which includes information on the disability of the National Screening Program participants such as severity and type of disability, which were obtained from the Korean National Disability Registry. Cox proportional hazard models were used to evaluate the association between disability and CV disease incidence and mortality. We constructed four models with different levels of adjustment, in which Model 3 was a fully adjusted model. This study included 514,679 participants, and 7,317 CV deaths were reported within a mean follow up of 10.8 ± 3.9 years (maximum, 13.9 years). For 5,572,130 person-year (PY) follow-up, the CV mortality rate was 1.313 per 1,000 PY. In Models 1 and 2, CV disease incidence was significantly higher in participants with disability than in those without disability. In Model 3, the incidence was higher only among participants aged 50-64 years and severe disabled participants aged <50 years. CV mortality was significantly higher in participants with disability than in those without disability in all Models, and the mortality increased in both sexes in Models 1 and 2 but only increased in men in Model 3. Similar results were observed in the subgroup analysis of health behavior and chronic diseases. People with disability showed higher CV disease incidence and mortality than those without disability, regardless of the type of disability or risk factors for CV disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236665PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392251PMC
September 2020

PI3K-targeting strategy using alpelisib to enhance the antitumor effect of paclitaxel in human gastric cancer.

Sci Rep 2020 07 23;10(1):12308. Epub 2020 Jul 23.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173 Beon-gil Bundang-gu, Seongnam, 13620, Republic of Korea.

PIK3CA mutations are frequently observed in various human cancers including gastric cancer (GC). This study was conducted to investigate the anti-tumor effects of alpelisib, a PI3K p110α-specific inhibitor, using preclinical models of GC. In addition, the combined effects of alpelisib and paclitaxel on GC were evaluated. Among the SNU1, SNU16, SNU484, SNU601, SNU638, SNU668, AGS, and MKN1 GC cells, three PIK3CA-mutant cells were predominantly sensitive to alpelisib. Alpelisib monotherapy decreased AKT and S6K1 phosphorylation and induced G/G phase arrest regardless of PIK3CA mutational status. The alpelisib and paclitaxel combination demonstrated synergistic anti-proliferative effects, preferentially on PIK3CA-mutant cells, resulting in increased DNA damage response and apoptosis. In addition, alpelisib and paclitaxel combination potentiated anti-migratory activity in PIK3CA-mutant cells. Alpelisib partially reversed epithelial-mesenchymal transition markers in PIK3CA-mutant cells. In a xenograft model of MKN1 cells, the alpelisib and paclitaxel combination significantly enhanced anti-tumor activity by decreasing Ki-67 expression and increasing apoptosis. Moreover, this combination tended to prolong the survival of tumor-bearing mice. Our data suggest promising anti-tumor efficacy of alpelisib alone or in combination with paclitaxel in PIK3CA-mutant GC cells.
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http://dx.doi.org/10.1038/s41598-020-68998-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378194PMC
July 2020

A short-term, hydroponic-culture of ginseng results in a significant increase in the anti-oxidative activity and bioactive components.

Food Sci Biotechnol 2020 Jul 7;29(7):1007-1012. Epub 2020 Mar 7.

Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, 08826 Republic of Korea.

CA Meyer has a variety of biological effects, including antioxidant and antidiabetic activities. Ginseng requires long-term cultivation, but this can be shortened using hydroponic systems to facilitate the commercial development of ginseng as a functional food. However, the characteristics of short-term-cultured (< 30 days) hydroponic ginseng (sHCG) are unclear. We investigated the characteristics of 21-day-cultured sHCG compared 5-year-old normally cultured ginseng. The free radical-scavenging activity and total ginsenoside and phenolic contents were significantly higher in sHCG than in normally cultured ginseng. Fifteen ginsenosides were detected in sHCG, and the concentrations of most were higher in shoots than roots. These findings suggest that 21-day-cultured sHCG, due to its enhanced antioxidant activity and higher concentrations of total phenolics and ginsenosides (including Rd and Re), has potential as a functional food.
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http://dx.doi.org/10.1007/s10068-020-00735-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297876PMC
July 2020

Apelin-13 Inhibits Methylglyoxal-Induced Unfolded Protein Responses and Endothelial Dysfunction via Regulating AMPK Pathway.

Int J Mol Sci 2020 Jun 6;21(11). Epub 2020 Jun 6.

Department of Pharmacology and Smart-Aging Convergence Research Center, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Korea.

It has been suggested that methylglyoxal (MGO), a glycolytic metabolite, has more detrimental effects on endothelial dysfunction than glucose itself. Recent reports showed that high glucose and MGO induced endoplasmic reticulum (ER) stress and myocyte apoptosis in ischemic heart disease was inhibited by apelin. The goal of the study is to investigate the molecular mechanism by which MGO induces endothelial dysfunction via the regulation of ER stress in endothelial cells, and to examine whether apelin-13, a cytoprotective polypeptide ligand, protects MGO-induced aortic endothelial dysfunction. MGO-induced ER stress and apoptosis were determined by immunoblotting and MTT assay in HUVECs. Aortic endothelial dysfunction was addressed by en face immunostaining and acetylcholine-induced vasodilation analysis with aortic rings from mice treated with MGO in the presence or absence of apelin ex vivo. TUDCA, an inhibitor of ER stress, inhibited MGO-induced apoptosis and reduction of cell viability, suggesting that MGO signaling to endothelial apoptosis is mediated via ER stress, which leads to activation of unfolded protein responses (UPR). In addition, MGO-induced UPR and aortic endothelial dysfunction were significantly diminished by apelin-13. Finally, this study showed that apelin-13 protects MGO-induced UPR and endothelial apoptosis through the AMPK pathway. Apelin-13 reduces MGO-induced UPR and endothelial dysfunction via regulating the AMPK activating pathway, suggesting the therapeutic potential of apelin-13 in diabetic cardiovascular complications.
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http://dx.doi.org/10.3390/ijms21114069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313041PMC
June 2020

Gene expression network analysis of lymph node involvement in colon cancer identifies AHSA2, CDK10, and CWC22 as possible prognostic markers.

Sci Rep 2020 04 28;10(1):7170. Epub 2020 Apr 28.

Department of Pathology, Korea University College of Medicine, Seoul, 02841, Republic of Korea.

Colon cancer has been well studied using a variety of molecular techniques, including whole genome sequencing. However, genetic markers that could be used to predict lymph node (LN) involvement, which is the most important prognostic factor for colon cancer, have not been identified. In the present study, we compared LN(+) and LN(-) colon cancer patients using differential gene expression and network analysis. Colon cancer gene expression data were obtained from the Cancer Genome Atlas and divided into two groups, LN(+) and LN(-). Gene expression networks were constructed using LASSO (Least Absolute Shrinkage and Selection Operator) regression. We identified hub genes, such as APBB1, AHSA2, ZNF767, and JAK2, that were highly differentially expressed. Survival analysis using selected hub genes, such as AHSA2, CDK10, and CWC22, showed that their expression levels were significantly associated with the survival rate of colon cancer patients, which indicates their possible use as prognostic markers. In addition, protein-protein interaction network, GO enrichment, and KEGG pathway analysis were performed with selected hub genes from each group to investigate the regulatory relationships between hub genes and LN involvement in colon cancer; these analyses revealed differences between the LN(-) and LN(+) groups. Our network analysis may help narrow down the search for novel candidate genes for the treatment of colon cancer, in addition to improving our understanding of the biological processes underlying LN involvement. All R implementation codes are available at journal website as Supplementary Materials.
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http://dx.doi.org/10.1038/s41598-020-63806-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189385PMC
April 2020

Clonorchis sinensis secretory protein CsAg17 vaccine induces immune protection.

Parasit Vectors 2020 Apr 25;13(1):215. Epub 2020 Apr 25.

Department of Medical Environmental Biology, Chung-Ang University College of Medicine, Seoul, Republic of Korea.

Background: Clonorchiasis is endemic in East and Southeast Asian countries. For a preventive strategy against infectious diseases, vaccination is the most effective. Here, we evaluated the molecular characteristics and immune responses of CsAg17 protein from Clonorchis sinensis, and investigated its protective effects against C. sinensis challenge.

Methods: A cDNA clone encoding CsAg17 protein and containing a secretory signal peptide at the N-terminus was retrieved from the C. sinensis transcriptome bank. Recombinant CsAg17 B-cell epitope protein and cDNA vaccines were produced and their immune responses were evaluated in FVB mice. The proportional changes of CD3/CD4 and CD3/CD8 T cells were detected by flow cytometry, and immune effectors were measured by ELISA.

Results: The CsAg17 mRNA was transcribed at a higher level in C. sinensis adults than in metacercariae. The CsAg17 protein was distributed in the sperms, oral and ventral suckers, and mesenchymal tissues of C. sinensis adults. In mice challenged with C. sinensis metacercariae, vaccination with CsAg17 protein and cDNA resulted in a reduction to 64% and 69% in worm burden, respectively. Both CsAg17 protein and cDNA vaccines increased the proportion of CD3/CD4 and CD3/CD8 T cells and stimulated the production of Th1 type cytokines such as interleukin (IL)-2, IL-12, and interferon-γ, while maintaining minimum levels of Th2 cytokines. The levels of IgG specific to CsAg17 protein steeply increased in the two vaccinated groups from 2 weeks after immunization. The liver tissue retained good morphology in the mice vaccinated with CsAg17 protein or cDNA, whereas severe inflammation and large serous cysts were observed in the liver of the unvaccinated mice.

Conclusions: Vaccination with CsAg17 protein and cDNA reduced the pathological changes in the bile duct and liver, and ameliorated the worm burden via cellular and humoral immune responses. Thus, they may serve as good vaccine candidates against C. sinensis infections.
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http://dx.doi.org/10.1186/s13071-020-04083-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183723PMC
April 2020

Similar transplant outcomes between haploidentical and unrelated donors after reduced-intensity conditioning with busulfan, fludarabine, and anti-thymocyte globulin in patients with acute leukemia or myelodysplastic syndrome.

Blood Res 2020 Mar 30;55(1):27-34. Epub 2020 Mar 30.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Background: Although T-cell-replete hematopoietic cell transplantation (HCT) from haploidentical donors (HIDs) using anti-thymocyte globulin (ATG) has shown promising outcomes, previous studies often adopted heterogenous graft sources and conditioning.

Methods: We retrospectively compared HCT outcomes from 62 HIDs, 36 partially-matched unrelated donors (PUDs), and 55 matched unrelated donors (MUDs) in patients with acute leukemia or myelodysplastic syndrome using the same graft source of peripheral blood and a reduced intensity conditioning of busulfan, fludarabine, and ATG.

Results: The estimates of 3-yr disease-free survival (DFS) and overall survival (OS) rates were not significantly different among the MUD, HID, and PUD groups, at 46%, "41%, and 36%" for the DFS rate (=0.844), and 55%, 45%, and 45% for the OS rate (=0.802), respectively. Cumulative incidence of relapse and non-relapse mortality at 3 yr was similar among different donor types. Subsequent multivariable analyses showed that the sex of the patient (male) and a high/very high disease risk index were independently associated with poorer DFS and OS, while the donor type was not.

Conclusion: T-cell replete HCT from HIDs using an ATG-containing reduced intensity conditioning regimen may be a reasonable option in the absence of matched related donors in patients with acute leukemia or myelodysplastic syndrome.
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http://dx.doi.org/10.5045/br.2020.55.1.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106115PMC
March 2020

Cancer cell‑specific anticancer effects of Coptis chinensis on gefitinib‑resistant lung cancer cells are mediated through the suppression of Mcl‑1 and Bcl‑2.

Int J Oncol 2020 06 24;56(6):1540-1550. Epub 2020 Mar 24.

Department of Pathology, Korea University College of Medicine, Seoul 02841, Republic of Korea.

The epidermal growth factor receptor (EGFR)‑tyrosine kinase inhibitor (TKI), gefitinib, is an effective therapeutic drug used in the treatment of non‑small cell lung cancers (NSCLCs) harboring EGFR mutations. However, acquired resistance significantly limits the efficacy of EGFR‑TKIs and consequently, the current chemotherapeutic strategies for NSCLCs. It is, therefore, necessary to overcome this resistance. In the present study, the anticancer potential of natural extracts of Coptis chinensis (ECC) against gefitinib‑resistant (GR) NSCLC cells were investigated in vitro and in vivo. ECC inhibited the viability, migration and invasion, and effectively induced the apoptosis of GR cells. These effects were associated with the suppression of EGFR/AKT signaling and the expression of anti‑apoptotic proteins, Mcl‑1 and Bcl‑2, which were overexpressed in GR NSCLC cells. Combination treatment with ECC and gefitinib enhanced the sensitivity of GR cells to gefitinib in vitro, but not in vivo. However, ECC increased the survival of individual zebrafish without affecting the anticancer effect to cancer cells in vivo, which indicated a specific cytotoxic effect of ECC on cancer cells, but not on normal cells; this is an important property for the development of novel anticancer drugs. On the whole, the findings of the present study indicate the potential of ECC for use in the treatment of NSCLC, particularly in combination with EGFR‑TKI therapy, in EGFR‑TKI‑resistant cancers.
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http://dx.doi.org/10.3892/ijo.2020.5025DOI Listing
June 2020

System reliability analysis of the scoliosis disorder.

BMC Musculoskelet Disord 2020 Mar 31;21(1):199. Epub 2020 Mar 31.

Department of Civil and Environmental Engineering, Washington State University, Pullman, USA.

Background: Scoliosis is a spine abnormal deviation, which is an idiopathic disorder among children and adolescents. As a matter of the fact, distribution of loads on the patient's spine and load-carrying capacity of the vertebral column are both random variables. Therefore, the probabilistic approach may consider as a sophisticated method to deal with this problem.

Method: Reliability analysis is a probabilistic-based approach to consider the uncertainties of load and resistance of the vertebral column. The main contribution of this paper is to compare the reliability level of a normal and scoliosis spinal. To do so, the numerical analyses associated with the inherent random parameters of bones and applied load are performed. Then, the reliability indices for all vertebrae and discs are determined. Accordingly, as the main innovation of this paper, the system reliability indices of the spinal column for both normal and damaged backbone systems are represented.

Results: Based on the required reliability index for normal spinal curvature the target system reliability level for scoliosis disorder is proposed.

Conclusion: Since the proposed target reliability index is based on the strength limit state of the vertebral column, it can be considered as a reliability level for any proposed treatment approaches.
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http://dx.doi.org/10.1186/s12891-020-03230-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110658PMC
March 2020
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