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1.
Anim Biosci ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38938028

ABSTRACT

Objective: The improvement of carcass traits is essential for the Hanwoo industry because of the Hanwoo grade determination system, and Genome-Wide Association Study (GWAS) analysis is an instrumental tool for identifying the genetic factors that impact these traits. While GWAS analysis utilizing family data offers advantages in minimizing genetic bias, research on family-based GWAS in Hanwoo is currently lacking. Methods: This study classified Group A using both parental and offspring genetic information, and Group B based solely on offspring genetic information, to compare GWAS analysis results of Hanwoo carcass traits. Results: 16 significant SNP markers (carcass weight (CWT) 7, back fat thickness (BFT) 3, marbling score (MS) 6) were identified in Group A, and 7 significant SNP markers (CWT 3, eye muscle area (EMA) 1, BFT 1, MS 2) were identified in Group B. Functional annotation analysis revealed only one common function related to carcass traits between the groups, while Protein-protein interaction (PPI) analysis indicated more gene interactions in Group A. The reliability of estimated values for common SNP markers identified between the groups was higher in Group A. Conclusion: GWAS analysis utilizing parental genetic information holds greater potential for application, owing to its higher reliability of estimated values and the ability to explore numerous candidate genes.

2.
Med Eng Phys ; 119: 104035, 2023 09.
Article in English | MEDLINE | ID: mdl-37634912

ABSTRACT

Despite several theories have been proposed to explain the progression of Adolescent Idiopathic Scoliosis (AIS), there is no consensus on the mechanical factors that control the spinal deformities. Prominent biomechanical notions focus on the geometrical asymmetry and differential growth, however, the correlation between these phenomena remains unclear. We postulate that intradiscal pressure and its connection with the supporting ligamentous structures are the reasons behind the asymmetric growth in AIS. To investigate this hypothesis, a numerical 3D patient-specific model of a scoliotic spine is constructed to carry upper body weight. Four analyses are performed: control simulation with no ligaments followed by 3 simulations, in each, a different and stiffer set of ligaments is employed. The analyses showed that intradiscal pressure is relatively high in the spine's higher-deformity region. Moreover, the stiffness effect of the ligamentous tethering correlated directly to intradiscal pressure; the stiffer the ligaments, the higher the intradiscal pressure. Due to geometrical asymmetry, the pressure is eccentric toward the concave region of deformed vertebral units. As a result, the deformed annulus fibrosus generated uplifts in the convex side of deformed vertebral units. The eccentric pressure and the uplift are opposite in location and direction creating an imbalanced mechanical environment for the spine during growth.


Subject(s)
Ligaments , Spine , Adolescent , Humans , Computer Simulation
3.
Anim Biosci ; 36(9): 1327-1335, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37170517

ABSTRACT

OBJECTIVE: When evaluating individuals with the same parent and no phenotype by pedigree best linear unbiased prediction (BLUP), it is difficult to explain carcass grade difference and select individuals because they have the same value in pedigree BLUP (PBLUP). However, single step GBLUP (ssGBLUP), which can estimate the breeding value suitable for the individual by adding genotype, is more accurate than the existing method. METHODS: The breeding value and accuracy were estimated with pedigree BLUP and ssGBLUP using pedigree and genotype of 408 Hanwoo cattle from 16 families with the same parent among siblings produced by fertilized egg transplantation. A total of 14,225 Hanwoo cattle with pedigree, genotype and phenotype were used as the reference population. PBLUP obtained estimated breeding value (EBV) using the pedigree of the test and reference populations, and ssGBLUP obtained genomic EBV (GEBV) after constructing and H-matrix by integrating the pedigree and genotype of the test and reference populations. RESULTS: For all traits, the accuracy of GEBV using ssGBLUP is 0.18 to 0.20 higher than the accuracy of EBV obtained with PBLUP. Comparison of EBV and GEBV of individuals without phenotype, since the value of EBV is estimated based on expected values of alleles passed down from common ancestors. It does not take Mendelian sampling into consideration, so the EBV of all individuals within the same family is estimated to be the same value. However, GEBV makes estimating true kinship coefficient based on different genotypes of individuals possible, so GEBV that corresponds to each individual is estimated rather than a uniform GEBV for each individual. CONCLUSION: Since Hanwoo cows bred through embryo transfer have a high possibility of having the same parent, if ssGBLUP after adding genotype is used, estimating true kinship coefficient corresponding to each individual becomes possible, allowing for more accurate estimation of breeding value.

4.
Neurobiol Dis ; 168: 105692, 2022 06 15.
Article in English | MEDLINE | ID: mdl-35306174

ABSTRACT

Electrophysiological biomarkers reflecting the pathological activities in the basal ganglia are essential to gain an etiological understanding of Parkinson's disease (PD) and develop a method of diagnosing and treating the disease. Previous studies that explored electrophysiological biomarkers in PD have focused mainly on oscillatory or periodic activities such as beta and gamma oscillations. Emerging evidence has suggested that the nonoscillatory, aperiodic component reflects the firing rate and synaptic current changes corresponding to cognitive and pathological states. Nevertheless, it has never been thoroughly examined whether the aperiodic component can be used as a biomarker that reflects pathological activities in the basal ganglia in PD. In this study, we examined the parameters of the aperiodic component in hemiparkinsonian rats and tested its practicality as an electrophysiological biomarker of pathological activity. We found that a set of aperiodic parameters, aperiodic offset and exponent, were significantly decreased by the nigrostriatal lesion. To further prove the usefulness of the parameters as biomarkers, acute levodopa treatment reverted the aperiodic offset. We then compared the aperiodic parameters with a previously established periodic biomarker of PD, beta frequency oscillation. We found a significantly low negative correlation with beta power. We showed that the performance of the machine learning-based prediction of pathological activities in the basal ganglia can be improved by using both beta power and the aperiodic component, which showed a low correlation with each other. We suggest that the aperiodic component will provide a more sensitive measurement to early diagnosis PD and have the potential to use as the feedback parameter for the adaptive deep brain stimulation.


Subject(s)
Deep Brain Stimulation , Parkinson Disease , Animals , Basal Ganglia , Biomarkers , Deep Brain Stimulation/methods , Dopamine , Levodopa/pharmacology , Levodopa/therapeutic use , Rats
5.
J Anim Breed Genet ; 139(3): 281-291, 2022 May.
Article in English | MEDLINE | ID: mdl-34902178

ABSTRACT

The genetic improvement of Hanwoo is dependent on the estimated breeding value (EBV) of pedigree-based Korean proven bull's number, and the genetic evaluation for cows is difficult due to insufficient pedigree and test records. Genomic selection involves utilizing the individual's genotype to estimate the breeding value (BV) and is determined to be an appropriate evaluation method for cows who lack test information. This study used pedigree and genotype to estimate and analyse BV and accuracy of Hanwoo cows in the Gyeongnam area using pedigree best linear unbiased prediction (PBLUP) and genomic best linear unbiased prediction (GBLUP). The test group acquired pedigree and genotype of 919 Hanwoo cows in the Gyeongnam area. The traits used for analysis were carcass weight (CWT), eye muscle areas (EMA), backfat thickness (BFT) and marbling score (MS). PBLUP used Reference group 1 containing the pedigree and phenotype of 919 Hanwoo cows and 545,483 heads to construct the numeric relationship matrix and estimated the EBV and accuracy. GBLUP used Reference group 2 containing the genotype and phenotype of 919 Hanwoo cows and 17,226 heads to construct the genomic relationship matrix and estimated the genomic EBV (GEBV) and accuracy. In the order of CWT, EMA, BFT and MS, the accuracy of PBLUP was 0.488, 0.480, 0.482 and 0.486 while the accuracy of GBLUP was higher with 0.779, 0.758, 0.766 and 0.791. And for 104 cows without relationship coefficient on pedigree to the reference group, the accuracy as PBLUP was estimated to be 0, but for GBLUP, it was possible to estimate the accuracy for all individuals. If GBLUP is applied to cows raised in general farms, the genetic evaluation can be performed even on animals without pedigree and high-accuracy estimation, enabling selection of excellent cows. Accordingly, by securing the genetic diversity of cows, it is expected to increase the profitability of farms by decreasing the inbreeding rate and increasing efficiency of elite calf production.


Subject(s)
Genome , Genomics , Animals , Cattle/genetics , Female , Genomics/methods , Genotype , Male , Models, Genetic , Pedigree , Phenotype , Republic of Korea
6.
Biomed Opt Express ; 12(11): 7199-7222, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34858710

ABSTRACT

Detecting Alzheimer's disease (AD) is an important step in preventing pathological brain damage. Working memory (WM)-related network modulation can be a pathological feature of AD, but is usually modulated by untargeted cognitive processes and individual variance, resulting in the concealment of this key information. Therefore, in this study, we comprehensively investigated a new neuromarker, named "refined network," in a prefrontal cortex (PFC) that revealed the pathological features of AD. A refined network was acquired by removing unnecessary variance from the WM-related network. By using a functional near-infrared spectroscopy (fNIRS) device, we evaluated the reliability of the refined network, which was identified from the three groups classified by AD progression: healthy people (N=31), mild cognitive impairment (N=11), and patients with AD (N=18). As a result, we identified edges with significant correlations between cognitive functions and groups in the dorsolateral PFC. Moreover, the refined network achieved a significantly correlating metric with neuropsychological test scores, and a remarkable three-class classification accuracy (95.0%). These results implicate the refined PFC WM-related network as a powerful neuromarker for AD screening.

7.
Article in English | MEDLINE | ID: mdl-34639857

ABSTRACT

This study investigates age and cultural differences in the negative effects of senders' wearing masks on receivers' readabilities of senders' facially expressed emotions in interpersonal interactions. An online experiment was thus conducted with Koreans and Americans aged over 20 years. Based on sampling quotas by nationality, age group and gender, Korean (n = 240) and American (n = 273) participants were recruited from panel members of a Korean research company and Amazon's Mechanical Turk via email and the website, respectively. The participants played receiver roles to infer senders' facially expressed emotions presented in photos in the experiment. They judged emotions facially expressed by the senders without masks and with masks are shown in photos. The results revealed that the senders' wearing masks reduced the readabilities of the senders' facially expressed anger among participants aged 30-49 years more than among participants aged 20-29 years. The senders' wearing masks decreased the readabilities of the senders' facially expressed fear for participants in their 50's more than for participants in their 20's. When the senders wore masks, the readabilities of the senders' facially expressed happiness dropped among participants aged over 60 years more than among participants aged 20-49 years. When senders wore masks, American participants' readabilities of disgust, fear, sadness and happiness expressed in the senders' faces declined more than Korean participants' readabilities of those emotions. The implications and limitations of these findings are discussed.


Subject(s)
Emotions , Facial Expression , Anger , Humans , Recognition, Psychology , Republic of Korea , United States
8.
J Alzheimers Dis ; 84(1): 377-392, 2021.
Article in English | MEDLINE | ID: mdl-34569962

ABSTRACT

BACKGROUND: The coexistence of magnetite within protein aggregates in the brain is a typical pathologic feature of Alzheimer's disease (AD), and the formation of amyloid-ß (Aß) plaques induces critical impairment of cognitive function. OBJECTIVE: This study aimed to investigate the therapeutic effect of proton stimulation (PS) targeting plaque magnetite in the transgenic AD mouse brain. METHODS: A proton transmission beam was applied to the whole mouse brain at a single entrance dose of 2 or 4 Gy to test the effect of disruption of magnetite-containing Aß plaques by electron emission from magnetite. The reduction in Aß plaque burden and the cognitive function of the PS-treated mouse group were assayed by histochemical analysis and memory tests, respectively. Aß-magnetite and Aß fibrils were treated with PS to investigate the breakdown of the amyloid protein matrix. RESULTS: Single PS induced a 48-87%reduction in both the amyloid plaque burden and ferrous-containing magnetite level in the early-onset AD mouse brain while saving normal tissue. The overall Aß plaque burden (68-82%) and (94-97%) hippocampal magnetite levels were reduced in late onset AD mice that showed improvements in cognitive function after PS compared with untreated AD mice (p < 0.001). Analysis of amyloid fibrils after exposure to a single 2 or 4 Gy proton transmission beam demonstrated that the protein matrix was broken down only in magnetite-associated Aß fibrils. CONCLUSION: Single PS targeting plaque magnetite effectively decreases the amyloid plaque burden and the ferrous-containing magnetite level, and this effect is useful for memory recovery.


Subject(s)
Alzheimer Disease , Ferrosoferric Oxide/metabolism , Iron/toxicity , Memory/physiology , Oxidation-Reduction , Plaque, Amyloid/pathology , Alzheimer Disease/pathology , Alzheimer Disease/radiotherapy , Animals , Brain/pathology , Disease Models, Animal , Female , Humans , Mice , Mice, Transgenic , Proton Therapy
9.
Sensors (Basel) ; 21(10)2021 May 12.
Article in English | MEDLINE | ID: mdl-34066116

ABSTRACT

Distributed optical fiber sensors are a promising technology for monitoring the structural health of large-scale structures. The fiber sensors are usually coated with nonfragile materials to protect the sensor and are bonded onto the structure using adhesive materials. However, local deformation of the relatively soft coating and adhesive layers hinders strain transfer from the base structure to the optical fiber sensor, which reduces and distorts its strain distribution. In this study, we analytically derive a strain transfer function in terms of strain periods, which enables us to understand how the strain reduces and is distorted in the optical fiber depending on the variation of the strain field. We also propose a method for back-calculating the base structure's strain field using the reduced and distorted strain distribution in the optical fiber sensor. We numerically demonstrate the back-calculation of the base strain using a composite beam model with an open hole and an attached distributed optical fiber sensor. The new strain transfer function and the proposed back-calculation method can enhance the strain field estimation accuracy in using a distributed optical fiber sensor. This enables us to use a highly durable distributed optical fiber sensor with thick protective layers in precision measurement.

10.
Cancers (Basel) ; 12(5)2020 Apr 30.
Article in English | MEDLINE | ID: mdl-32365904

ABSTRACT

Low-dose irradiation (LDI) has recently been shown to have various beneficial effects on human health, such as on cellular metabolic activities, DNA repair, antioxidant activity, homeostasis potency, and immune activation. Although studies on the immunogenic effects of LDI are rapidly accumulating, clinical trials for cancer treatment are considered premature owing to the lack of available preclinical results and protocols. Here, we aim to investigate anti-tumor and anti-metastatic effects of whole-body LDI in several tumor-bearing mouse models. Mice were exposed to single or fractionated whole-body LDI prior to tumor transplantation, and tumor growth and metastatic potential were determined, along with analysis of immune cell populations and expression of epithelial-mesenchymal transition (EMT) markers. Whole-body fractionated-LDI decreased tumor development and lung metastasis not only by infiltration of CD4+, CD8+ T-cells, and dendritic cells (DCs) but also by attenuating EMT. Moreover, a combination of whole-body LDI with localized high-dose radiation therapy reduced the non-irradiated abscopal tumor growth and increased infiltration of effector T cells and DCs. Therefore, whole-body LDI in combination with high-dose radiation therapy could be a potential therapeutic strategy for treating cancer.

11.
Cancers (Basel) ; 12(5)2020 May 11.
Article in English | MEDLINE | ID: mdl-32403237

ABSTRACT

BACKGROUNDS: Radioimmunotherapy (RIT) serves as a targeted therapy for non-Hodgkin lymphomas (NHL). Although HIF(Hypoxia-inducible factors)-1α is an important biomarker during radiation therapy, its role in NHL is unclear. Atorvastatin (ATV) is used as a combination drug for chemotherapy. METHODS: We investigated whether ATV downregulated tumor radio-resistance and enhanced the anticancer effect of 131I-RTX (rituximab) in Raji xenograft mouse models. First, the increased uptake and enhanced therapeutic effect of 131I-RTX by ATV was confirmed using molecular imaging in Raji xenograft subcutaneous model and orthotropic model with SPECT and IVIS images. Second, we examined the profile of differentially expressed miRNAs using miRNA array. RESULTS: We found that miR-346 inhibited HIF-1α/VEGF (Vascular endothelial growth factor) during ATV combination therapy with 131I-RTX. The underlying mechanism of ATV involved induction of anti-angiogenesis and radiosensitivity by downregulating HIF-1α in Raji cells. CONCLUSION: Our findings suggested that combination therapy with ATV and 131I-RTX is a promising strategy for enhancing the potency of 131I-RTX therapy in poorly responding patients and those with radio-resistance.

12.
FASEB J ; 34(6): 8102-8113, 2020 06.
Article in English | MEDLINE | ID: mdl-32297663

ABSTRACT

DNA double-strand breaks (DSBs) are one of the most serious types of DNA damage. However, multiple repair pathways are present in cells to ensure rapid and appropriate repair of DSBs. Pathway selection depends on several factors including cell type, cell cycle phase, and damage severity. Ribosomal protein S3 (rpS3), a component of the 40S small ribosomal subunit, is a multi-functional protein primarily involved in protein synthesis. rpS3 is also involved in the mediation of various extra-ribosomal pathways, including DNA damage processing and the stress response. Here, we report that rpS3 is a novel negative regulator of non-homologous end joining (NHEJ)-mediated repair of DSBs. We found that rpS3 interacts with the Ku heterodimers of the DNA-dependent protein kinase (DNA-PK) complex and slows down NHEJ ligation reactions, ultimately triggering p53-dependent cell death following treatment with high-dose ionizing radiation. After DSB formation, DNA-PK phosphorylates rpS3, which consequently reduces the binding of rpS3 to the Ku complex. We hypothesized that rpS3 may play a role in DSB repair by repressing NHEJ, while inducing other repair pathways, and by initiating DSB-induced cell death in response to severe DNA damage.


Subject(s)
DNA Damage/genetics , DNA End-Joining Repair/genetics , DNA/metabolism , Ribosomal Proteins/metabolism , Cell Line, Tumor , DNA Breaks, Double-Stranded , DNA-Activated Protein Kinase/metabolism , DNA-Binding Proteins/metabolism , Humans
13.
Biomed Opt Express ; 11(4): 1725-1741, 2020 Apr 01.
Article in English | MEDLINE | ID: mdl-32341843

ABSTRACT

Cognitive decline (CD) is a major symptom of mild cognitive impairment (MCI). Patients with MCI have an increased likelihood of developing Alzheimer's disease (AD). Although a cure for AD is currently lacking, medication therapies and/or daily training in the early stage can alleviate disease progression and improve patients' quality of life. Accordingly, investigating CD-related biomarkers via brain imaging devices is crucial for early diagnosis. In particular, "portable" brain imaging devices enable frequent diagnostic checks as a routine clinical tool, and therefore increase the possibility of early AD diagnosis. This study aimed to comprehensively investigate functional connectivity (FC) in the prefrontal cortex measured by a portable functional near-infrared spectroscopy (fNIRS) device during a working memory (WM) task known as the delayed matching to sample (DMTS) task. Differences in prefrontal FC between healthy control (HC) (n = 23) and CD groups (n = 23) were examined. Intra-group analysis (one-sample t-test) revealed significantly greater prefrontal FC, especially left- and inter-hemispheric FC, in the CD group than in the HC. These observations could be due to a compensatory mechanism of the prefrontal cortex caused by hippocampal degeneration. Inter-group analysis (unpaired two-sample t-test) revealed significant intergroup differences in left- and inter-hemispheric FC. These attributes may serve as a novel biomarker for early detection of MCI. In addition, our findings imply that portable fNIRS devices covering the prefrontal cortex may be useful for early diagnosis of MCI.

14.
J Cell Mol Med ; 24(1): 830-840, 2020 01.
Article in English | MEDLINE | ID: mdl-31692229

ABSTRACT

Pulmonary fibrosis (PF) is chronic and irreversible damage to the lung characterized by fibroblast activation and matrix deposition. Although recently approved novel anti-fibrotic agents can improve the lung function and survival of patients with PF, the overall outcomes remain poor. In this study, a novel imidazopurine compound, 3-(2-chloro-6-fluorobenzyl)-1,6,7-trimethyl-1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione (IM-1918), markedly inhibited transforming growth factor (TGF)-ß-stimulated reporter activity and reduced the expression of representative fibrotic markers, such as connective tissue growth factor, fibronectin, collagen and α-smooth muscle actin, on human lung fibroblasts. However, IM-1918 neither decreased Smad-2 and Smad-3 nor affected p38MAPK and JNK. Instead, IM-1918 reduced Akt and extracellular signal-regulated kinase 1/2 phosphorylation increased by TGF-ß. Additionally, IM-1918 inhibited the phosphorylation of fibroblast growth factor receptors 1 and 3. In a bleomycin-induced murine lung fibrosis model, IM-1918 profoundly reduced fibrotic areas and decreased collagen and α-smooth muscle actin accumulation. These results suggest that IM-1918 can be applied to treat lung fibrosis.


Subject(s)
Enzyme Inhibitors/pharmacology , Imidazoles/chemistry , Pulmonary Fibrosis/drug therapy , Receptor, Fibroblast Growth Factor, Type 1/antagonists & inhibitors , Receptor, Fibroblast Growth Factor, Type 3/antagonists & inhibitors , Transforming Growth Factor beta/metabolism , Animals , Antibiotics, Antineoplastic/toxicity , Bleomycin/toxicity , Fibronectins/genetics , Fibronectins/metabolism , Male , Mice , Mice, Inbred C57BL , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/pathology , Transforming Growth Factor beta/genetics
15.
Phys Rev Lett ; 123(21): 214301, 2019 Nov 22.
Article in English | MEDLINE | ID: mdl-31809129

ABSTRACT

We present a gradient-index crystal that offers extreme tunability in terms of manipulating the propagation of elastic waves. For small-amplitude excitations, we achieve control over wave transmission depth into the crystal. We numerically and experimentally demonstrate a boomeranglike motion of a wave packet injected into the crystal. For large-amplitude excitations on the same crystal, we invoke nonlinear effects. We numerically and experimentally demonstrate asymmetric wave transmission from two opposite ends of the crystal. Such tunable systems can thus inspire a novel class of designed materials to control linear and nonlinear elastic wave propagation in multiscales.

16.
Korean J Physiol Pharmacol ; 23(5): 367-379, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31496874

ABSTRACT

Although atopic dermatitis (AD) is known to be a representative skin disorder, it also affects the systemic immune response. In a recent study, myoblasts were shown to be involved in the immune regulation, but the roles of muscle cells in AD are poorly understood. We aimed to identify the relationship between mitochondria and atopy by genome-wide analysis of skeletal muscles in mice. We induced AD-like symptoms using house dust mite (HDM) extract in NC/Nga mice. The transcriptional profiles of the untreated group and HDM-induced AD-like group were analyzed and compared using microarray, differentially expressed gene and functional pathway analyses, and protein interaction network construction. Our microarray analysis demonstrated that immune response-, calcium handling-, and mitochondrial metabolism-related genes were differentially expressed. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology pathway analyses, immune response pathways involved in cytokine interaction, nuclear factor-kappa B, and T-cell receptor signaling, calcium handling pathways, and mitochondria metabolism pathways involved in the citrate cycle were significantly upregulated. In protein interaction network analysis, chemokine family-, muscle contraction process-, and immune response-related genes were identified as hub genes with many interactions. In addition, mitochondrial pathways involved in calcium signaling, cardiac muscle contraction, tricarboxylic acid cycle, oxidation-reduction process, and calcium-mediated signaling were significantly stimulated in KEGG and Gene Ontology analyses. Our results provide a comprehensive understanding of the genome-wide transcriptional changes of HDM-induced AD-like symptoms and the indicated genes that could be used as AD clinical biomarkers.

17.
Int J Mol Sci ; 20(19)2019 Sep 24.
Article in English | MEDLINE | ID: mdl-31554189

ABSTRACT

Class III receptor tyrosine kinase (RTK) inhibitors targeting mainly FLT3 or c-KIT have not been well studied in lung cancer. To identify a small molecule potentially targeting class III RTK, we synthesized novel small molecule compounds and identified 5-(4-bromophenyl)-N-(naphthalen-1-yl) oxazol-2-amine (AIU2001) as a novel class III RKT inhibitor. In an in vitro kinase profiling assay, AIU2001 inhibited the activities of FLT3, mutated FLT3, FLT4, and c-KIT of class III RTK, and the proliferation of NSCLC cells in vitro and in vivo. AIU2001 induced DNA damage, reactive oxygen species (ROS) generation, and cell cycle arrest in the G2/M phase. Furthermore, AIU2001 suppressed the DNA damage repair genes, resulting in the 'BRCAness'/'DNA-PKness' phenotype. The mRNA expression level of STAT5 was downregulated by AIU2001 treatment and knockdown of STAT5 inhibited the DNA repair genes. Our results show that compared to either drug alone, the combination of AIU2001 with a poly (ADP-ribose) polymerase (PARP) inhibitor olaparib or irradiation showed synergistic efficacy in H1299 and A549 cells. Hence, our findings demonstrate that AIU2001 is a candidate therapeutic agent for NSCLC and combination therapies with AIU2001 and a PARP inhibitor or radiotherapy may be used to increase the therapeutic efficacy of AIU2001 due to inhibition of DNA damage repair.


Subject(s)
Antineoplastic Agents/pharmacology , DNA Damage , DNA Repair/drug effects , Protein Kinase Inhibitors/pharmacology , Animals , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Synergism , Humans , Lung Neoplasms , Mice , Molecular Structure , Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Structure-Activity Relationship , Xenograft Model Antitumor Assays
18.
J Clin Med ; 8(2)2019 Feb 11.
Article in English | MEDLINE | ID: mdl-30754707

ABSTRACT

The authors identified that chemo-brain was induced after trastuzumab (TZB) therapy. In addition, atorvastatin (ATV) could rescue chemo-brain during trastuzumab (TZB) therapy. Enhanced therapeutic effect of TZB was confirmed after ATV therapy. We also investigated that there was no hair loss side effect due to ATV therapy. In an animal model, 150 µg TZB and five serial doses of 20 mg/kg ATV were administered. 18F-fluorodeoxyglucose Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) data were acquired. Statistical parametric mapping analysis and voxel-based morphometry analysis were performed to identify differences in glucose metabolism and gray matter concentration. The enhanced therapeutic efficacy of TZB after ATV treatment was assessed using a human epidermal growth factor receptor 2-positive gastric cancer model. We found a decrease in cerebral glucose metabolism and gray matter concentration in the frontal lobe following TZB therapy (p < 0.005). After subsequent ATV administration, glucose metabolism and regional gray matter concentration were rescued (p < 0.005). Cognitive impairment due to TZB and the rescue effect of ATV were confirmed using a passive avoidance test and quantitative real-time reverse transcription PCR. Furthermore, the penetration and accumulation of TZB in tumors increased by 100% after ATV co-administration, which resulted in an enhanced anti-cancer effect. Our study collectively demonstrates that ATV co-administration with TZB rescued the TZB-induced chemo-brain and enhances the therapeutic efficacy of TZB in tumors. We also showed that there was no hair loss during ATV therapy.

19.
Philos Trans A Math Phys Eng Sci ; 376(2127)2018 Aug 28.
Article in English | MEDLINE | ID: mdl-30037934

ABSTRACT

We propose a tunable cylinder-based granular system that is functionally graded in its stiffness distribution in space. With no initial compression given to the system, it supports highly nonlinear waves propagating under an impulse excitation. We investigate analytically, numerically and experimentally the ability to accelerate and decelerate the impulse wave without a significant scattering in the space domain. Moreover, the gradient in stiffness results in the scaling of contact forces along the chain. We envision that such tunable systems can be used for manipulating highly nonlinear impulse waves for novel sensing and impact mitigation purposes.This article is part of the theme issue 'Nonlinear energy transfer in dynamical and acoustical systems'.

20.
Nat Commun ; 9(1): 3018, 2018 07 27.
Article in English | MEDLINE | ID: mdl-30054484

ABSTRACT

The original version of this Article contained an error in second sentence of the Acknowledgements, which incorrectly read 'J.Y. and P.G.K. also acknowledge support from US-ARO (W911NF-15-1-0604) and US-AFOSR (FA9550-17-1-011), and P.G.K. also gratefully acknowledges support from the Stavros Niarchos Foundation via the Greek Diaspora Fellowship Program.' The correct version states 'US-AFOSR (FA9550-17-1-0114)' in place of 'US-AFOSR (FA9550-17-1-011)'. This has been corrected in both the PDF and HTML versions of the Article.

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