Publications by authors named "Hong Ji"

1,131 Publications

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DeepCUBIT: Predicting Lymphovascular Invasion or Pathological Lymph Node Involvement of Clinical T1 Stage Non-Small Cell Lung Cancer on Chest CT Scan Using Deep Cubical Nodule Transfer Learning Algorithm.

Front Oncol 2021 5;11:661244. Epub 2021 Jul 5.

Division of Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

The prediction of lymphovascular invasion (LVI) or pathological nodal involvement of tumor cells is critical for successful treatment in early stage non-small cell lung cancer (NSCLC). We developed and validated a Deep Cubical Nodule Transfer Learning Algorithm (DeepCUBIT) using transfer learning and 3D Convolutional Neural Network (CNN) to predict LVI or pathological nodal involvement on chest CT images. A total of 695 preoperative CT images of resected NSCLC with tumor size of less than or equal to 3 cm from 2008 to 2015 were used to train and validate the DeepCUBIT model using five-fold cross-validation method. We also used tumor size and consolidation to tumor ratio (C/T ratio) to build a support vector machine (SVM) classifier. Two-hundred and fifty-four out of 695 samples (36.5%) had LVI or nodal involvement. An integrated model (3D CNN + Tumor size + C/T ratio) showed sensitivity of 31.8%, specificity of 89.8%, accuracy of 76.4%, and AUC of 0.759 on external validation cohort. Three single SVM models, using 3D CNN (DeepCUBIT), tumor size or C/T ratio, showed AUCs of 0.717, 0.630 and 0.683, respectively on external validation cohort. DeepCUBIT showed the best single model compared to the models using only C/T ratio or tumor size. In addition, the DeepCUBIT model could significantly identify the prognosis of resected NSCLC patients even in stage I. DeepCUBIT using transfer learning and 3D CNN can accurately predict LVI or nodal involvement in cT1 size NSCLC on CT images. Thus, it can provide a more accurate selection of candidates who will benefit from limited surgery without increasing the risk of recurrence.
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http://dx.doi.org/10.3389/fonc.2021.661244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287408PMC
July 2021

N6-methyladenosine (m6A)-mediated up-regulation of long noncoding RNA LINC01320 promotes the proliferation, migration, and invasion of gastric cancer via miR495-5p/RAB19 axis.

Authors:
Naijun Hu Hong Ji

Bioengineered 2021 Dec;12(1):4081-4091

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.

Gastric cancer is one of the most common malignant tumors. Long non-coding RNAs play crucial roles in gastric cancer progression. This study investigated the effect of LINC01320 on malignant behaviors of gastric cancer cells and explored its possible molecular mechanism. LINC01320 expression in gastric cancer tissues and cell lines was measured by qRT-PCR. Cell proliferation, transwell, and cell cloning assays were used to detect the effect of LINC01320 on the proliferation, migration, and invasion abilities, respectively, of gastric cancer cells. Bioinformatics analysis was used to predict the binding of miR-495-5p with LINC01320 and RAB19. A luciferase reporter assay was performed to verify their interactions. Finally, the N-methyladenosine (m6A) modification of LINC01320 by METTL14 was identified through RIP experiments. LINC01320 was highly expressed in gastric cancer tissues and cells. LINC01320 overexpression promoted the proliferation, migration, and invasion of gastric cancer cells, while LINC01320 knockdown exerted the opposite effects. Moreover, miR-495-5p was predicted and demonstrated to target LINC01320 and RAB19. LINC01320 sponged miR-495-5p to regulate the expression of RAB19. Additionally, LINC01320-induced increases in cell viability, migration, and invasion of gastric cancer were alleviated by miR-495-5p and silenced RAB19. Furthermore, epigenetic studies showed that METTL14-mediated m6A modification led to LINC01320 up-regulation. METTL14 regulated the m6A modification of LINC01320. Overexpressed LINC01320 contributed to the aggressive phenotype of gastric cancer cells via regulating the miR-495-5p/RAB19 axis. This finding may provide new potential targets for treating gastric cancer.
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http://dx.doi.org/10.1080/21655979.2021.1953210DOI Listing
December 2021

DeepRePath: Identifying the Prognostic Features of Early-Stage Lung Adenocarcinoma Using Multi-Scale Pathology Images and Deep Convolutional Neural Networks.

Cancers (Basel) 2021 Jul 1;13(13). Epub 2021 Jul 1.

Division of Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.

The prognosis of patients with lung adenocarcinoma (LUAD), especially early-stage LUAD, is dependent on clinicopathological features. However, its predictive utility is limited. In this study, we developed and trained a DeepRePath model based on a deep convolutional neural network (CNN) using multi-scale pathology images to predict the prognosis of patients with early-stage LUAD. DeepRePath was pre-trained with 1067 hematoxylin and eosin-stained whole-slide images of LUAD from the Cancer Genome Atlas. DeepRePath was further trained and validated using two separate CNNs and multi-scale pathology images of 393 resected lung cancer specimens from patients with stage I and II LUAD. Of the 393 patients, 95 patients developed recurrence after surgical resection. The DeepRePath model showed average area under the curve (AUC) scores of 0.77 and 0.76 in cohort I and cohort II (external validation set), respectively. Owing to low performance, DeepRePath cannot be used as an automated tool in a clinical setting. When gradient-weighted class activation mapping was used, DeepRePath indicated the association between atypical nuclei, discohesive tumor cells, and tumor necrosis in pathology images showing recurrence. Despite the limitations associated with a relatively small number of patients, the DeepRePath model based on CNNs with transfer learning could predict recurrence after the curative resection of early-stage LUAD using multi-scale pathology images.
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http://dx.doi.org/10.3390/cancers13133308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268823PMC
July 2021

Effect of Human or Mouse IL-7 on the Homeostasis of Porcine T Lymphocytes.

Immune Netw 2021 Jun 25;21(3):e24. Epub 2021 Jun 25.

Department of Pharmacy, Korea University, Sejong 30019, Korea.

Due to the inconsistent fluctuation of blood supply for transfusion, much attention has been paid to the development of artificial blood using other animals. Although mini-pigs are candidate animals, contamination of mini-pig T cells in artificial blood may cause a major safety concern. Therefore, it is important to analyze the cross-reactivity of IL-7, the major survival factor for T lymphocytes, between human, mouse, and mini-pig. Thus, we compared the protein sequences of IL-7 and found that porcine IL-7 was evolutionarily different from human IL-7. We also observed that when porcine T cells were cultured with either human or mouse IL-7, these cells did not increase the survival or proliferation compared to negative controls. These results suggest that porcine T cells do not recognize human or mouse IL-7 as their survival factor.
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http://dx.doi.org/10.4110/in.2021.21.e24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263216PMC
June 2021

Programmable Dynamics of Exchange-Biased Domain Wall via Spin-Current-Induced Antiferromagnet Switching.

Adv Sci (Weinh) 2021 Jul 15:e2100908. Epub 2021 Jul 15.

Department of Emerging Materials Science, Daegu Gyeongbuk Institute of Science and Technology (DGIST), 333 Techno jungang-daero, Daegu, 42988, Republic of Korea.

Magnetic domain wall (DW) motion in perpendicularly magnetized materials is drawing increased attention due to the prospect of new type of information storage devices, such as racetrack memory. To augment the functionalities of DW motion-based devices, it is essential to improve controllability over the DW motion. Other than electric current, which is known to induce unidirectional shifting of a train of DWs, an application of in-plane magnetic field also enables the control of DW dynamics by rotating the DW magnetization and consequently modulating the inherited chiral DW structure. Applying an external bias field, however, is not a viable approach for the miniaturization of the devices as the external field acts globally. Here, the programmable exchange-coupled DW motion in the antiferromagnet (AFM)/ferromagnet (FM) system is demonstrated, where the role of an external in-plane field is replaced by the exchange bias field from AFM layer, enabling the external field-free modulations of DW motions. Interestingly, the direction of the exchange bias field can also be reconfigured by simply injecting spin currents through the device, enabling electrical and programmable operations of the device. Furthermore, the result inspires a prototype DW motion-based device based on the AFM/FM heterostructure, that could be easily integrated in logic devices.
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http://dx.doi.org/10.1002/advs.202100908DOI Listing
July 2021

Comparison of the effects of normal and low blood pressure regulation on the optic nerve sheath diameter in robot assisted laparoscopic radical prostatectomy.

Anesth Pain Med (Seoul) 2021 Apr 23. Epub 2021 Apr 23.

Department of Anesthesiology and Pain Medicine, Keimyung University Dongsan Hospital, Daegu, Korea.

Background: Robot-assisted laparoscopic radical prostatectomy is an advanced and popular surgical technique. However, increased intracranial pressure which is caused by CO2 pneumoperitoneum and Trendelenburg position is the main cerebrovascular effect. Measurement of optic nerve sheath diameter using ocular ultrasound is a noninvasive and reliable method for the assessment of intracranial pressure. The primary endpoint of this study was to identify whether low blood pressure regulation has any benefit in attenuating an increase of optic nerve sheath diameter during robot-assisted laparoscopic radical prostatectomy.

Methods: Optic nerve sheath diameter and cerebral oxygen saturation were measured at baseline (supine position), one and two hours after pneumoperitoneum and Trendelenburg position respectively, and after return to supine position in normal (n = 27) and low blood pressure groups (n = 24).

Results: Mean optic nerve sheath diameter values measured at one and two hours after pneumoperitoneum and Trendelenburg position were significantly increased compared to the baseline value (P < 0.001 in normal blood pressure group; P = 0.003 in low blood pressure group). However, the mean optic nerve sheath diameter and cerebral oxygen saturation measured at any of the time points as well as degrees of change between the two groups did not show any significant changes. The peak values of optic nerve sheath diameter in normal and low blood pressure groups demonstrated 14.9% and 9.2% increases, respectively.

Conclusions: Low blood pressure group demonstrated an effect in maintaining an increase of optic nerve sheath diameter less than 10% during CO2 pneumoperitoneum and Trendelenburg position.
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http://dx.doi.org/10.17085/apm.20097DOI Listing
April 2021

ATF6-DGAT pathway is involved in TLR7-induced innate immune response in Ctenopharyngodon idellus kidney cells.

Dev Comp Immunol 2021 Jul 3;124:104197. Epub 2021 Jul 3.

College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China. Electronic address:

DGAT1 and DGAT2 are two acyl-CoA:diacylglycerol O-acyltransferase (DGAT) enzymes that catalyze the final step in triglyceride (TG) synthesis. TGs are the primary constituents of lipid droplets (LDs). Although it has been demonstrated that LDs modulate immune and inflammatory responses in CIK cells, little is known about whether DGAT1 and DGAT2 involve in this process. Firstly, grass carp DGAT2 was isolated and characterized, encoding 361 amino acids, and all DGAT2 proteins in genomic structures are conserved in vertebrates. Then, using TLR7 agonist, we induced LDs accumulation in CIK cells. Only DGAT1b and DGAT2 were upregulated in forming TLR7 agonist induced-LDs. Next, we utilized small-molecule inhibitors of DGAT1 and DGAT2. The results indicated that DGAT1 inactivation attenuated TG content and the relative expressions of IFNα3, NF-κB, IL-1β, and TNFα genes, whereas DGAT2 inhibition decreased TG content and the relative expressions of MyD88, IRF7, IFNα3, NF-κB, IL-1β, and TNFα genes, implying that DGAT1-generated LDs and DGAT2-generated LDs contribute to TLR7-induced immune response via different signaling pathways. Finally, inhibiting ATF6 effectively decreased DGAT-generated LDs accumulation and the expression of TLR7 signaling-related genes induced by TLR7 agonist, implying that ATF6 UPR pathway may mediate the role of DGAT-generated LDs in TLR7 signaling. Overall, we demonstrate that DGAT1 and DGAT2-catalyzed TAG synthesis may generate different LDs to provide distinct signaling platforms for innate TLR7 signaling.
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http://dx.doi.org/10.1016/j.dci.2021.104197DOI Listing
July 2021

Clinical outcomes in patients with lung cancer admitted to intensive care units.

Ann Transl Med 2021 May;9(10):836

Department of Internal Medicine, School of Medicine, Kangwon National University, Kangwon National University Hospital, Chuncheon, Republic of Korea.

Background: Recent advances in critical care and infection control have led to improved intensive care unit (ICU) survival rates. However, controversy exists regarding the benefits of ICU treatment for patients with lung cancer. In this study, we evaluated the clinical outcomes of patients from the Korean national database, who had been diagnosed with lung cancer and had received ICU treatment.

Methods: We investigated patients in Korea who had been newly diagnosed with lung cancer between January 1, 2008 and December 31, 2010. We classified these critically ill patients with lung cancer according to their lung cancer treatment pathways, with a specific focus on those who had undergone ICU treatment.

Results: We found that 31.3% of patients newly diagnosed with lung cancer had been admitted to the ICU for any reason, and 18.5% of patients with lung cancer were admitted to the ICU for reasons other than postoperative surgical lung cancer resection. The ICU mortality rate was 2.9% in patients admitted to the ICU for postoperative care and 47.5% in patients admitted for other reasons. Clinical cancer staging (HR, 7.02; 95% CI, 5.82-8.48; P<0.01) and the need for mechanical ventilator (HR, 1.34; 95% CI, 1.27-1.41; P<0.01) were independently associated with ICU mortality. The importance of mechanical ventilator intervention as a predictor for survival was significantly greater in the earlier stages of lung cancer (HR, 1.97; 95% CI, 1.15-3.38; P<0.01).

Conclusions: This study suggests that goals and treatment plans for critically ill patients with lung cancer should be determined by the individual patient's clinical cancer stage, regardless of the reason for admission to the ICU.
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http://dx.doi.org/10.21037/atm-21-298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184420PMC
May 2021

Exploring the evidence for epigenetic regulation of environmental influences on child health across generations.

Commun Biol 2021 Jun 22;4(1):769. Epub 2021 Jun 22.

Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, UNC Chapel Hill, Chapel Hill, NC, USA.

Environmental exposures, psychosocial stressors and nutrition are all potentially important influences that may impact health outcomes directly or via interactions with the genome or epigenome over generations. While there have been clear successes in large-scale human genetic studies in recent decades, there is still a substantial amount of missing heritability to be elucidated for complex childhood disorders. Mounting evidence, primarily in animals, suggests environmental exposures may generate or perpetuate altered health outcomes across one or more generations. One putative mechanism for these environmental health effects is via altered epigenetic regulation. This review highlights the current epidemiologic literature and supporting animal studies that describe intergenerational and transgenerational health effects of environmental exposures. Both maternal and paternal exposures and transmission patterns are considered, with attention paid to the attendant ethical, legal and social implications.
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http://dx.doi.org/10.1038/s42003-021-02316-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219763PMC
June 2021

Procyanidin B2 alleviates liver injury caused by cold stimulation through Sonic hedgehog signalling and autophagy.

J Cell Mol Med 2021 Jun 21. Epub 2021 Jun 21.

College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China.

Procyanidin B2 (PB2), a naturally occurring flavonoid abundant in a wide range of fruits, has been shown to exert antioxidant, anti-inflammatory and anticancer properties. However, the role of PB2 in the prevention of cold stimulation (CS)-induced liver injury. The present study was undertaken to determine the effects of PB2 on liver injury induced by cold stimulation and its potential molecular mechanisms. The present study results showed that treatment with PB2 significantly reduced CS-induced liver injury by alleviating histopathological changes and serum levels of alanine transaminase and aspartate transaminase. Moreover, treatment with PB2 inhibited secretion of inflammatory cytokines and oxidative stress in cold-stimulated mice. PB2 reduced cold stimulation-induced inflammation by inhibiting TLR4/NF-κB and Txnip/NLRP3 signalling. Treatment with PB2 reduced oxidative stress by activating Nrf-2/Keap1, AMPK/GSK3β signalling pathways and autophagy. Furthermore, simultaneous application of Shh pathway inhibitor cyclopamine proved that PB2 targets the Hh pathway. More importantly, co-treatment with PB2 and cyclopamine showed better efficacy than monotherapy. In conclusion, our findings provide new evidence that PB2 has protective potential against CS-induced liver injury, which might be closely linked to the inhibition of Shh signalling pathway.
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http://dx.doi.org/10.1111/jcmm.16733DOI Listing
June 2021

Current Opinion on Prucalopride in Gastroparesis and Chronic Constipation Treatment: A Focus on Patient Selection and Safety.

Authors:
Ji Taek Hong

Ther Clin Risk Manag 2021 8;17:601-615. Epub 2021 Jun 8.

Division of Gastroenterology, Department of Medicine, Ewha Womans University College of Medicine, Seoul, Korea.

Prucalopride is a third-generation, highly selective 5-hydroxytryptamine 4 (5-HT4) receptor agonist. Many recent studies indicate prucalopride may play an important role in various motility disorders. The aim of this study was to investigate safety and patient selection considerations when using prucalopride as gastroparesis and chronic constipation treatment. We systematically searched PubMed, Embase, the Cochrane Central Register and ClinicalTrials.gov, and we reviewed all studies that evaluated prucalopride for the treatment of gastroparesis and chronic idiopathic constipation in adults. Prucalopride is an effective and safe option based on all the studies currently conducted. Thus, it may be the first-line treatment in the future. Prucalopride has the potential to be useful in the treatment of functional constipation and other forms of gastrointestinal diseases (eg, gastroparesis). Through the research on this potential, prucalopride is expected to be a useful and versatile option for treating gastrointestinal diseases in the future.
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http://dx.doi.org/10.2147/TCRM.S269330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197617PMC
June 2021

Oxygen-generating glycol chitosan-manganese dioxide nanoparticles enhance the photodynamic effects of chlorin e6 on activated macrophages in hypoxic conditions.

Int J Biol Macromol 2021 Aug 10;184:20-28. Epub 2021 Jun 10.

Department of Systems Biotechnology, Chung-Ang University, Anseong-si, Gyeonggi-do 17546, Republic of Korea. Electronic address:

This study aimed to investigate the use of glycol chitosan (GC) for the synthesis of MnO nanoparticles (NPs) and to evaluate whether the prepared GC-MnO NPs enhance the light-triggered photodynamic effects of chlorin e6 (Ce6) via the generation of oxygen and alleviation of hypoxia in lipopolysaccharide (LPS)-activated macrophages (RAW 264.7), which produce excessive amounts of reactive oxygen species (ROS). GC-MnO NPs were synthesized by a simple reaction between GC and KMnO in water. The prepared GC-MnO NPs were spherical in shape, with a mean diameter of approximately 60 nm. The particles effectively generated oxygen via HO-induced degradation under hypoxic conditions, which led to an increase in the singlet oxygen levels upon laser irradiation. Furthermore, GC-MnO NPs significantly enhanced the light-triggered photodynamic effects of Ce6 on activated macrophages under hypoxic conditions, as shown by the increased levels of cell death and cell membrane damage in activated macrophages. Therefore, these results suggest that GC can be used as an alternative natural polymer for the synthesis of MnO NPs and that oxygen-generating GC-MnO NPs enhance the light-triggered photodynamic effects of Ce6 on activated macrophages by alleviating hypoxia.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.036DOI Listing
August 2021

Targeted mutagenesis in mouse cells and embryos using an enhanced prime editor.

Genome Biol 2021 Jun 3;22(1):170. Epub 2021 Jun 3.

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

Prime editors, novel genome-editing tools consisting of a CRISPR-Cas9 nickase and an engineered reverse transcriptase, can induce targeted mutagenesis. Nevertheless, much effort is required to optimize and improve the efficiency of prime-editing. Herein, we introduce two strategies to improve the editing efficiency using proximal dead sgRNA and chromatin-modulating peptides. We used enhanced prime-editing to generate Igf2 mutant mice with editing frequencies of up to 47% and observed germline transmission, no off-target effects, and a dwarf phenotype. This improved prime-editing method can be efficiently applied to cell research and to generate mouse models.
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http://dx.doi.org/10.1186/s13059-021-02389-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173820PMC
June 2021

Early Differentiation of Stress Cardiomyopathy from Acute Anterior Wall Myocardial Using Changing Cardiac Enzyme Patterns.

J Cardiovasc Imaging 2021 Jul 23;29(3):228-233. Epub 2021 Feb 23.

Division of Cardiology, Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University, Seoul, Korea.

Background: Most patients with acute anterior wall ST elevation myocardial infarction (STEMI) or stress cardiomyopathy (SCMP) show elevations in cardiac enzymes that peak within 24 hours. The changing pattern of cardiac enzymes can be an early clue to the differentiation of anterior STEMI and SCMP.

Methods: This study was a retrospective analysis (matching cases and respective control subjects) performed at a single center. We compared 27 patients with SCMP and 30 patients with anterior STEMI. We used laboratory data included cardiac marker, such as the initial creatine kinase MB (CK-MB) fraction and troponin T (Tn-T), at admission and peak CK-MB and Tn-T at follow up.

Results: The mean age was 69.3 ± 14.1 years, and 38.6% of patients were female. The SCMP patients were older, more often female, and had lower left ventricular ejection fractions than the anterior STEMI patients. The initial CK-MB was higher in the anterior STEMI group than in the SCMP group. In contrast, the initial Tn-T level was not significantly different between the 2 groups. Peak CK-MB and Tn-T levels and change from initial levels were significantly greater in the anterior STEMI group than they were in the SCMP group. SCMP could be differentiated from anterior STEMI based on peak CK-MB > 46.65 ng/mL or Tn-T > 1.56 ng/mL.

Conclusions: Follow-up changes in cardiac enzymes can be an effective early tool for differentiating SCMP from anterior STEMI.
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http://dx.doi.org/10.4250/jcvi.2020.0167DOI Listing
July 2021

A catenin of the plakophilin-subfamily, Pkp3, responds to canonical-Wnt pathway components and signals.

Biochem Biophys Res Commun 2021 Jul 28;563:31-39. Epub 2021 May 28.

Department of Genetics, University of Texas MD Anderson Cancer Center, Houston TX, 77030, USA; University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston TX, 77030, USA. Electronic address:

Vertebrate beta-catenin plays a key role as a transducer of canonical-Wnt signals. We earlier reported that, similar to beta-catenin, the cytoplasmic signaling pool of p120-catenin-isoform1 is stabilized in response to canonical-Wnt signals. To obtain a yet broader view of the Wnt-pathway's impact upon catenin proteins, we focused upon plakophilin3 (plakophilin-3; Pkp3) as a representative of the plakophilin-catenin subfamily. Promoting tissue integrity, the plakophilins assist in linking desmosomal cadherins to intermediate filaments at desmosome junctions, and in common with other catenins they perform additional functions including in the nucleus. In this report, we test whether canonical-Wnt pathway components modulate Pkp3 protein levels. We find that in common with beta-catenin and p120-catenin-isoform1, Pkp3 is stabilized in the presence of a Wnt-ligand or a dominant-active form of the LRP6 receptor. Pkp3's levels are conversely lowered upon expressing destruction-complex components such as GSK3β and Axin, and in further likeness to beta-catenin and p120-isoform1, Pkp3 associates with GSK3beta and Axin. Finally, we note that Pkp3-catenin trans-localizes into the nucleus in response to Wnt-ligand and its exogenous expression stimulates an accepted Wnt reporter. These findings fit an expanded model where context-dependent Wnt-signals or pathway components modulate Pkp3-catenin levels. Future studies will be needed to assess potential gene regulatory, cell adhesive, or cytoskeletal effects.
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http://dx.doi.org/10.1016/j.bbrc.2021.05.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252864PMC
July 2021

Informant (Dis)Agreement on Ratings of Challenging Behaviors and Social Communication in Preschool Children With Autism Spectrum Disorder.

J Speech Lang Hear Res 2021 Jul 28;64(7):2766-2775. Epub 2021 May 28.

Center for Autism and Related Disorders, Kennedy Krieger Institute, Baltimore, MD.

Purpose Cross-informant ratings are considered best practice for assessing children with autism spectrum disorder (ASD). However, informant disagreement often occurs, which can pose significant challenges to various aspects of clinical services. This study explored the degree of parent and speech-language pathologist (SLP) agreement on ratings of challenging behaviors and social communication skills in preschool children with ASD. Method Fifty-eight informant ratings of challenging behaviors and social communication skills were collected from parents and SLPs on the same 29 preschool children with ASD ( = 49.93 months, = 11.67 months) using the Pervasive Developmental Disorder Behavior Inventory. Parent versus SLP group rating comparisons were assessed with paired tests and Cohen's effect sizes. Intraclass correlation coefficients were calculated to examine interrater reliability between individual parent and SLP ratings. Bland-Altman plots were generated to evaluate informant agreement across the entire range of Pervasive Developmental Disorder Behavior Inventory composite scores. Results Group comparisons indicated that parents rated arousal regulation problems as more severe than SLPs, with no other group differences observed. Parents and SLPs exhibited poor agreement on ratings of challenging behaviors; however, moderate to good agreement was observed for social communication ratings. Conclusions These results highlight the importance of including parents in the assessment and treatment planning process for preschool children with ASD, as parents may report key behavioral concerns that clinicians may not otherwise observe. Understanding behaviors that may be more prone to informant disagreement has implications for promoting a shared understanding of behavioral concerns and treatment targets between parents and clinicians.
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http://dx.doi.org/10.1044/2021_JSLHR-20-00707DOI Listing
July 2021

Dysregulation in Children and Adolescents Presenting to a Multidisciplinary Autism Clinic.

J Autism Dev Disord 2021 May 19. Epub 2021 May 19.

Center for Autism and Related Disorders, Kennedy Krieger Institute, 3901 Greenspring Ave, Baltimore, MD, 21211, USA.

Research indicates that children with autism spectrum disorder (ASD) frequently exhibit dysregulation, which refers to poorly coordinated affective, behavioral, and cognitive responses to a given situation. We examined the characteristics of dysregulation in children presenting to a multidisciplinary ASD clinic for an ASD diagnostic evaluation. Sixty percent of children presenting for an ASD evaluation exhibited dysregulation. Dysregulation prevalence was higher in children without ASD versus with ASD (69% versus 56%). Severe dysregulation was higher in children without ASD (29% versus 16%). Both groups with severe dysregulation were equally likely to be taking psychiatric medications, however, children with ASD were less likely to be receiving therapy. These findings highlight the importance of implementing dysregulation screening and treatment protocols in ASD centers.
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http://dx.doi.org/10.1007/s10803-021-05056-yDOI Listing
May 2021

Correlations Between Cognitive Functions and Clinical Symptoms in Adolescents With Complex Post-traumatic Stress Disorder.

Front Public Health 2021 28;9:586389. Epub 2021 Apr 28.

Department of Psychiatry, Chung-Ang University Hospital, Seoul, South Korea.

Complex post-traumatic stress disorder (C-PTSD) is characterized by the typical symptoms of PTSD, in addition to affective dysregulation, negative self-concept, and disturbances in interpersonal relationships. Children and adolescents with C-PTSD have been reported to have deficits in emotional and cognitive functions. We hypothesized that the following are associated with the severity of C-PTSD symptoms: (1) adolescents with C-PTSD who show deficits in emotional perception and cognitive functions, including executive function and attention; and (2) deficits in neurocognitive functions. Information on 69 adolescents with PTSD, aged 10-19 years, was gathered from seven shelters. All participants were assessed using complete clinical scales, including the C-PTSD Interview and Depression, Anxiety, and Stress Scales, and neurocognitive function tests, including the emotional perception, mental rotation, and modified Tower of London tests. Adolescents with C-PTSD were more likely to have a history of sexual assault, dissociation, and self-harm than those with PTSD. The total and subscale scores of the C-PTSD Interview Scale in adolescents with C-PTSD were higher than that in adolescents with PTSD. In addition, neurocognitive functions, including emotional perception, attention, and working memory, were correlated with the severity of C-PTSD symptoms. Adolescents with C-PTSD experienced more serious clinical symptoms and showed more deficits in neurocognitive functions than adolescents with PTSD. Clinicians should pay careful attention toward the emotional and neurocognitive functions when assessing and treating patients with C-PTSD.
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http://dx.doi.org/10.3389/fpubh.2021.586389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113386PMC
May 2021

Preliminary study of ovariectomy and chronic losartan-induced alterations in brain AT receptors.

Brain Res 2021 Sep 13;1766:147520. Epub 2021 May 13.

College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, United States; Department of Pharmacology and Physiology, School of Medicine, Georgetown University, Washington, DC, United States. Electronic address:

Women who undergo oophorectomy prior to the age of natural menopause have a higher risk of neurological and psychological impairment. Treatment with the angiotensin receptor blocker (ARB) losartan for 10 weeks following ovariectomy of Long-Evans rats at 3 months of age reduced the ovariectomy-induced cognitive decrements. Following completion of the behavioral experiments, (Campos et al., 2019), the brains were harvested for preliminary receptor autoradiographic studies of AT receptor (ATR) binding in selected brain regions using quantitative densitometric analysis of autoradiograms of I-sarcosine, isoleucine angiotensin II binding. Four of the brain regions (amygdala, ventral subiculum, piriform cortex, and cingulate cortex) are associated with cognitive and emotional behavior while one (lateral hypothalamus) is associated with homeostasis. The density of ATR varied by region: ventral subiculum > amygdala and cingulate cortex, and piriform cortex > cingulate cortex. Losartan treatment decreased ATR binding in the ventral subiculum of sham and ovariectomized rats by 41.6%, and 46% in the piriform cortex of the sham rats, but tended to increase ATR binding in the piriform cortex and cingulate cortex 77% and 107%, respectively, in the ovariectomized rats. ATR binding did not differ significantly between intact male and sham-vehicle female rats among surveyed brain regions. These results suggest that losartan-induced changes in brain ATR expression may contribute to the reduced anxiety-like behavior and memory impairments seen in ovariectomized rats, but replication of these observations will be needed to determine the extent to which brain ATR changes mediate the adverse behavioral effects of ovariectomy.
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http://dx.doi.org/10.1016/j.brainres.2021.147520DOI Listing
September 2021

Digital PCR Detection of mtDNA/gDNA Ratio in Embryo Culture Medium for Prediction of Embryo Development Potential.

Pharmgenomics Pers Med 2021 30;14:521-531. Epub 2021 Apr 30.

Department of Reproductive Medicine, Women and Children's Hospital Affiliated to Xiamen University, Xiamen, Fujian, People's Republic of China.

Purpose: The ratio of mitochondrial DNA to genomic DNA (mtDNA/gDNA) in embryo culture medium as a predictor of embryonic development is a new method of noninvasive embryo screening. However, current tests based on this concept have proven inconsistent. The aim of this study was to define the predictive value of the ratio of mtDNA/gDNA for embryonic developmental potential.

Materials And Methods: We used digital PCR to measure mtDNA/gDNA ratios in day 3 culture media of 223 embryos from 56 patients. We compared the relationship between the predictive value of mtDNA/gDNA ratio and each of embryo fragmentation, embryo morphological grade, and blastocyst formation.

Results: mtDNA/gDNA ratio decreased significantly with a decrease in embryo rating: 22.54 (44.66); 31.25 (36.97) and 46.33 (57.11); Grades A vs C, = 0.006; B vs C, = 0.015. mtDNA/gDNA ratio increased overall with an increase in embryo fragment content but did not differ significantly between high-, -medium, and poor-quality embryos. Interestingly, this trend differed from that of the unformed blastocysts. mtDNA/gDNA ratio of cleavage stage embryos forming blastocysts was lower (=0.005). Trends of mtDNA/gDNA ratio differed according to inner cell mass (ICM) and trophectoderm (TE) levels, but not significantly. mtDNA/gDNA ratio in day 3 culture medium was not significantly improved over morphological scores.

Conclusion: We hereby show the correlation of mtDNA/gDNA ratio in the culture medium of developing embryos. The correlation between the mtDNA/gDNA ratio and early embryonic development was controversial. Furthermore, an increase in mtDNA/gDNA ratio might indicate reduced development potential, but the difference remains insufficient for application as a clinical predictor.
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http://dx.doi.org/10.2147/PGPM.S304747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096441PMC
April 2021

Negative Air Ions Alleviate Particulate Matter-Induced Inflammation and Oxidative Stress in the Human Keratinocyte Cell Line HaCaT.

Ann Dermatol 2021 Apr 8;33(2):116-121. Epub 2021 Mar 8.

Department of Dermatology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.

Background: Recent studies have revealed that particulate matter induces inflammation, oxidative stress, and several skin diseases. Experimental results have also shown that negative air ions are highly effective in removing particulate matter-induced inflammation.

Objective: The present study aimed to investigate whether negative air ions can inhibit inflammatory responses and reduce oxidative stress in HaCaT cells exposed to particulate matters.

Methods: HaCaT cells were treated with particulate matter in the presence or absence of negative air ions and the viability was evaluated by the MTT assay. Reactive oxygen species (ROS) generation was quantified by the dichlorodihydrofluorescein diacetate assay. The expression of genes and proteins was analyzed by real-time polymerase chain reaction and Western blot. Levels of inflammatory cytokines were quantified by enzyme-linked immunosorbent assay.

Results: Negative air ions were observed to downregulate the mRNA and protein levels of particulate matter-induced pro-inflammatory cytokines in HaCaT cells. In addition, negative air ion treatment suppressed particulate matter-induced intracellular ROS generation, p38 mitogen-activated protein kinase activation, and activator protein 1 (c-Fos and c-Jun) activation.

Conclusion: Our findings indicate that negative air ions exert anti-inflammatory and antioxidant effects in HaCaT cells exposed to particulate matter. Therefore, negative air ions can be used for the prevention and treatment of particulate matter-related inflammatory skin diseases.
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http://dx.doi.org/10.5021/ad.2021.33.2.116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082002PMC
April 2021

Effects of Particulate Matter in a Mouse Model of Oxazolone-Induced Atopic Dermatitis.

Ann Dermatol 2020 Dec 11;32(6):496-507. Epub 2020 Nov 11.

Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Korea.

Background: Recent epidemiological studies have demonstrated that air pollution is associated with the inflammatory response and may aggravate inflammatory skin diseases such as atopic dermatitis (AD). However, it is unclear whether particulate matter (PM) aggravates AD symptoms.

Objective: The aim of this study was to investigate whether PM exposure affects the skin barrier dysfunction and aggravates AD symptoms using human keratinocytes (HaCaT) cells and a mouse model of oxazolone-induced AD-like skin.

Methods: Standard reference material (SRM) 1649b, which mainly comprises polycyclic aromatic hydrocarbons, was used as the reference PM. HaCaT cells and mouse model of oxazolone-induced AD-like skin were treated with PM. The mRNA or protein expression levels of stratum corneum (SC) and tight junction (TJ) proteins, inflammatory cytokines, as well as clinical and histological changes of the AD-like skin of mouse model were evaluated. The expression of genes and proteins was analyzed by real-time polymerase chain reaction and Western blotting. Levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay.

Results: The results revealed that PM downregulates the expression levels of several SC and TJ-related proteins in the mouse model with AD-like skin. Clinically, epidermal and dermal thickness was significantly increased and dermal inflammation was prominent in PM treated AD-like skin.

Conclusion: In conclusion, we found that PM aggravates skin barrier dysfunction, clinically augmenting epidermal and dermal thickening with dermal inflammation in AD-like skin. These results suggest that PM may trigger the exacerbation of AD symptoms via skin barrier dysfunction-related mechanisms.
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http://dx.doi.org/10.5021/ad.2020.32.6.496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875236PMC
December 2020

Mini-invasive treatment with arthroscopic shaver for chronic non-infective prepatellar bursitis.

Asian J Surg 2021 Jun 20;44(6):928-929. Epub 2021 Apr 20.

Xing'an League People's Hospital, 66 Hanshan West Street, Ulanhot, Inner Mongolia, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2021.04.001DOI Listing
June 2021

The potential impact of systemic anti-inflammatory therapies in psoriasis on major adverse cardiovascular events: a Korean nationwide cohort study.

Sci Rep 2021 Apr 21;11(1):8588. Epub 2021 Apr 21.

Department of Dermatology, Konkuk University School of Medicine, 120-1 Neungdong-ro, Gwangjin-gu, Seoul, 143-729, Republic of Korea.

This nationwide population-based cohort study aimed to investigate the impact of systemic anti-inflammatory treatment on the major adverse cardiovascular events (MACE) risk in patients with psoriasis from January 2006 to December 2018, using a database provided by the Korean National Health Insurance Service. Patients were grouped based on the following treatment modalities: biologics, phototherapy, methotrexate, cyclosporine, and mixed conventional systemic agents. Patients who had not received any systemic treatment were assigned to the control cohort. The incidence of MACE per 1000 person-year was 3.5, 9.3, 12.1, 28.4, 39.5, and 14.5 in the biologic, phototherapy, methotrexate, cyclosporine, mixed conventional systemic agents, and control cohorts, respectively. During the 36-month follow-up, the cumulative incidence of MACE in the phototherapy and biologic cohorts remained lower than that of other treatment modalities. Cyclosporine (hazard ratio (HR) = 2.11, 95% confidence interval (CI) = 1.64-2.71) and mixed conventional systemic agents (HR = 2.57, 95% CI = 2.05-3.22) treatments were associated with increased MACE risk. Methotrexate treatment was not associated with MACE. Our finding demonstrates that treatment modalities may affect cardiovascular comorbidities in patients with psoriasis. Thus, an appropriate combination of anti-psoriatic therapies should be considered to manage patients with high cardiovascular risk.IRB approval status: Waiver decision was obtained by the institutional review board, Konkuk University Hospital, Seoul, Republic of Korea (KUH1120107).
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http://dx.doi.org/10.1038/s41598-021-87766-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060423PMC
April 2021

Thoracoscopic anterior mediastinal mass removal using an articulating laparoscopic instrument.

Interact Cardiovasc Thorac Surg 2021 Apr 21. Epub 2021 Apr 21.

Department of Thoracic and Cardiovascular Surgery, Korea University Guro Hospital, College of Medicine, Korea University, Seoul, Republic of Korea.

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http://dx.doi.org/10.1093/icvts/ivab110DOI Listing
April 2021

Screening for Infection Using Beijing/K Strain-Specific Peptides in a School Outbreak Cohort.

Front Cell Infect Microbiol 2021 18;11:599386. Epub 2021 Mar 18.

Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.

Background: The Beijing strain of () has been most frequently isolated from TB patients in South Korea, and the hyper-virulent Beijing/K genotype is associated with TB outbreaks. To examine the diagnostic potential of Beijing/K-specific peptides, we performed IFN-γ release assays (IGRA) using a MTBK antigen tube containing Beijing/K MTBK_24800, ESAT-6, and CFP-10 peptides in a cohort studied during a school TB outbreak.

Methods: A total of 758 contacts were investigated for infection, and 43 contacts with latent TB infection (LTBI) and 25 active TB patients were enrolled based on serial screening with QuantiFERON-TB Gold In-Tube tests followed by clinical examinations. Blood collected in MTBK antigen tubes was utilized for IGRA and multiplex cytokine bead arrays. Immune responses were retested in 24 patients after TB treatment, and disease progression was investigated in subjects with LTBI.

Results: Total proportions of active disease and LTBI during the outbreak were 3.7% (28/758) and 9.2% (70/758), respectively. All clinical isolates had a Beijing/K genotype. IFN-γ responses to the MTBK antigen identified infection and distinguished between active disease and LTBI. After anti-TB treatment, IFN-γ responses to the MTBK antigen were significantly reduced, and strong TNF-α responses at diagnosis were dramatically decreased.

Conclusions: MTBK antigen-specific IFN-γ has diagnostic potential for differentiating infection from healthy controls, and between active TB and LTBI as well. In addition, TNF-α is a promising marker for monitoring therapeutic responses. These data provide informative readouts for TB diagnostics and vaccine studies in regions where the Beijing/K strain is endemic.
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http://dx.doi.org/10.3389/fcimb.2021.599386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044942PMC
June 2021

Epidemiology of 631 Cases of COVID-19 Identified in Jiangsu Province Between January 1st and March 20th 2020: Factors Associated with Disease Severity and Analysis of Zero Mortality.

Med Sci Monit 2021 Apr 17;27:e929986. Epub 2021 Apr 17.

Department of Acute Infectious Disease Control and Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China (mainland).

BACKGROUND This retrospective study aimed to investigate the factors associated with disease severity and patient outcomes in 631 patients with COVID-19 who were reported to the Jiangsu Commission of Health between January 1 and March 20, 2020. MATERIAL AND METHODS We conducted an epidemiological investigation enrolling 631 patients with laboratory-confirmed COVID-19 from our clinic from January to March 2020. Patients' information was collected through a standard questionnaire. Then, we described the patients' epidemiological characteristics, analyzed risk factors associated with disease severity, and assessed causes of zero mortality. Additionally, some key technologies for epidemic prevention and control were identified. RESULTS Of the 631 patients, 8.46% (n=53) were severe cases, and no deaths were recorded (n=0). The epidemic of COVID-19 has gone through 4 stages: a sporadic phase, an exponential growth phase, a peak plateau phase, and a declining phase. The proportion of severe cases was significantly different among the 4 stages and 13 municipal prefectures (P<0.001). Factors including age >65 years old, underlying medical conditions, highest fever >39.0°C, dyspnea, and lymphocytopenia (<1.0×10⁹/L) were early warning signs of disease severity (P<0.05). In contrast, earlier clinic visits were associated with better patient outcomes (P=0.029). Further, the viral load was a potentially useful marker associated with COVID-19 infection severity. CONCLUSIONS The study findings from the beginning of the COVID-19 epidemic in Jiangsu Province, China showed that patients who were more than 65 years of age and with comorbidities and presented with a fever of more than 39.0°C developed more severe disease. However, mortality was prevented in this initial patient population by early supportive clinical management.
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http://dx.doi.org/10.12659/MSM.929986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059346PMC
April 2021

Changes in electroencephalographic power and bicoherence spectra according to depth of dexmedetomidine sedation in patients undergoing spinal anesthesia.

Int J Med Sci 2021 15;18(10):2117-2127. Epub 2021 Mar 15.

Division of Oncology, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.

Assessment the depth of dexmedetomidine sedation using electroencephalographic (EEG) features can improve the quality of procedural sedation. Previous volunteer studies of dexmedetomidine-induced EEG changes need to be validated, and changes in bicoherence spectra during dexmedetomidine sedation has not been revealed yet. We aimed to investigate the dexmedetomidine-induced EEG change using power spectral and bicoherence analyses in the clinical setting. Thirty-six patients undergoing orthopedic surgery under spinal anesthesia were enrolled in this study. Dexmedetomidine sedation was conducted by the stepwise increase in target effect site concentration (Ce) while assessing sedation levels. Bispectral index (BIS) and frontal electroencephalography were recorded continuously, and the performance of BIS and changes in power and bicoherence spectra were analyzed with the data from the F3 electrode. The prediction probability values for detecting different sedation levels were 0.847, 0.841, and 0.844 in BIS, 95% spectral edge frequency, and dexmedetomidine Ce, respectively. As the depth of sedation increased, δ power increased, but high β and γ power decreased significantly ( <0.001). α and spindle power increased significantly under light and moderate sedation ( <0.001 in light vs baseline and deep sedation; = 0.002 and <0.001 in moderate sedation vs baseline and deep sedation, respectively). The bicoherence peaks of the δ and α-spindle regions along the diagonal line of the bicoherence matrix emerged during moderate and deep sedation. Peak bicoherence in the δ area showed sedation-dependent increases (29.93%±7.38%, 36.72%±9.70%, 44.88%±12.90%; light, moderate, and deep sedation; = 0.008 and <0.001 in light sedation vs moderate and deep sedation, respectively; = 0.007 in moderate sedation vs deep sedation), whereas peak bicoherence in the α-spindle area did not change (22.92%±4.90%, 24.72%±4.96%, and 26.96%±8.42%, respectively; =0.053). The increase of δ power and the decrease of high-frequency power were associated with the gradual deepening of dexmedetomidine sedation. The δ bicoherence peak increased with increasing sedation level and can serve as an indicator reflecting dexmedetomidine sedation levels.
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http://dx.doi.org/10.7150/ijms.54677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040410PMC
March 2021

Correction to: Risk of progression of idiopathic pulmonary fibrosis to connective tissue disease: a long-term observational study in 527 patients.

Clin Rheumatol 2021 Jun;40(6):2525

Division of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

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http://dx.doi.org/10.1007/s10067-021-05732-5DOI Listing
June 2021
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