• Clinical and Experimental Pediatrics
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• 제64권7호
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• pp.355-363
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• 2021

Background: Nephrotic syndrome (NS) is a common renal disorder in children attributed to podocyte injury. However, children with the same diagnosis have markedly variable treatment responses, clinical courses, and outcomes, suggesting molecular heterogeneity. Purpose: This study aimed to explore the molecular responses of podocytes to nephrotic plasma to identify specific genes and signaling pathways differentiating various clinical NS groups as well as biological processes that drive injury in normal podocytes. Methods: Transcriptome profiles from immortalized human podocyte cell line exposed to the plasma of 8 subjects (steroid-sensitive nephrotic syndrome [SSNS], n=4; steroid-resistant nephrotic syndrome [SRNS], n=2; and healthy adult individuals [control], n=2) were generated using microarray analysis. Results: Unsupervised hierarchical clustering of global gene expression data was broadly correlated with the clinical classification of NS. Differential gene expression (DGE) analysis of diseased groups (SSNS or SRNS) versus healthy controls identified 105 genes (58 up-regulated, 47 down-regulated) in SSNS and 139 genes (78 up-regulated, 61 down-regulated) in SRNS with 55 common to SSNS and SRNS, while the rest were unique (50 in SSNS, 84 genes in SRNS). Pathway analysis of the significant (P≤0.05, -1≤ log2 FC ≥1) differentially expressed genes identified the transforming growth factor-β and Janus kinase-signal transducer and activator of transcription pathways to be involved in both SSNS and SRNS. DGE analysis of SSNS versus SRNS identified 2,350 genes with values of P≤0.05, and a heatmap of corresponding expression values of these genes in each subject showed clear differences in SSNS and SRNS. Conclusion: Our study observations indicate that, although podocyte injury follows similar pathways in different clinical subgroups, the pathways are modulated differently as evidenced by the heatmap. Such transcriptome profiling with a larger cohort can stratify patients into intrinsic subtypes and provide insight into the molecular mechanisms of podocyte injury.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2019년도 추계학술대회
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• pp.8-8
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• 2019

The stringent response (SR) is characterized as a bacterial defense mechanism in response to various growth-inhibiting stresses. It is activated by accumulation of a small nucleotide regulator, (p)ppGpp, and induces global changes in bacterial transcription and translation. Recent work from our group has shown that (p)ppGpp plays a critical role in virulence and survival in Vibrio cholerae. The genes, relA and relV, are involved in the production of (p)ppGpp, while the spoT gene encodes an enzyme that hydrolyzes it in V. cholerae. A mutant strain defective in (p)ppGpp production (i.e. ${\Delta}relA{\Delta}relV{\Delta}spoT$ mutant) lost the ability to produce cholera toxin (CT) and lost their viability due to uncontrolled production of organic acids, when grown with extra glucose. In contrast, the ${\Delta}relA{\Delta}spoT$ mutant, a (p)ppGpp overproducer strain, produced enhanced level of CT and exhibited better growth in glucose supplemented media via glucose metabolic switch from organic fermentation to acetoin, a neutral fermentation end product, fermentation. These findings indicates that (p)ppGpp, in addition to its well-known role as a SR mediator, positively regulates CT production and maintenance of growth fitness in V. cholerae. This implicates SR as a promising drug target, inhibition of which may possibly downregulate V. cholerae virulence and survival fitness. Therefore, we screened a chemical library and identified a compound that induces medium acidification (termed iMAC) and thereby loss of wild type V. cholerae viability under glucose-rich conditions. Further, we present a potential mechanism by which the compound inhibits (p)ppGpp accumulation. Together, these results indicate that iMAC treatment causes V. cholerae cells to produce significantly less (p)ppGpp, an important regulator of the bacterial virulence and survival response, and further suggesting that it has a therapeutic potential to be developed as a novel antibacterial agent against cholera.

• 한국멀티미디어학회논문지
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• 제24권5호
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• pp.684-694
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• 2021

Resting-state Functional Magnetic Resonance Imaging(fMRI) data detects the temporal correlations in Blood Oxygen Level Dependent(BOLD) signal and these temporal correlations are regarded to reflect intrinsic cortical connectivity, which is deactivated during attention demanding, non-self referential tasks, called Default Mode Network(DMN). The relationship between fMRI and anatomical connectivity has not been studied in detail, however, the preceded studies have tried to clarify this relationship using Diffusion Tensor Imaging(DTI) and fMRI. These studies use method that fMRI data assists DTI data or vice versa and it is used as guider to perform DTI tractography on the brain image. In this study, we hypothesized that functional connectivity in resting state would reflect anatomical connectivity of DMN and the combined images include information of fMRI and DTI showed visible connection between brain regions related in DMN. In the previous study, functional connectivity was determined by subjective region of interest method. However, in this study, functional connectivity was determined by objective and advanced method through Independent Component Analysis. There was a stronger connection between Posterior Congulate Cortex(PCC) and PHG(Parahippocampa Gyrus) than Anterior Cingulate Cortex(ACC) and PCC. This technique might be used in several clinical field and will be the basis for future studies related to aging and the brain diseases, which are needed to be translated not only functional connectivity, but structural connectivity.

• 대한의용생체공학회:의공학회지
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• 제42권3호
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• pp.80-85
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• 2021

We developed a model to classify the absence of cervical cancer using deep learning from the cervical image to which the histogram equalization algorithm was applied, and to compare the performance of each model. A total of 4259 images were used for this study, of which 1852 images were normal and 2407 were abnormal. And this paper applied Image Sharpening(IS), Histogram Equalization(HE), and Contrast Limited Adaptive Histogram Equalization(CLAHE) to the original image. Peak Signal-to-Noise Ratio(PSNR) and Structural Similarity index for Measuring image quality(SSIM) were used to assess the quality of images objectively. As a result of assessment, IS showed 81.75dB of PSNR and 0.96 of SSIM, showing the best image quality. CLAHE and HE showed the PSNR of 62.67dB and 62.60dB respectively, while SSIM of CLAHE was shown as 0.86, which is closer to 1 than HE of 0.75. Using ResNet-50 model with transfer learning, digital image-processed images are classified into normal and abnormal each. In conclusion, the classification accuracy of each model is as follows. 90.77% for IS, which shows the highest, 90.26% for CLAHE and 87.60% for HE. As this study shows, applying proper digital image processing which is for cervical images to Computer Aided Diagnosis(CAD) can help both screening and diagnosing.

• International Journal of Oral Biology
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• 제45권4호
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• pp.169-178
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• 2020

L-ascorbic acid (L-AA; vitamin C) induces apoptosis in cancer cells. This study aimed to elucidate the molecular mechanisms of L-AA-induced apoptosis in human laryngeal epidermoid carcinoma Hep-2 cells. L-AA suppressed the viability of Hep-2 cells and induced apoptosis, as shown by the cleavage and condensation of nuclear chromatin and increased number of Annexin V-positive cells. L-AA decreased Bcl-2 protein expression but upregulated Bax protein levels. In addition, cytochrome c release from the mitochondria into the cytosol and activation of caspase-9, -8, and -3 were enhanced by L-AA treatment. Furthermore, apoptosis-inducing factor (AIF) and endonuclease G (EndoG) were translocated into the nucleus during apoptosis of L-AA-treated Hep-2 cells. L-AA effectively inhibited the constitutive nuclear factor-κB (NF-κB) activation and attenuated the nuclear expression of the p65 subunit of NF-κB. Interestingly, L-AA treatment of Hep-2 cells markedly activated Akt and mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase [JNK]) and and LY294002 (Akt inhibitor), SB203580 (p38 inhibitor) or SP600125 (a JNK inhibitor) decreased the levels of Annexin V-positive cells. These results suggested that L-AA induces the apoptosis of Hep-2 cells via the nuclear translocation of AIF and EndoG by modulating the Bcl-2 family and MAPK/Akt signaling pathways.

• 대한의용생체공학회:의공학회지
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• 제43권2호
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• pp.124-130
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• 2022

In this paper, we proposed a portable electronic cardiogram and stethoscope (ECGS) that can simultaneously perform the electrocardiogram (ECG) and auscultation tests to increase the reliability of diagnosis of heart disease. To measure the ECG and heart sound (HS) at the same time, three ECG electrodes and a microphone sensor were combined into a triangular shape with a width of 90 mm and a height of 97 mm that can be held in one hand. In order to prevent skin problems when they contact the patient's skin, a capacitive coupled electrode was selected as the ECG electrode and a silicone material was used in a chest piece with the microphone sensor. For the signals measured from the electrodes and the chest piece, filters were respectively configured to pass only the signals of 0.01-100 Hz and 20-250 Hz, which are frequency bands for ECG and HS. The filtered ECG and HS analog signals were converted into digital signals and transmitted to a PC using wireless communication for monitoring them. The HS could be auscultated simultaneously using an earphone. The monitored ECG had an SNR of about 34 dB and a P-QRS-T waveform is clearly visible. In addition, the HS had an SNR of about 28 dB and both S₁ and S₂ are clearly visible. It is expected that it can aid doctors' inexperience in analyzing the ECG and HS.

• 대한의용생체공학회:의공학회지
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• 제44권1호
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• pp.80-84
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• 2023

Electrodes are one of the types of biosensors capable of measuring bio signals, such as electrocardiogram (ECG) and electromyogram (EMG) signals. These electrodes are used in various fields and offer the advantage of being able to measure ECG signals without the need for skin attachment, compared to Ag/AgCl electrodes. The purpose of this study was to evaluate the efficacy of conductive textile electrodes in collecting ECG signals in a bed-like environment. Three adult participants were involved, and a total of 30 minutes of ECG signals were collected for each participant. The collected ECG signals were analyzed to determine the heart rate, normLF and a comparison was made between the conductive textile electrodes and Ag/AgCl electrodes. As a result, the change in heart rate and normLF could be observed, and in particular, the difference between the two electrodes decreased. This study confirmed that conductive textile electrodes can effectively collect ECG signals in a bed-like environment. It is hoped that this research will lead to the development of a system that can detect various sleep-related diseases through the use of these electrodes.

• 한국응용곤충학회지
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• 제61권1호
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• pp.15-28
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• 2022

신경펩타이드(Neuropeptide)는 신경세포에서 분비되는 단백질성 물질로, 곤충 호르몬에서 가장 큰 그룹으로 차지한다. 이들은 곤충의 전 생육단계에 걸쳐 지방체의 항상성, 섭식, 소화, 배설, 순환, 번식, 탈피/변태 등 다양한 생리적 기능과 행동을 조절하는데 관여하고 있다. 신경호르몬 일종인 PRXamide (NH₂) 펩타이드 계열 호르몬은 카르복실기 끝에 PRX (X, 다양한 아미노산)라는 공통의 아미노산 서열이 특징적으로 존재하고 있으며, 곤충 전반에 걸쳐 발견된다. 곤충에서PRX 신경호르몬은 다양한 생물학적 기능에 관련하고 있는데 호르몬구조와 기능에 따라 크게 3가지로 분류한다. Pyrokinin (PK)계열의 호르몬은 페로몬 생합성 활성화 신경펩타이드(pheromone biosynthesis activating neuropeptide, PBAN) 및 휴면 호르몬(diapause hormone, DH)이 속하며, 카파(CAPA) 펩타이드 호르몬, 그리고 탈피촉진 호르몬(ecdysis trigging hormone, ETH)이 여기에 속한다. PK 계열의 PBAN 호르몬은 지금으로부터 약 30년전 나방에서 처음 밝혀졌으며, 성페로몬 생합성을 자극하는 신경호르몬으로 확인되었다. 그 이후, PBAN의 연구는 절지동물 전반에 걸쳐 다양한 연구자들에 의하여 광범위하게 이루어졌다. 본 종설은 PBAN의 유전자 구조와 발현, PBAN에 의한 세포신호 전달과 성페로몬 생합성에 관련된 생리적 기작, 그리고 신경호르몬과 PBAN을 이용한 새로운 해충 방제법 개발의 가능성과 예를 소개한다.

• Journal of Microbiology and Biotechnology
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• 제32권12호
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• pp.1589-1598
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• 2022

Microfibrillated cellulose (MFC) is a valuable material with wide industrial applications, particularly for the food and cosmetics industries, owing to its excellent physiochemical properties. Here, we prepared high-solid microfibrillated cellulose (HMFC) from the centrifugation of Gelidium amansiiderived MFC right after fibrillation. Dispersion properties, morphology, and structural changes were monitored during processing. HMFC has a five-fold higher solid concentration than MFC without significant changes to dispersion properties. SEM images and FTIR spectra of HMFC revealed a stable surface and structure against centrifugal forces. HMFC exhibited 2,2'-azino-bis (3-ethylbenzothiazoline6-sulfonic acid) (ABTS) radical scavenging activity, although it could not scavenge 2,2-diphenyl-1- picrylhydrazyl (DPPH). Moreover, HMFC inhibited the generation of LPS-induced excessive nitrite and radial oxygen species in murine macrophage RAW264.7 cells. Additionally, HMFC suppressed LPS-induced Keap-1 expression in the cytosol but did not alter iNOS expression. HMFC also attenuated the UVB-induced phosphorylation of p38, c-Jun N-terminal kinase (JNK) 1/2, and extracellular-signal-regulated kinase (ERK) 1/2, as well as the phosphorylation of c-Jun in the immortalized human skin keratinocyte HaCaT cells. Therefore, the application of centrifugation is suitable for producing high-solid MFC as a candidate material for anti-inflammatory and antioxidative marine cosmeceuticals.

• Biomolecules & Therapeutics
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• 제31권2호
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• pp.200-209
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• 2023

Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) amplification or sensitive mutations initially respond to the tyrosine kinase inhibitor gefitinib, however, the treatment becomes less effective over time by resistance mechanism including mesenchymal-epithelial transition (MET) overexpression. A therapeutic strategy targeting MET and EGFR may be a means to overcoming resistance to gefitinib. In the present study, we found that picropodophyllotoxin (PPT), derived from the roots of Podophyllum hexandrum, inhibited both EGFR and MET in NSCLC cells. The antitumor efficacy of PPT in gefitinib-resistant NSCLC cells (HCC827GR), was confirmed by suppression of cell proliferation and anchorage-independent colony growth. In the targeting of EGFR and MET, PPT bound with EGFR and MET, ex vivo, and blocked both kinases activity. The binding sites between PPT and EGFR or MET in the computational docking model were predicted at Gly772/Met769 and Arg1086/Tyr1230 of each ATP-binding pocket, respectively. PPT treatment of HCC827GR cells increased the number of annexin V-positive and subG1 cells. PPT also caused G2/M cell-cycle arrest together with related protein regulation. The inhibition of EGFR and MET by PPT treatment led to decreases in the phosphorylation of the downstream-proteins, AKT and ERK. In addition, PPT induced reactive oxygen species (ROS) production and GRP78, CHOP, DR5, and DR4 expression, mitochondrial dysfunction, and regulated involving signal-proteins. Taken together, PPT alleviated gefitinib-resistant NSCLC cell growth and induced apoptosis by reducing EGFR and MET activity. Therefore, our results suggest that PPT can be a promising therapeutic agent for gefitinib-resistant NSCLC.