Publications by authors named "Dong Hyun Kim"

1,733 Publications

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Hyperoside improves learning and memory deficits by amyloid β in mice through regulating synaptic calcium-permeable AMPA receptors.

Eur J Pharmacol 2022 Aug 7:175188. Epub 2022 Aug 7.

Department of Pharmacology and Department of Advanced Translational Medicine, School of Medicine, Konkuk University, Seoul, 05029, Republic of Korea. Electronic address:

Alzheimer's disease (AD) is the most common degenerative disease and is indicative of dementia. The cerebral accumulation of amyloid β (Aβ), a crucial factor in AD, initiates synaptic and cognitive dysfunction. Therefore, the elevation of synaptic and cognitive functions may help manage dementia in AD. In this study, we suggest hyperoside as a synaptic function- and memory-enhancing agent. Hyperoside enhanced learning and memory in passive avoidance and object recognition tasks. Hyperoside facilitated synaptic long-term potentiation (LTP) in acute hippocampal slices. IEM-1460, a calcium-permeable amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (CP-AMPAR) antagonist, blocked the facilitation effect of hyperoside. Hyperoside also induced N-methyl-d-aspartate receptor (NMDAR)-independent LTP, which was blocked by IEM-1460, suggesting the involvement of CP-AMPARs in the synaptic effects of hyperoside-mediated LTP. PKI (a PKA inhibitor) or SQ22536 (adenylyl cyclase, an AC inhibitor) blocked hyperoside-facilitated LTP and hyperoside-induced NMDAR-independent LTP. Hyperoside-enhanced learning and memory were blocked by IEM-1460, suggesting the involvement of CP-AMPARs in the effect of hyperoside on learning and memory. Finally, hyperoside ameliorated Aβ-induced memory impairments in an AD mouse model. These results suggest that hyperoside enhances learning and memory, and this may be due to the effect of CP-AMPARs.
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http://dx.doi.org/10.1016/j.ejphar.2022.175188DOI Listing
August 2022

Comprehensive lipid and lipid-related gene investigations of host immune responses to characterize metabolism-centric biomarkers for pulmonary tuberculosis.

Sci Rep 2022 Aug 4;12(1):13395. Epub 2022 Aug 4.

Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.

Despite remarkable success in the prevention and treatment of tuberculosis (TB), it remains one of the most devastating infectious diseases worldwide. Management of TB requires an efficient and timely diagnostic strategy. In this study, we comprehensively characterized the plasma lipidome of TB patients, then selected candidate lipid and lipid-related gene biomarkers using a data-driven, knowledge-based framework. Among 93 lipids that were identified as potential biomarker candidates, ether-linked phosphatidylcholine (PC O-) and phosphatidylcholine (PC) were generally upregulated, while free fatty acids and triglycerides with longer fatty acyl chains were downregulated in the TB group. Lipid-related gene enrichment analysis revealed significantly altered metabolic pathways (e.g., ether lipid, linolenic acid, and cholesterol) and immune response signaling pathways. Based on these potential biomarkers, TB patients could be differentiated from controls in the internal validation (random forest model, area under the curve [AUC] 0.936, 95% confidence interval [CI] 0.865-0.992). PC(O-40:4), PC(O-42:5), PC(36:0), and PC(34:4) were robust biomarkers able to distinguish TB patients from individuals with latent infection and healthy controls, as shown in the external validation. Small changes in expression were identified for 162 significant lipid-related genes in the comparison of TB patients vs. controls; in the random forest model, their utilities were demonstrated by AUCs that ranged from 0.829 to 0.956 in three cohorts. In conclusion, this study introduced a potential framework that can be used to identify and validate metabolism-centric biomarkers.
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http://dx.doi.org/10.1038/s41598-022-17521-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352691PMC
August 2022

Deep Radiomics-based Approach to the Diagnosis of Osteoporosis Using Hip Radiographs.

Radiol Artif Intell 2022 Jul 25;4(4):e210212. Epub 2022 May 25.

Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea (S.K., H.D.C., S.H.H., J.Y.C., H.J.Y.); Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea (B.R.K.); Department of Nuclear Engineering, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea (J.L.); Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea (S.J.Y.); Department of Radiology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea (D.H.K.); Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea (S.J.Y., S.H.H., J.Y.C., H.J.Y.); and Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea (S.H.H.).

Purpose: To develop and validate deep radiomics models for the diagnosis of osteoporosis using hip radiographs.

Materials And Methods: A deep radiomics model was developed using 4924 hip radiographs from 4308 patients (3632 women; mean age, 62 years ± 13 [SD]) obtained between September 2009 and April 2020. Ten deep features, 16 texture features, and three clinical features were used to train the model. T score measured with dual-energy x-ray absorptiometry was used as a reference standard for osteoporosis. Seven deep radiomics models that combined different types of features were developed: clinical (model C); texture (model T); deep (model D); texture and clinical (model TC); deep and clinical (model DC); deep and texture (model DT); and deep, texture, and clinical features (model DTC). A total of 444 hip radiographs obtained between January 2019 and April 2020 from another institution were used for the external test. Six radiologists performed an observer performance test. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic performance.

Results: For the external test set, model D (AUC, 0.92; 95% CI: 0.89, 0.95) demonstrated higher diagnostic performance than model T (AUC, 0.77; 95% CI: 0.70, 0.83; adjusted < .001). Model DC (AUC, 0.95; 95% CI: 0.92, 0.97; adjusted = .03) and model DTC (AUC, 0.95; 95% CI: 0.92, 0.97; adjusted = .048) showed improved diagnostic performance compared with model D. When observer performance without and with the assistance of the model DTC prediction was compared, performance improved from a mean AUC of 0.77 to 0.87 ( = .002).

Conclusion: Deep radiomics models using hip radiographs could be used to diagnose osteoporosis with high performance. Skeletal-Appendicular, Hip, Absorptiometry/Bone Densitometry© RSNA, 2022.
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http://dx.doi.org/10.1148/ryai.210212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344212PMC
July 2022

Three-Dimensional Visualization of Postsurgical Airway Changes Using 3D Printing Technology in a Patient With Mandibular Prognathism: A 5-Year Follow-up Study.

J Craniofac Surg 2022 Jul 27. Epub 2022 Jul 27.

Department of Orthodontics, School of Dentistry, Chonnam National University, Gwangju, Korea.

This case-report described the 3-dimensional (3D) evaluation of airway changes using 3D printing technology in a patient with mandibular prognathism, treated via mandibular setback surgery with maxillary posterior impaction. The airway dimensions, following orthognathic surgery, were printed using 3D printing technology and the sequential airway changes were visualized. The patient underwent orthognathic surgery for the correction of mandibular prognathism. Five years later, the airway changes were visualized and evaluated using rapid prototyping. The 3D visualization of the airway changes following surgery alerted clinicians of patients with mandibular prognathism and facilitated effective communication with their patients. This case-report documented the long-term evaluation and visualization of the postoperative airway changes in patients with mandibular prognathism using cone-beam computed tomography and 3D printing technology.
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http://dx.doi.org/10.1097/SCS.0000000000008789DOI Listing
July 2022

Citation: Tight Junction Protein Expression-Inducing Probiotics Alleviate TNBS-Induced Cognitive Impairment with Colitis in Mice.

Nutrients 2022 Jul 20;14(14). Epub 2022 Jul 20.

Neurobiota Research Center, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.

A leaky gut is closely connected with systemic inflammation and psychiatric disorder. The rectal injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS) induces gut inflammation and cognitive function in mice. Therefore, we selected NK219, NK209, and NK210, which induced claudin-1 expression in TNBS- or lipopolysaccharide (LPS)-stimulated Caco-2 cells, from the fecal bacteria collection of humans and investigated their effects on cognitive function and systemic inflammatory immune response in TNBS-treated mice. The intrarectal injection of TNBS increased cognitive impairment-like behaviors in the novel object recognition and Y-maze tests, TNF-α, IL-1β, and IL-17 expression in the hippocampus and colon, and LPS level in the blood and feces, while the expression of hippocampal claudin-5 and colonic claudin-1 decreased. Oral administration of NK209, NK210, and NK219 singly or together decreased TNBS-impaired cognitive behaviors, TNF-α and IL-1β expression, NF-κBIba1 cell and LPSIba1 cell numbers in the hippocampus, and LPS level in the blood and feces, whereas BDNFNeuN cell and claudin-5 cell numbers and IL-10 expression increased. Furthermore, they suppressed TNBS-induced colon shortening and colonic TNF-α and IL-1β expression, while colonic IL-10 expression and mucin protein-2 cell and claudin-1 cell numbers expression increased. Of these, NK219 most strongly alleviated cognitive impairment and colitis. They additively alleviated cognitive impairment with colitis. Based on these findings, NK209, NK210, NK219, and their combinations may alleviate cognitive impairment with systemic inflammation by suppressing the absorption of gut bacterial products including LPS into the blood through the suppression of gut bacterial LPS production and alleviation of a leaky gut by increasing gut tight junction proteins and mucin-2 expression.
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http://dx.doi.org/10.3390/nu14142975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317072PMC
July 2022

Evaporation of As and Sn from Liquid Iron: Experiments and a Kinetic Model during Top-Blown Oxygen Steelmaking Process.

Materials (Basel) 2022 Jul 7;15(14). Epub 2022 Jul 7.

Graduate Institute of Ferrous & Energy Materials Technology, Pohang University of Science and Technology, Pohang 37673, Gyeongbuk, Korea.

Evaporation kinetics of tramp elements (M = As and Sn) in liquid iron were investigated by high-temperature gas-liquid reaction experiments and a phenomenological kinetic model. Residual content of As or Sn in the liquid iron ([pct M]) during the evaporation was measured in the temperature range of 1680 °C to 1760 °C. [pct As] and [pct Sn] decreased faster as the reaction temperature and [pct C]0 increased. Assuming first-order reaction kinetics, the apparent rate constants (kM) were obtained at each reaction temperature and [pct C]0. [pct M] in a liquid iron during the top-blown oxygen steelmaking process was simulated, with an emphasis on enlarging the reaction surface area by forming a large number of liquid iron droplets. The surface area and the droplet generation rate were obtained based on the oxygen-blowing condition. The whole surface area increased up to ∼163 times the initial liquid iron (bath) surface area, due to the generation of the droplets. Using the kM obtained in the present study, the evaporation of M during the top-blown oxygen steelmaking process for 200 tonnes of liquid iron was simulated. For a condition of [pct M]0 = 0.005 (M = As and Sn), As and Sn could be removed from the liquid iron, which was seen to be much improved by the consideration of the droplet generation. However, additional actions are required to improve the evaporation rate, as the evaporation rate in the BOF process was not fast enough to be practically considered.
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http://dx.doi.org/10.3390/ma15144771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9323924PMC
July 2022

Distinct subsets of innate lymphoid cells in nasal polyp.

Allergol Int 2022 Jul 19. Epub 2022 Jul 19.

Department of Otorhinolaryngology - Head and Neck Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address:

Background: Group 2 innate lymphoid cells (ILC2s) contribute to the pathogenesis of eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNPs). However, the role of other subsets of ILCs and the differentiation of ILCs in CRSwNPs is not well understood. This study aimed to characterize the ILC subsets and evaluate the differentiation of ILCs from ILC precursors (ILCPs) in NP tissue.

Methods: ILC subsets and ILCPs were evaluated by flow cytometry in fresh sinonasal mucosa from patients with CRSwNPs and control subjects. Subsets were compared based on clinical variables and immunological features of the patients. Sorted ILCPs (LinCD127CD117CD45RAIL1R1) were cultured with cytokines.

Results: The frequency of ILC1s and IFN-γ-producing ILC1s increased in non-eosinophilic NPs, whereas that of ILC2s and IL-5-producing ILC2s increased in eosinophilic NPs, particularly in patients with comorbid asthma. The frequency of ILC1s and IFN-γ-producing ILC1s, and frequency of ILC2s and IL-5-producing ILC2s positively correlated with that of neutrophils and eosinophils, respectively. The proportion of IFN-γ-producing ILC1s positively correlated with clinical severity and levels of IFN-γ and IL-8. The proportion of IL-5-producing ILC2s positively correlated with levels of IL-5, CCL24, and total IgE. ILCPs were identified in NP tissue and differentiated into IFN-γ-producing or IL-5-producing ILCs in response to increased IL-12 and IL-18 or IL-25 and IL-33 in non-eosinophilic NPs and eosinophilic NPs, respectively.

Conclusions: ILC1s and ILC2s may be associated with neutrophilic and eosinophilic inflammation in CRSwNPs, respectively. In addition, ILCPs located in the sinus mucosa could differentiate into IFN-γ- or IL-5-producing cells in response to local cytokine stimuli.
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http://dx.doi.org/10.1016/j.alit.2022.06.007DOI Listing
July 2022

Genome-wide gene expression analysis reveals molecular insights into the drug-induced toxicity of nephrotoxic agents.

Life Sci 2022 Jul 16;306:120801. Epub 2022 Jul 16.

Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan 614-735, Republic of Korea; Center for Personalized Precision Medicine of Tuberculosis, Inje University College of Medicine, Busan 614-735, Republic of Korea. Electronic address:

Drug-induced nephrotoxicity is frequently reported. However, the mechanisms underlying nephrotoxic medications and their overlapping molecular events, which might have therapeutic value, are unclear. We performed a genome-wide analysis of gene expression and a gene set enrichment analysis to identify common and unique pathways associated with the toxicity of colistin, ifosfamide, indomethacin, and puromycin. Rats were randomly allocated into the treatment or control group. The treatment group received a toxic dose once daily of each investigated drug for 1 week. Differentially expressed genes were found in the drug-treated kidney and liver compared to the control, except for colistin in the liver. Upregulated pathways were mainly related to cell death, cell cycle, protein synthesis, and immune response modulation in the kidney. Cell cycle was upregulated by all drugs. Downregulated pathways were associated with carbon metabolism, amino acid metabolism, and fatty acid metabolism. Indomethacin, colistin, and puromycin shared the most altered pathways in the kidney. Ifosfamide and indomethacin affected molecular processes greatly in the liver. Our findings provide insight into the mechanisms underlying the renal and hepatic adverse effects of the four drugs. Further investigation should explore the combinatory drug therapies that attenuate the toxic effects and maximize the effectiveness of nephrotoxic drugs.
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http://dx.doi.org/10.1016/j.lfs.2022.120801DOI Listing
July 2022

Cooperative hand therapy via a soft, wearable, and unilateral telerobotic system.

IEEE Trans Biomed Eng 2022 Jul 18;PP. Epub 2022 Jul 18.

Functional rehabilitation of the hand is a complex and difficult process involving a large number of degrees of freedom (DOFs). Soft wearable hand-rehabilitation robots have assisted hand movements with a compact structural design, but effective rehabilitation requires an intuitive control scheme that can manage many DOFs and incorporate interaction with an occupational therapist, which has yet to be developed for this type of device. Thus, we present a soft wearable unilateral telerobotic system that enables various grasping tasks and cooperative interaction between the patient and therapist. The presented system consists of a sensor glove that measures the hand postures of the occupational therapist and a soft robotic glove that assists 4-DOF movements of the patient's hand, including adjustments of the interjoint coordination of the finger and 2-DOF movements of the thumb (flexion/extension and opposition/reposition). The soft robotic glove effectuates hand movements based on the measurements from the sensor glove. A telerobotic impedance-control scheme provides intuitive guidance of various hand postures, along with a fingertip-force vector. The feasible workspace and control performance of the system were evaluated on a healthy recruit and a poststroke patient. The presented system allowed the therapist to increase the patient's thumb workspace by 400% in palmar-dorsal direction and to control the fingertip-force direction at -30°∼10° range by enabling control of interjoint coordination of the proximal-interphalangeal and metacarpophalangeal joints. These features facilitate patients to perform various postures for stable object grasping. The presented rehabilitation system is suitable for noncontact telehealthcare that facilitates patient-therapist interactions.
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http://dx.doi.org/10.1109/TBME.2022.3191690DOI Listing
July 2022

Calcipotriol/betamethasone aerosol foam (Enstilum) for the topical treatment of psoriasis vulgaris in routine practice in Korea: A prospective, noninterventional, multicenter study of treatment outcomes and patient satisfaction.

J Dermatol 2022 Jul 18. Epub 2022 Jul 18.

Department of Dermatology, Seoul National University College of Medicine, and Seoul National University Bundang Hospital, Seongnam, South Korea.

An innovative foam formulation for the fixed-dose combination of calcipotriol and betamethasone dipropionate (Cal/BD) has recently become available for the treatment of psoriasis vulgaris. Observational studies of patients treated with Cal/BD foam in routine practice have been conducted in several Western countries, but there are limited data on outcomes in Asian patients. We performed a prospective, open-label, noncomparative, noninterventional study to investigate treatment outcomes and satisfaction in adult patients receiving Cal/BD foam for psoriasis vulgaris in dermatological centers and outpatient clinics in Korea. Data were collected at the time of enrollment (Visit 1) and at a routine clinic visit ~4 weeks later (Visit 2). In total, 218 patients were enrolled, of whom 175 were included in the safety analysis set (58.9% male; mean age ± standard deviation 46.7 ± 15.1 years; use of Cal/BD foam at least once daily 74.3%). Of the safety analysis set, 166 patients had at least mild psoriasis (Investigator Global Assessment [IGA] ≥ 2) and were analyzed for treatment outcomes and satisfaction. Of the 166 patients, 71.7% had mild psoriasis (IGA 2) at baseline. The majority (57.8%) achieved an IGA of 0/1 (clear/almost clear) at Visit 2. The Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI) showed significant improvements from Visit 1 to Visit 2 (PASI -2.4 ± 3.0, DLQI -4.5 ± 5.2, both P < 0.0001). Most of the patients were satisfied with the Cal/BD foam treatment; 77.0%, 60.0%, and 73.9% were satisfied in terms of effectiveness, ease of use, and global satisfaction, respectively. In the safety analysis set, adverse events were reported in 13 patients (7.4%). In conclusion, this first Korean real-world study of Cal/BD foam shows improvement of lesions and health-related quality of life after 4 weeks of treatment, with high global satisfaction and good overall tolerability and safety.
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http://dx.doi.org/10.1111/1346-8138.16519DOI Listing
July 2022

Physicochemically Constructed Unidirectional Aluminum Bismuth Gallium Zinc Oxide Film for Enhanced Nematic Liquid Crystal System Using a Brush-Coating Method.

Chemphyschem 2022 Jul 7:e202200263. Epub 2022 Jul 7.

IT Nano Electronic Device Laboratory, Department of Electrical and Electronic Engineering, Yonsei University, Seodaemun-gu, 120-749, Seoul, South Korea.

We propose a convenient brush coating method for liquid crystal (LC) alignment. This method enables film deposition and an alignment layer treatment process simultaneously. Aluminum bismuth gallium zinc oxide (AlBiGaZnO) is used as the alignment layer. After the curing process, a unidirectional AlBiGaZnO film is formed; its surface morphology and chemical composition were verified using scanning electron microscopy and X-ray photoelectron spectroscopy. This oriented structure of the surface was produced by shear-stress which originated from brush movement. That structure induced a surface anisotropic characteristic and resulted in a uniform LC alignment. The uniform and homogeneous LC alignment state on the film was confirmed using polarized optical microscopy and pre-tilt angle analysis. The brush coated AlBiGaZnO film exhibited excellent thermal budget for advanced LC system. The film exhibited enhanced electro-optical performance with a low operating voltage. These results demonstrate the potential of LC alignment technology via the brush coating method.
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http://dx.doi.org/10.1002/cphc.202200263DOI Listing
July 2022

Ensemble deep learning model for predicting anterior cruciate ligament tear from lateral knee radiograph.

Skeletal Radiol 2022 Jun 9. Epub 2022 Jun 9.

Armed Forces Yangju Hospital, Yangju, Republic of Korea.

Objective: To develop an ensemble deep learning model (DLM) predicting anterior cruciate ligament (ACL) tears from lateral knee radiographs and to evaluate its diagnostic performance.

Materials And Methods: In this study, 1433 lateral knee radiographs (661 with ACL tear confirmed on MRI, 772 normal) from two medical centers were split into training (n = 1146) and test sets (n = 287). Three single DLMs respectively classifying radiographs with ACL tears, abnormal lateral femoral notches, and joint effusion were developed. An ensemble DLM predicting ACL tears was developed by combining the three DLMs via stacking method. The sensitivities, specificities, and area under the receiver operating characteristic curves (AUCs) of the DLMs and three radiologists were compared using McNemar test and Delong test. Subgroup analysis was performed to identify the radiologic features associated with the sensitivity.

Results: The sensitivity, specificity, and AUC of the ensemble DLM were 86.8% (95% confidence interval [CI], 79.9-92.0%), 89.4% (95% CI, 83.4-93.8%), and 0.927 (95% CI, 0.891-0.954), achieving diagnostic performance comparable with that of a musculoskeletal radiologist (P = 0.193, McNemar test; P = 0.131, Delong test). The AUC of the ensemble DLM was significantly higher than those of non-musculoskeletal radiologists (P = 0.043, P < 0.001). The sensitivity of the DLM was higher than that of the radiologists in the absence of an abnormal lateral femoral notch or joint effusion.

Conclusion: The diagnostic performance of the ensemble DLM in predicting lateral knee radiographs with ACL tears was comparable to that of a musculoskeletal radiologist.
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http://dx.doi.org/10.1007/s00256-022-04081-xDOI Listing
June 2022

Anticancer effect of verteporfin on non-small cell lung cancer via downregulation of ANO1.

Biomed Pharmacother 2022 Jul 1;153:113373. Epub 2022 Jul 1.

New Drug Development Center, Daegu Gyeongbuk Medical Innovation Foundation, Daegu, the Republic of Korea. Electronic address:

Anoctamin 1 (ANO1) is a calcium-activated chloride channel found in various cell types and is overexpressed in non-small cell lung cancer (NSCLC), a major cause of cancer-related mortality. With the rising interest in development of druggable compounds for NSCLC, there has been a corresponding rise in interest in ANO1, a novel drug target for NSCLC. However, as ANO1 inhibitors that have been discovered simultaneously exhibit both the functions of an inhibition of ANO1 channel as well as a reduction of ANO1 protein levels, it is unclear which of the two functions directly causes the anticancer effect. In this study, verteporfin, a chemical compound that reduces ANO1 protein levels was identified through high-throughput screening. Verteporfin did not inhibit ANO1-induced chloride secretion but reduced ANO1 protein levels in a dose-dependent manner with an IC value of ~300 nM. Moreover, verteporfin inhibited neither P2Y receptor-induced intracellular Ca mobilization nor cystic fibrosis transmembrane conductance regulator (CFTR) channel activity, and molecular docking studies revealed that verteporfin bound to specific sites of ANO1 protein. Confirming that verteporfin reduces ANO1 protein levels, we then investigated the molecular mechanisms involved in its effect on NSCLC cells. Interestingly, verteporfin decreased ANO1 protein levels, the EGFR-STAT3 pathway as well as ANO1 mRNA expression. Verteporfin reduced the viability of ANO1-expressing cells (PC9, and gefitinib-resistant PC9) and induced apoptosis by increasing caspase-3 activity and PARP-1 cleavage. However, it did not affect hERG channel activity. These results show that the anticancer mechanism of verteporfin is caused via the down-regulation of ANO1.
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http://dx.doi.org/10.1016/j.biopha.2022.113373DOI Listing
July 2022

Apoferritin-Encapsulated Jerantinine A for Transferrin Receptor Targeting and Enhanced Selectivity in Breast Cancer Therapy.

ACS Omega 2022 Jun 13;7(25):21473-21482. Epub 2022 Jun 13.

School of Pharmacy, Biodiscovery Institute, The University of Nottingham, University Park, Nottingham NG7 2RD, U.K.

The O-acetyl (or acetate) derivative of the Aspidosperma alkaloid Jerantinine A (JAa) elicits anti-tumor activity against cancer cell lines including mammary carcinoma cell lines irrespective of receptor status (0.14 < GI < 0.38 μM), targeting microtubule dynamics. By exploiting breast cancer cells' upregulated transferrin receptor 1 (TfR1) expression and apoferritin (AFt) recognition, we sought to develop an AFt JAa-delivery vehicle to enhance tumor-targeting and reduce systemic toxicity. Optimizing pH-mediated reassembly, ∼120 JAa molecules were entrapped within AFt. Western blot and flow cytometry demonstrate TfR1 expression in cancer cells. Enhanced internalization of 5-carboxyfluorescein-conjugated human AFt in SKBR3 and MDA-MB-231 cancer cells is observed compared to MRC5 fibroblasts. Accordingly, AFt-JAa delivers significantly greater intracellular JAa levels to SKBR3 and MDA-MB-231 cells than naked JAa (0.2 μM) treatment alone. Compared to naked JAa (0.2 μM), AFt-JAa achieves enhanced growth inhibition (2.5-14-fold; <0.02 μM < GI < 0.15 μM) in breast cancer cells; AFt-JAa treatment results in significantly reduced clonal survival, more profound cell cycle perturbation including G2/M arrest, greater reduction in cell numbers, and increased apoptosis compared to the naked agent ( < 0.01). Decreased PLK1 and Mcl-1 expression, together with the appearance of cleaved poly (ADP-ribose)-polymerase, corroborate the augmented potency of AFt-JAa. Hence, we demonstrate that AFt represents a biocompatible vehicle for targeted delivery of JAa, offering potential to minimize toxicity and enhance JAa activity in TfR1-expressing tumors.
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http://dx.doi.org/10.1021/acsomega.2c00997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9244903PMC
June 2022

Metabolic modeling-based drug repurposing in Glioblastoma.

Sci Rep 2022 Jul 1;12(1):11189. Epub 2022 Jul 1.

Centre for Analytical Bioscience, Advanced Materials and Healthcare Technologies Division, School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, UK.

The manifestation of intra- and inter-tumor heterogeneity hinders the development of ubiquitous cancer treatments, thus requiring a tailored therapy for each cancer type. Specifically, the reprogramming of cellular metabolism has been identified as a source of potential drug targets. Drug discovery is a long and resource-demanding process aiming at identifying and testing compounds early in the drug development pipeline. While drug repurposing efforts (i.e., inspecting readily available approved drugs) can be supported by a mechanistic rationale, strategies to further reduce and prioritize the list of potential candidates are still needed to facilitate feasible studies. Although a variety of 'omics' data are widely gathered, a standard integration method with modeling approaches is lacking. For instance, flux balance analysis is a metabolic modeling technique that mainly relies on the stoichiometry of the metabolic network. However, exploring the network's topology typically neglects biologically relevant information. Here we introduce Transcriptomics-Informed Stoichiometric Modelling And Network analysis (TISMAN) in a recombinant innovation manner, allowing identification and validation of genes as targets for drug repurposing using glioblastoma as an exemplar.
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http://dx.doi.org/10.1038/s41598-022-14721-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249780PMC
July 2022

Farnesoid X receptor protects against cisplatin-induced acute kidney injury by regulating the transcription of ferroptosis-related genes.

Redox Biol 2022 08 23;54:102382. Epub 2022 Jun 23.

Department of Internal Medicine, Chonnam National University Medical School, Gwangju, 61469, South Korea. Electronic address:

The side effects of cisplatin, a widely used chemotherapeutic agent, include nephrotoxicity. Previous studies have reported that cisplatin induces ferroptosis and lipid peroxide accumulation. Ferroptosis, a type of regulated cell death, is characterized by iron-dependent lipid peroxidation. Although previous studies have examined the regulation of ferroptosis in acute kidney injury (AKI), the regulatory mechanism of ferroptosis has not been elucidated. Here, the ability of activated farnesoid X receptor (FXR) to attenuate cisplatin-induced AKI through the regulation of ferroptosis was examined. FXR deficiency exhibited more ferroptosis responses, such as increase in lipid peroxidation, iron content and heme oxygenase 1 protein, and a decrease in glutathione/glutathione disulfide ratio and glutathione peroxidase 4 levels in HK2 cells and mice. Increased blood urea nitrogen, serum creatinine, and ferroptotic responses in the cisplatin-induced AKI mouse model were mitigated upon treatment with the FXR agonist GW4064 but were exacerbated in FXR knockout mice. RNA sequencing analysis revealed that ferroptosis-associated genes were novel targets of FXR. FXR agonist upregulated the expression of lipid and glutathione metabolism-related genes and downregulated cell death-related genes. Additionally, chromatin immunoprecipitation assays, using mice renal tissues, revealed that agonist-activated FXR could bind to its known target genes (Slc51a, Slc51b, Osgin1, and Mafg) and ferroptosis-related genes (Aifm2, Ggt6, and Gsta4). Furthermore, activated FXR-dependent MAFG, a transcriptional repressor, could bind to Hmox1, Nqo1, and Tf in the renal tissues of FXR agonist-treated mice. These findings indicate that activated FXR regulates the transcription of ferroptosis-related genes and protects against cisplatin-induced AKI.
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http://dx.doi.org/10.1016/j.redox.2022.102382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9241134PMC
August 2022

Developing and validating polygenic risk scores for colorectal cancer risk prediction in East Asians.

Int J Cancer 2022 Jun 29. Epub 2022 Jun 29.

Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

Several polygenic risk scores (PRSs) have been developed to predict the risk of colorectal cancer (CRC) in European descendants. We used genome-wide association study (GWAS) data from 22 702 cases and 212 486 controls of Asian ancestry to develop PRSs and validated them in two case-control studies (1454 Korean and 1736 Chinese). Eleven PRSs were derived using three approaches: GWAS-identified CRC risk SNPs, CRC risk variants identified through fine-mapping of known risk loci and genome-wide risk prediction algorithms. Logistic regression was used to estimate odds ratios (ORs) and area under the curve (AUC). PRS , a PRS with 115 GWAS-reported risk variants derived from East-Asian data, validated significantly better than PRS derived from European descendants. In the Korea validation set, OR per SD increase of PRS was 1.63 (95% CI = 1.46-1.82; AUC = 0.63), compared with OR of 1.44 (95% CI = 1.29-1.60, AUC = 0.60) for PRS . PRS derived using meta-analysis results of both populations slightly improved the AUC to 0.64. Similar but weaker associations were found in the China validation set. Individuals among the highest 5% of PRS have a 2.52-fold elevated CRC risk compared with the medium (41-60th) risk group and have a 12% to 20% risk of developing CRC by age 85. PRSs constructed using results from fine-mapping and genome-wide algorithms did not perform as well as PRS and PRS in risk prediction, possibly due to a small sample size. Our results indicate that CRC PRSs are promising in predicting CRC risk in East Asians and highlights the importance of using population-specific data to build CRC risk prediction models.
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http://dx.doi.org/10.1002/ijc.34194DOI Listing
June 2022

Stacked U-Nets with self-assisted priors towards robust correction of rigid motion artifact in brain MRI.

Neuroimage 2022 Oct 23;259:119411. Epub 2022 Jun 23.

Department of Electrical and Electronic Engineering, College of Engineering, Yonsei University, Seoul, South Korea. Electronic address:

Magnetic Resonance Imaging (MRI) is sensitive to motion caused by patient movement due to the relatively long data acquisition time. This could cause severe degradation of image quality and therefore affect the overall diagnosis. In this paper, we develop an efficient retrospective 2D deep learning method called stacked U-Nets with self-assisted priors to address the problem of rigid motion artifacts in 3D brain MRI. The proposed work exploits the usage of additional knowledge priors from the corrupted images themselves without the need for additional contrast data. The proposed network learns the missed structural details through sharing auxiliary information from the contiguous slices of the same distorted subject. We further design a refinement stacked U-Nets that facilitates preserving the spatial image details and improves the pixel-to-pixel dependency. To perform network training, simulation of MRI motion artifacts is inevitable. The proposed network is optimized by minimizing the loss of structural similarity (SSIM) using the synthesized motion-corrupted images from 83 real motion-free subjects. We present an intensive analysis using various types of image priors: the proposed self-assisted priors and priors from other image contrast of the same subject. The experimental analysis proves the effectiveness and feasibility of our self-assisted priors since it does not require any further data scans. The overall image quality of the motion-corrected images via the proposed motion correction network significantly improves SSIM from 71.66% to 95.03% and declines the mean square error from 99.25 to 29.76. These results indicate the high similarity of the brain's anatomical structure in the corrected images compared to the motion-free data. The motion-corrected results of both the simulated and real motion data showed the potential of the proposed motion correction network to be feasible and applicable in clinical practices.
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http://dx.doi.org/10.1016/j.neuroimage.2022.119411DOI Listing
October 2022

Structural and Functional Validation of a Full-Thickness Self-Assembled Skin Equivalent for Disease Modeling.

Pharmaceutics 2022 Jun 7;14(6). Epub 2022 Jun 7.

Department of Dermatology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13497, Korea.

Recently, various types of in vitro-reconstructed 3D skin models have been developed for drug testing and disease modeling. Herein, we structurally and functionally validated a self-assembled reconstructed skin equivalent (RSE) and developed an IL-17a-induced in vitro psoriasis-like model using a self-assembled RSE. The tissue engineering approach was used to construct the self-assembled RSE. The dermal layer was generated using fibroblasts secreting their own ECM, and the epidermal layer was reconstructed by seeding keratinocytes on the dermal layer. To generate the psoriatic model, IL-17A was added to the culture medium during the air-liquid interface culture period. Self-assembled RSE resulted in a fully differentiated epidermal layer, a well-established basement membrane, and dermal collagen deposition. In addition, self-assembled RSE was tested for 20 reference chemicals according to the Performance Standard of OECD TG439 and showed overall sensitivity, specificity, and accuracy of 100%, 90%, and 95%, respectively. The IL-17a-treated psoriatic RSE model exhibited psoriatic epidermal characteristics, such as epidermal hyperproliferation, parakeratosis, and increased expression of KRT6, KRT17, hBD2, and S100A9. Thus, our results suggest that a self-assembled RSE that structurally and functionally mimics the human skin has a great potential for testing various drugs or cosmetic ingredients and modeling inflammatory skin diseases.
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http://dx.doi.org/10.3390/pharmaceutics14061211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231172PMC
June 2022

Alternative splicing variant of NRP/B promotes tumorigenesis of gastric cancer.

BMB Rep 2022 Jul;55(7):348-353

Department of Biochemistry, Institution of Basic Medical Science, School of Medicine, CHA University, Seongnam 13488; Department of Dermatology, Bundang CHA Medical Center, School of Medicine, CHA University, Seongnam 13496, Korea.

Gastrointestinal cancer is associated with a high mortality rate. Here, we report that the splice variant of NRP/B contributes to tumorigenic activity in highly malignant gastric cancer through dissociation from the tumor repressor, HDAC5. NRP/B mRNA expression is significantly higher in the human gastric cancer tissues than in the normal tissues. Further, high levels of both the NRP/B splice variant and Lgr5, but not the full-length protein, are found in highly tumorigenic gastric tumor cells, but not in non-tumorigenic cells. The loss of NRP/B markedly inhibits cell migration and invasion, which reduces tumor formation in vivo. Importantly, the inhibition of alternative splicing increases the levels of NRP/B-1 mRNA and protein in AGS cells. The ectopic expression of full-length NRP/B exhibits tumor-suppressive activity, whereas NRP/B-2 induces the noninvasive human gastric cancer cells tumorigenesis. The splice variant NRP/B-2 which loses the capacity to interact with tumor repressors promoted oncogenic activity, suggesting that the BTB/POZ domain in the N-terminus has a crucial role in the suppression of gastric cancer. Therefore, the regulation of alternative splicing of the NRP/B gene is a potential novel target for the treatment of gastrointestinal cancer. [BMB Reports 2022; 55(7): 348-353].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340087PMC
July 2022

Single-Cell Metabolic Profiling of Macrophages Using 3D OrbiSIMS: Correlations with Phenotype.

Anal Chem 2022 07 17;94(26):9389-9398. Epub 2022 Jun 17.

Advanced Materials and Healthcare Technologies Division, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom.

Macrophages are important immune cells that respond to environmental cues acquiring a range of activation statuses represented by pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes at each end of their spectrum. Characterizing the metabolic signature (metabolic profiling) of different macrophage subsets is a powerful tool to understand the response of the human immune system to different stimuli. Here, the recently developed 3D OrbiSIMS instrument is applied to yield useful insight into the metabolome from individual cells after in vitro differentiation of macrophages into naïve, M1, and M2 phenotypes using different cytokines. This analysis strategy not only requires more than 6 orders of magnitude less sample than traditional mass spectrometry approaches but also allows the study of cell-to-cell variance. Characteristic metabolites in macrophage subsets are identified using a targeted lipid and data-driven multivariate approach highlighting amino acids and other small molecules. The diamino acids alanylasparagine and lipid sphingomyelin SM(d18/16:0) are uniquely found in M1 macrophages, while pyridine and pyrimidine are observed at increased intensity in M2 macrophages, findings which link to known biological pathways. The first demonstration of this capability illustrates the great potential of direct cell analysis for in situ metabolite profiling with the 3D OrbiSIMS to probe functional phenotype at the single-cell level using molecular signatures and to understand the response of the human body to implanted devices and immune diseases.
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http://dx.doi.org/10.1021/acs.analchem.2c01375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260720PMC
July 2022

Efficient Photon Extraction in Top-Emission Organic Light-Emitting Devices Based on Ampicillin Microstructures.

Adv Mater 2022 Aug 11;34(32):e2202866. Epub 2022 Jul 11.

Division of Display and Semiconductor Physics, Display Convergence, College of Science and Technology, Korea University Sejong Campus, 2511 Sejong-ro, Sejong City, 30019, Republic of Korea.

The desire to enhance the efficiency of organic light-emitting devices (OLEDs) has driven to the investigation of advanced materials with fascinating properties. In this work, the efficiency of top-emission OLEDs (TEOLEDs) is enhanced by introducing ampicillin microstructures (Amp-MSs) with dual phases (α-/β-phase) that induce photoluminescence (PL) and electroluminescence (EL). Moreover, Amp-MSs can adjust the charge balance by Fermi level (E ) alignment, thereby decreasing the leakage current. The decrease in the wave-guided modes can enhance the light outcoupling through optical scattering. The resulting TEOLED demonstrates a record-high external quantum efficiency (EQE) (maximum: 68.7% and average: 63.4% at spectroradiometer; maximum: 44.8% and average: 42.6% at integrating sphere) with a wider color gamut (118%) owing to the redshift of the spectrum by J-aggregation. Deconvolution of the EL intensities is performed to clarify the contribution of Amp-MSs to the device EQE enhancement (optical scattering by Amp-MSs: 17.0%, PL by radiative energy transfer: 9.1%, and EL by J-aggregated excitons: 4.6%). The proposed TEOLED outperforms the existing frameworks in terms of device efficiency.
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http://dx.doi.org/10.1002/adma.202202866DOI Listing
August 2022

Graphene-Based Intrinsically Stretchable 2D-Contact Electrodes for Highly Efficient Organic Light-Emitting Diodes.

Adv Mater 2022 Aug 1;34(31):e2203040. Epub 2022 Jul 1.

Department of Materials Science and Engineering, Seoul National University, Seoul, 08826, Republic of Korea.

Intrinsically stretchable organic light-emitting diodes (ISOLEDs) are becoming essential components of wearable electronics. However, the efficiencies of ISOLEDs have been highly inferior compared with their rigid counterparts, which is due to the lack of ideal stretchable electrode materials that can overcome the poor charge injection at 1D metallic nanowire/organic interfaces. Herein, highly efficient ISOLEDs that use graphene-based 2D-contact stretchable electrodes (TCSEs) that incorporate a graphene layer on top of embedded metallic nanowires are demonstrated. The graphene layer modifies the work function, promotes charge spreading, and impedes inward diffusion of oxygen and moisture. The work function (WF) of 3.57 eV is achieved by forming a strong interfacial dipole after deposition of a newly designed conjugated polyelectrolyte with crown ether and anionic sulfonate groups on TCSE; this is the lowest value ever reported among ISOLEDs, which overcomes the existing problem of very poor electron injection in ISOLEDs. Subsequent pressure-controlled lamination yields a highly efficient fluorescent ISOLED with an unprecedently high current efficiency of 20.3 cd A , which even exceeds that of an otherwise-identical rigid counterpart. Lastly, a 3 inch five-by-five passive matrix ISOLED is demonstrated using convex stretching. This work can provide a rational protocol for designing intrinsically stretchable high-efficiency optoelectronic devices with favorable interfacial electronic structures.
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http://dx.doi.org/10.1002/adma.202203040DOI Listing
August 2022

Mucosal associated invariant T cells in ARDS: MAIT cells set fire to macrophages via cytokines.

Thorax 2022 Jun 10. Epub 2022 Jun 10.

Laboratory of Autoimmunity and Inflammation (LAI), Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea

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http://dx.doi.org/10.1136/thoraxjnl-2022-218696DOI Listing
June 2022

Enhanced systemic antilymphoma immune response by photothermal therapy with CpG deoxynucleotide-coated nanoparticles.

Blood Adv 2022 08;6(15):4581-4592

Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.

In preclinical studies, we investigated a novel mechanism of in situ vaccination in lymphoma. Radiation therapy (RT) can induce abscopal responses in lymphoma models, but this has not translated into clinical efficacy. We hypothesized that immune stimulation with cytosine guanine dinucleotide (CpG) deoxynucleotides could enhance abscopal effects induced by RT or photothermal therapy (PTT), which has been shown to have an immune stimulatory effect in solid tumors but has not been studied in lymphoma. We designed a branched gold nanoparticle (NP) platform to carry CpG deoxynucleotides while maintaining PTT function and compared the immunologic profile of the tumor microenvironment after PTT or RT in a dual-flank lymphoma model. One flank was treated with CpG deoxynucleotides with RT or PTT, and the other tumor was left untreated. We found that the CpG deoxynucleotide/PTT group had significant reduction in growth in both treated (primary) and untreated (secondary) tumors, suggesting an improved abscopal response, with a concomitant increase in CD8/CD4 and cytotoxic T-cell/regulatory T-cell ratios in both primary and secondary tumors compared with CpG deoxynucleotides/RT. Dendritic cells in primary and secondary draining lymph nodes had increased maturation markers in the CpG deoxynucleotide/PTT group, and the effector memory T cells (both CD4 and CD8) in the secondary tumor and spleen were increased, suggesting a systemic vaccination effect. These data suggest that in a lymphoma model, PTT using a CpG deoxynucleotide NP platform resulted in enhanced in situ vaccination and abscopal response compared with RT.
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http://dx.doi.org/10.1182/bloodadvances.2022008040DOI Listing
August 2022

Microalgae Bioactive Compounds to Topical Applications Products-A Review.

Molecules 2022 May 30;27(11). Epub 2022 May 30.

School of Engineering and Sciences, Tecnológico de Monterrey, Monterrey 64849, Mexico.

Microalgae are complex photosynthetic organisms found in marine and freshwater environments that produce valuable metabolites. Microalgae-derived metabolites have gained remarkable attention in different industrial biotechnological processes and pharmaceutical and cosmetic industries due to their multiple properties, including antioxidant, anti-aging, anti-cancer, phycoimmunomodulatory, anti-inflammatory, and antimicrobial activities. These properties are recognized as promising components for state-of-the-art cosmetics and cosmeceutical formulations. Efforts are being made to develop natural, non-toxic, and environmentally friendly products that replace synthetic products. This review summarizes some potential cosmeceutical applications of microalgae-derived biomolecules, their mechanisms of action, and extraction methods.
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http://dx.doi.org/10.3390/molecules27113512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9182589PMC
May 2022

Accelerated 3D myelin water imaging using joint spatio-temporal reconstruction.

Med Phys 2022 Jun 9. Epub 2022 Jun 9.

Department of Electrical and Electronic Engineering, Yonsei University, Seoul, Republic of Korea.

Purpose: To enable acceleration in 3D multi-echo gradient echo (mGRE) acquisition for myelin water imaging (MWI) by combining joint parallel imaging (JPI) and joint deep learning (JDL).

Methods: We implemented a multistep reconstruction process using both advanced parallel imaging and deep learning network which can utilize joint spatiotemporal components between the multi-echo images to further accelerate 3D mGRE acquisition for MWI. In the first step, JPI was performed to estimate missing k-space lines. Next, JDL was implemented to reduce residual artifacts and produce high-fidelity reconstruction by using variable splitting optimization consisting of spatiotemporal denoiser block, data consistency block, and weighted average block. The proposed method was evaluated for MWI with 2D Cartesian uniform under-sampling for each echo, enabling scan times of up to approximately 2 min for 3D coverage.

Results: The proposed method showed acceptable MWI quality with improved quantitative values compared to both JPI and JDL methods individually. The improved performance of the proposed method was demonstrated by the low normalized mean-square error and high-frequency error norm values of the reconstruction with high similarity to the fully sampled MWI.

Conclusion: Joint spatiotemporal reconstruction approach by combining JPI and JDL can achieve high acceleration factors for 3D mGRE-based MWI.
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http://dx.doi.org/10.1002/mp.15788DOI Listing
June 2022

Enterococcus faecium and Pediococcus acidilactici deteriorate Enterobacteriaceae-induced depression and colitis in mice.

Sci Rep 2022 06 7;12(1):9389. Epub 2022 Jun 7.

Neurobiota Research Center, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Korea.

Gut dysbiosis is closely associated with the outbreak of inflammatory bowel disease (IBD) and psychiatric disorder. The Enterobacteriaceae population was higher in the feces of patients with inflammatory bowel disease (IBD-F) than in those of healthy control volunteers (HC-F). The Enterococcaceae and Lactobacillaceae populations were higher in the feces of IBD patients with depression (IBD/D-F) vs. the feces of IBD patients without depression (IBD/D-F). Therefore, we examined the effects of Klebsiella oxytoca, Escherichia coli, Cronobacter sakazakii, Enterococcus faecium, and Pediococcus acidolactici overpopulated in IBD/D-F and their byproducts LPS and exopolysaccharide (EPS) on the occurrence of depression and colitis in mice. Oral gavages of Klebsiella oxytoca, Escherichia coli, and Cronobacter sakazakii belonging to Enterobacteriaceae, singly or together, caused dose-dependently colitis and depression-like behaviors in germ-free and specific-pathogen-free mice. Although Enterococcus faecium and Pediococcus acidolactici did not significantly cause colitis and depression-like behaviors, they significantly deteriorated Klebsiella oxytoca- or Escherichia coli-induced colitis, neuroinflammation, and anxiety/depression-like behaviors and increased blood LPS, corticosterone, and IL-6 levels. The EPSs from Enterococcus faecium and Pediococcus acidolactici also worsened Klebsiella oxytoca LPS-induced colitis, neuroinflammation, and depression-like behaviors in mice and increased the translocation of fluorescein isothiocyanate-conjugated LPS into the hippocampus. However, Bifidobacterium longum, which was lower in IBD/D-F vs. IBD/D-F, or its EPS suppressed them. In conclusion, Enterococcus faecium and Pediococcus acidolactici, known as a probiotic strain, and their EPSs may be a risk factor for the outbreak of depression and IBD.
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http://dx.doi.org/10.1038/s41598-022-13629-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174183PMC
June 2022

Natural aging course of lumbar extensor muscle mass and strength in community-dwelling older women: a 1-year prospective observational study.

Aging Clin Exp Res 2022 Jun 6. Epub 2022 Jun 6.

Department of Rehabilitation Medicine, Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul, 07061, Republic of Korea.

Background: Although the loss of skeletal limb muscle mass and muscle strength in the elderly have been demonstrated, the aging process of the back muscles to maintain core stability is not well known. This 1-year prospective observational study aimed to investigate the natural aging course of the lumbar extensor muscles (LEMs) compared with the extremity muscles and determine whether muscle strength or mass decreases more in community-dwelling older women.

Methods: Twenty-four older urban-dwelling women aged 70 years or older were initially enrolled. Their demographic variables, conventional and spinal sarcopenia indices, and functional outcome parameters were evaluated. We also measured back extensor strength, radiological parameters for spinal sagittal balance on whole-spine radiography, and volumetric parameters of the LEM on computed tomography.

Results: After the exclusion of 6 subjects, 18 older women were finally analyzed. All variables related to extremity muscle mass, muscle strength, physical performance, and LEM volume declined over the study period, but the changes were insignificant. However, back extensor strength decreased significantly (median, first, and third quartile: 35.20 [30.80, 44.00] N to 31.40 [29.25, 37.90] N, P = 0.026). Among spinal sagittal balance-related parameters, lumbar lordosis (44.25 [39.30, 47.35]° to 43.15 [31.43, 45.75]°, P = 0.043) and sagittal vertical axis (33.85 [3.57, 58.75] mm to 45.15 [25.35, 58.68] mm, P = 0.004) showed significant changes during the study.

Conclusions: When the natural aging course of LEM in women aged 70 years or older was observed for 1 year, muscle mass decreased less than back extensor strength and spinal sagittal balance. Measurements of back extensor strength and spinal sagittal balance are necessary for the clinical evaluation of spinal aging.
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http://dx.doi.org/10.1007/s40520-022-02156-2DOI Listing
June 2022

Multifunctional Nanocarriers-Mediated Synergistic Combination of Immune Checkpoint Inhibitor Cancer Immunotherapy and Interventional Oncology Therapy.

Adv Nanobiomed Res 2021 Oct 2;1(10). Epub 2021 Aug 2.

Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States.

Immune checkpoint inhibitor (ICI) cancer immunotherapies are becoming one of the standard therapies for cancer patients. However, ICI cancer immunotherapy's overall response rate is still moderate and even combinational ICI cancer immunotherapies are not showing significant improvement in therapeutic outcomes. Only a subset of patients responds to the therapy due to the resistance and ignorance to the ICI cancer immunotherapy. Following immune-related adverse events (irAEs) are also limiting the whole therapeutic regimens. New approaches that can increase the immunotherapeutic efficacy and reduce systemic irAEs are required. Recently, multifunctional nanocarriers, which can extend the half-life of ICIs and modulate tumor microenvironment (TME), have shown a substantial opportunity to enhance ICI cancer immunotherapies. Interventional oncology (IO) allowing simultaneous diagnosis, immunogenic loco-regional therapeutic delivery, and real-time monitoring of the treatment efficacy have advanced to demonstrate the effective conversion of TME. The use of multifunctional nanocarriers with the IO therapies amplify the image guidance capability and immunogenic therapeutic localization for the potential combinational ICI cancer immunotherapy. This article will discuss the emerging opportunity of multifunctional nanocarriers mediated synergistic combination of ICI cancer immunotherapy and IO local therapy.
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http://dx.doi.org/10.1002/anbr.202100010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9162439PMC
October 2021
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