Publications by authors named "Sang Soo Lee"

597 Publications

Betaine, a component of , enhances muscular endurance of mice and myogenesis of myoblasts.

Food Sci Nutr 2021 Sep 14;9(9):5083-5091. Epub 2021 Jul 14.

Department of Biochemistry Chungnam National University Daejeon Korea.

Sarcopenia is a disease characterized by the loss of muscle mass and function that occurs mainly in older adults. The present study was designed to investigate the hypothesis that water extract of (WELC) would improve muscle function and promote myogenesis for sarcopenia. We investigated the effect of water extracts of .  on muscular endurance function and myogenesis to examine its efficacy in sarcopenia. Intake of WELC-containing cheese enhanced the muscular endurance function of mice in treadmill endurance tests. In addition, the cross-sectional areas of muscle fibers in the gastrocnemius muscle of . -fed mice were greater than that of control mice. Furthermore, WELC and its key component marker substance betaine promoted myogenesis of myoblasts by increasing the expression of the myogenic protein myosin heavy chain 3 (Myh3) and myotube formation. Taken together, our results suggest that .  may potentially be useful in the development of preventive and therapeutic agents for sarcopenia, as well as in providing basic knowledge on myogenesis and muscular functions.
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http://dx.doi.org/10.1002/fsn3.2466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441376PMC
September 2021

Construction of biotreatment platforms for aromatic hydrocarbons and their future perspectives.

J Hazard Mater 2021 08 29;416:125968. Epub 2021 Apr 29.

Department of Chemical Engineering & Technology Indian Institute of Technology (BHU), Varanasi 221005, Uttar Pradesh, India.

Aromatic hydrocarbons (AHCs) are one of the major environmental pollutants introduced from both natural and anthropogenic sources. Many AHCs are well known for their toxic, carcinogenic, and mutagenic impact on human health and ecological systems. Biodegradation is an eco-friendly and cost-effective option as microorganisms (e.g., bacteria, fungi, and algae) can efficiently breakdown or transform such pollutants into less harmful and simple metabolites (e.g., carbon dioxide (aerobic), methane (anaerobic), water, and inorganic salts). This paper is organized to offer a state-of-the-art review on the biodegradation of AHCs (monocyclic aromatic hydrocarbons (MAHs) and polycyclic aromatic hydrocarbons (PAHs)) and associated mechanisms. The recent progress in biological treatment using suspended and attached growth bioreactors for the biodegradation of AHCs is also discussed. In addition, various substrate growth and inhibition models are introduced along with the key factors governing their biodegradation kinetics. The growth and inhibition models have helped gain a better understanding of substrate inhibition in biodegradation. Techno-economic analysis (TEA) and life cycle assessment (LCA) aspects are also described to assess the technical, economical, and environmental impacts of the biological treatment system.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125968DOI Listing
August 2021

D614G mutation eventuates in all VOI and VOC in SARS-CoV-2: Is it part of the positive selection pioneered by Darwin?

Mol Ther Nucleic Acids 2021 Dec 1;26:237-241. Epub 2021 Sep 1.

College of Pharmacy and Health Care, Tajen University, Yanpu, Pingtung 907, Taiwan.

Recently, several emerging variants of SARS-CoV-2 have originated from the Wuhan strain and spread throughout the globe within one and a half years. One mutation, D614G, is very prominent in all VOI and VOC in SARS-CoV-2. This mutation might help to increase the viral fitness in all emerging variants where the mutation is present. With the help of this mutation (D614G), the SARS-CoV-2 variants have gained viral fitness to enhance viral replication and increase transmission. This paper attempts to answer the question of whether the mutation (D614G) occurs due to positive selection or not.
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http://dx.doi.org/10.1016/j.omtn.2021.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408019PMC
December 2021

Recent research progress on circular RNAs: Biogenesis, properties, functions, and therapeutic potential.

Mol Ther Nucleic Acids 2021 Sep 4;25:355-371. Epub 2021 Jun 4.

Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Barasat-Barrackpore Road, Jagannathpur, Kolkata, West Bengal 700126, India.

Circular RNAs (circRNAs), an emerging family member of RNAs, have gained importance in research due to their new functional roles in cellular physiology and disease progression. circRNAs are usually available in a wide range of cells and have shown tissue-specific expression as well as developmental specific expression. circRNAs are characterized by structural stability, conservation, and high abundance in the cell. In this review, we discuss the different models of biogenesis. The properties of circRNAs such as localization, structure and conserved pattern, stability, and expression specificity are also been illustrated. Furthermore, we discuss the biological functions of circRNAs such as microRNA (miRNA) sponging, cell cycle regulation, cell-to-cell communication, transcription regulation, translational regulation, disease diagnosis, and therapeutic potential. Finally, we discuss the recent research progress and future perspective of circRNAs. This review provides an understanding of potential diagnostic markers and the therapeutic potential of circRNAs, which are emerging daily.
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http://dx.doi.org/10.1016/j.omtn.2021.05.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399087PMC
September 2021

Evolution, Mode of Transmission, and Mutational Landscape of Newly Emerging SARS-CoV-2 Variants.

mBio 2021 08 31;12(4):e0114021. Epub 2021 Aug 31.

Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si, Gangwon-do, Republic of Korea.

The recent emergence of multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a significant concern for public health worldwide. New variants have been classified either as variants of concern (VOCs) or variants of interest (VOIs) by the CDC (USA) and WHO. The VOCs include lineages such as B.1.1.7 (20I/501Y.V1 variant), P.1 (20J/501Y.V3 variant), B.1.351 (20H/501Y.V2 variant), and B.1.617.2. In contrast, the VOI category includes B.1.525, B.1.526, P.2, and B.1.427/B.1.429. The WHO provided the alert for last two variants (P.2 and B.1.427/B.1.429) and labeled them for further monitoring. As per the WHO, these variants can be reclassified due to their status at a particular time. At the same time, the CDC (USA) has marked these two variants as VOIs up through today. This article analyzes the evolutionary patterns of all these emerging variants, as well as their geographical distributions and transmission patterns, including the circulating frequency, entropy diversity, and mutational event diversity throughout the genomes of all SARS-CoV-2 lineages. The transmission pattern was observed highest in the B.1.1.7 lineage. Our frequency evaluation found that this lineage achieved 100% frequency in early October 2020. We also critically evaluated the above emerging variants mutational landscape and significant spike protein mutations (E484K, K417T/N, N501Y, and D614G) impacting public health. Finally, the effectiveness of vaccines against newly SARS-CoV-2 variants was also analyzed. Irrespective of the aggressive vaccination drive, the newly emerging multiple SARS-CoV-2 variants are causing havoc in several countries. As per the CDC (USA) and WHO, the VOCs include the B.1.1.7, P.1, B.1.351, and B.1.617.2 lineages, while the VOIs include the B.1.525, B.1.526, P.2, and B.1.427/B.1.429 lineages. This study analyzed the evolutionary patterns, geographical distributions and transmission patterns, circulating frequency, entropy diversity, and mutational event diversity throughout the genome of significant SARS-CoV-2 lineages. A higher transmission pattern was observed for the B.1.1.7 variant. The study also evaluated the mutational landscape and important spike protein mutations (E484K, K417T/N, N501Y, and D614G) of all of the above variants. Finally, a survey was performed on the efficacy of vaccines against these variants from the previously published literature. The results presented in this article will help design future countrywide pandemic planning strategies for the emerging variants, next-generation vaccine development using alternative wild-type antigens and significant viral antigens, and immediate planning for ongoing vaccination programs worldwide.
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http://dx.doi.org/10.1128/mBio.01140-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406297PMC
August 2021

Pancreatic/peripancreatic neurogenic tumor; little known masses not to be missed.

Pancreatology 2021 Aug 18. Epub 2021 Aug 18.

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Background: Retroperitoneal neurogenic tumors are extremely rare pathological entities; therefore, few clinical features and natural courses, especially originating from the pancreatic/peripancreatic regions, have been reported. This study aimed to investigate the clinicopathological features of pancreatic and peripancreatic neurogenic tumors and assess the diagnostic value of computed tomography (CT) and endoscopic ultrasound-guided fine needle biopsy (EUS-FNB).

Methods: Between 2006 and 2018, patients who were diagnosed with neurogenic tumors were included. In total, 90 histologically confirmed cases of neurogenic tumors located in the pancreatic/peripancreatic regions were selected for analysis.

Results: The mean age was 49.2 ± 13.1 years. There were no differences in sex distribution of the tumors. Schwannomas (44.4%) and paragangliomas (41.1%) were the most common neurogenic tumors. The sensitivity of CT was 62.2% in 90 cases. EUS-FNB was performed in 30 cases and the sensitivity of it was 83.3%. The diagnosis of neurogenic tumors with EUS-FNB or CT was not significantly associated with tumor location and size. Surgical resection was performed in 78 cases. Of the 12 patients who did not undergo surgery, 10 cases were followed-up without any increase in tumor size.

Conclusions: Through the present study, we verified radiological, pathological, and clinical aspects of the pancreatic/peripancreatic neurogenic tumors which little known before, therefore, this study can serve as the basis for research to present an optimal diagnosis and treatment of neurogenic tumors. In addition, EUS-FNB is useful in the diagnosis of pancreatic/peripancreatic neurogenic tumors with relatively high sensitivity and can help establish therapeutic plans before the surgery.
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http://dx.doi.org/10.1016/j.pan.2021.08.005DOI Listing
August 2021

Serum Peptide Immunoglobulin G Autoantibody Response in Patients with Different Central Nervous System Inflammatory Demyelinating Disorders.

Diagnostics (Basel) 2021 Jul 26;11(8). Epub 2021 Jul 26.

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

Previous efforts to discover new surrogate markers for the central nervous system (CNS) inflammatory demyelinating disorders have shown inconsistent results; moreover, supporting evidence is scarce. The present study investigated the IgG autoantibody responses to various viral and autoantibodies-related peptides proposed to be related to CNS inflammatory demyelinating disorders using the peptide microarray method. We customized a peptide microarray containing more than 2440 immobilized peptides representing human and viral autoantigens. Using this, we tested the sera of patients with neuromyelitis optica spectrum disorders (NMOSD seropositive, = 6; NMOSD seronegative, = 5), multiple sclerosis (MS, = 5), and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD, = 6), as well as healthy controls (HC, = 5) and compared various peptide immunoglobulin G (IgG) responses between the groups. Among the statistically significant peptides based on the pairwise comparisons of IgG responses in each disease group to HC, cytomegalovirus (CMV)-related peptides were most clearly distinguishable among the study groups. In particular, the most significant differences in IgG response were observed for HC vs. MS and HC vs. seronegative NMOSD ( = 0.064). Relatively higher IgG responses to CMV-related peptides were observed in patients with MS and NMOSD based on analysis of the customized peptide microarray.
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http://dx.doi.org/10.3390/diagnostics11081339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392162PMC
July 2021

Polydeoxyribonucleotide and Polynucleotide Improve Tendon Healing and Decrease Fatty Degeneration in a Rat Cuff Repair Model.

Tissue Eng Regen Med 2021 Aug 13. Epub 2021 Aug 13.

Department of Orthopedic Surgery, Chuncheon Sacred Heart Hospital, Hallym University Medical College, 77, Sakju-ro, Chuncheon-si, Gangwon-do, 24253, Republic of Korea.

Background: After surgical repair of chronic rotator cuff tears, healing of the repaired tendons often fails and is accompanied by high-level fatty degeneration. Our purpose was to explore the effects of polydeoxyribonucleotide (PDRN) and polynucleotide (PN) on tendon healing and the reversal of fatty degeneration in a chronic rotator cuff tear model using a rat infraspinatus.

Methods: Sixty rats were randomly assigned to the following three groups (20 rats per group: 12 for histological evaluation and 8 for mechanical testing): saline + repair (SR), PDRN + repair (PR), and PN + repair (PNR). The right shoulder was used for experimental intervention, and the left served as a control. Four weeks after detaching the infraspinatus, the torn tendon was repaired. Saline, PDRN, and PN were applied to the repair sites. Histological evaluation was performed 3 and 6 weeks after repair and biomechanical analysis was performed at 6 weeks.

Results: Three weeks after repair, the PR and PNR groups had more CD168-stained cells than the SR group. The PR group showed a larger cross-sectional area (CSA) of muscle fibers than the SR and PNR groups. Six weeks after repair, the PR and PNR groups showed more adipose cells, less CD68-stained cells, and more parallel tendon collagen fibers than the SR group. The PR group had more CD 68-stained cells than the PNR group. The PR group showed a larger CSA than the SR group. The mean load-to-failure values of the PR and PNR groups were higher than that of the SR group, although these differences were not significant.

Conclusion: PDRN and PN may improve tendon healing and decrease fatty degeneration after cuff repair.
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http://dx.doi.org/10.1007/s13770-021-00378-5DOI Listing
August 2021

Expression of HER2 and Mismatch Repair Proteins in Surgically Resected Gallbladder Adenocarcinoma.

Front Oncol 2021 22;11:658564. Epub 2021 Jul 22.

Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Background: Gallbladder cancer (GBC) has a poor prognosis. Although complete surgical resection is the only successful approach for improving survival, additional therapeutic modalities are required for recurrent or surgically unresectable GBCs.

Materials And Methods: To determine the expression status of HER2 and the mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2, immunohistochemical staining of MMR proteins and HER2 was carried out in 216 surgically resected GBCs. HER2 labeling was scored by adopting a scoring system for gastric carcinomas. Tissues scoring 0 to 2+ were defined as HER2 negative, whereas those scoring 3+ were regarded as HER2-positive. In addition, silver hybridization and microsatellite instability (MSI) analysis were conducted to confirm amplification and MSI, respectively.

Results: Three of 216 GBCs (1.3%) showed MMR protein deficiency. All three observed MSI cases exhibited dual loss of MSH2 and MSH6 protein expression. However, no cases showed loss of either MLH1 or PMS2 expression. No association was observed between MMR protein deficiency and other clinicopathological factors. amplification was noted in 30 (13.9%) GBCs and associated with Crohn-like lymphoid reaction (P = 0.023). No survival difference was observed based on HER2 overexpression or amplification status.

Conclusion: MMR protein deficiency and HER2 overexpression were observed in a small subset (1.3% and 13.9%, respectively) of GBCs without simultaneous occurrence of deficient MMR protein expression and HER2 overexpression. The presence of Crohn-like lymphoid reaction may help identify cases with amplification, by using hematoxylin-stained slides. Although the proportion of MMR protein-deficient- and HER2-overexpressing GBCs was small, applying immunotherapy to MMR protein-deficient GBCs and herceptin to HER2-overexpressing GBCs may provide alternative treatment options for patients with GBC.
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http://dx.doi.org/10.3389/fonc.2021.658564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339709PMC
July 2021

Ion correlations drive charge overscreening and heterogeneous nucleation at solid-aqueous electrolyte interfaces.

Proc Natl Acad Sci U S A 2021 Aug;118(32)

Chemical Sciences and Engineering Division, Argonne National Laboratory, Lemont, IL 60439.

Classical electrical double layer (EDL) models are foundational to the representation of atomistic structure and reactivity at charged interfaces. An important limitation to these models is their dependence on a mean-field approximation that is strictly valid for dilute aqueous solutions. Theoretical efforts to overcome this limitation are severely impeded by the lack of visualization of the structure over a wide range of ion concentration. Here, we report the salinity-dependent evolution of EDL structure at negatively charged mica-water interfaces, revealing transition from the Langmuir-type charge compensation in dilute salt solutions to nonclassical charge overscreening in highly concentrated solutions. The EDL structure in this overcharging regime is characterized by the development of both lateral positional correlation between adsorbed ions and vertical layering of alternating cations and anions reminiscent of the structures of strongly correlated ionic liquids. These EDL ions can spontaneously grow into nanocrystalline nuclei of ionic compounds at threshold ion concentrations that are significantly lower than the bulk solubility limit. These results shed light on the impact of ion cooperativity that drives heterogeneous nonclassical behaviors of the EDL in high-salinity conditions.
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http://dx.doi.org/10.1073/pnas.2105154118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364158PMC
August 2021

Recent developments and strategies of Ebola virus vaccines.

Curr Opin Pharmacol 2021 Jul 27;60:46-53. Epub 2021 Jul 27.

Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si, 24252, Gangwon-do, Republic of Korea. Electronic address:

The Filovirus family member, Ebola virus (EBOV), is a highly infectious pathogen responsible for viral hemorrhagic fever. EBOV has a fatality rate in the range 50%-90% in primates. The lethal viral hemorrhagic attack in 2014 by EBOV has forced the human race to look for rapid countermeasures. Fortunately, owing to continuous efforts and several vaccine platforms, few potential vaccine candidates are emerging, such as replicative and non-replicative vectored vaccines, polyepitopic or monovalent vaccines, and DNA vaccines. This article reviewed various kinds of EBOV vaccines in different clinical trial phases and their approval status. Updated knowledge of vaccine development progress might stimulate the researchers to look for more potent and effective vaccine candidates against EBOV.
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http://dx.doi.org/10.1016/j.coph.2021.06.008DOI Listing
July 2021

From COVID-19 to Cancer mRNA Vaccines: Moving From Bench to Clinic in the Vaccine Landscape.

Front Immunol 2021 7;12:679344. Epub 2021 Jul 7.

Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, Gangwon-do, South Korea.

Recently, mRNA vaccines have become a significant type of therapeutic and have created new fields in the biopharmaceutical industry. mRNA vaccines are promising next-generation vaccines that have introduced a new age in vaccinology. The recent approval of two COVID-19 mRNA vaccines (mRNA-1273 and BNT162b2) has accelerated mRNA vaccine technology and boosted the pharmaceutical and biotechnology industry. These mRNA vaccines will help to tackle COVID-19 pandemic through immunization, offering considerable hope for future mRNA vaccines. Human trials with data both from mRNA cancer vaccines and mRNA infectious disease vaccines have provided encouraging results, inspiring the pharmaceutical and biotechnology industries to focus on this area of research. In this article, we discuss current mRNA vaccines broadly in two parts. In the first part, mRNA vaccines in general and COVID-19 mRNA vaccines are discussed. We presented the mRNA vaccine structure in general, the different delivery systems, the immune response, and the recent clinical trials for mRNA vaccines (both for cancer mRNA vaccines and different infectious diseases mRNA vaccines). In the second part, different COVID-19 mRNA vaccines are explained. Finally, we illustrated a snapshot of the different leading mRNA vaccine developers, challenges, and future prospects of mRNA vaccines.
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http://dx.doi.org/10.3389/fimmu.2021.679344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293291PMC
August 2021

Bioremediation strategies with biochar for polychlorinated biphenyls (PCBs)-contaminated soils: A review.

Environ Res 2021 09 23;200:111757. Epub 2021 Jul 23.

School of Environmental Engineering, University of Seoul, Seoul, 02504, Republic of Korea. Electronic address:

Polychlorinated biphenyls (PCBs) are hazardous organic contaminants threatening human health and environmental safety due to their toxicity and carcinogenicity. Biochar (BC) is an eco-friendly carbonaceous material that can extensively be utilized for the remediation of PCBs-contaminated soils. In the last decade, many studies reported that BC is beneficial for soil quality enhancement and agricultural productivity based on its physicochemical characteristics. In this review, the potential of BC application in PCBs-contaminated soils is elaborated as biological strategies (e.g., bioremediation and phytoremediation) and specific mechanisms are also comprehensively demonstrated. Further, the synergy effects of BC application on PCBs-contaminated soils are discussed, in view of eco-friendly, beneficial, and productive aspects.
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http://dx.doi.org/10.1016/j.envres.2021.111757DOI Listing
September 2021

Lessons Learned from Cutting-Edge Immunoinformatics on Next-Generation COVID-19 Vaccine Research.

Int J Pept Res Ther 2021 Jul 10:1-9. Epub 2021 Jul 10.

Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si, 24252 Gangwon-do Republic of Korea.

Presently, immunoinformatics and bioinformatics approaches are contributing actively to COVID-19 vaccine research. The first immunoinformatics-based vaccine construct against SARS-CoV-2 was published in February 2020. Following this, immunoinformatics and bioinformatics approaches have created a new direction in COVID-19 vaccine research. Several researchers have designed the next-generation COVID-19 vaccines using these approaches. Presently, immunoinformatics has accelerated immunology research immensely in the area of COVID-19. Hence, we have tried to depict the current scenario of immunoinformatics and bioinformatics in COVID-19 vaccine research.

Supplementary Information: The online version contains supplementary material available at 10.1007/s10989-021-10254-4.
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http://dx.doi.org/10.1007/s10989-021-10254-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272614PMC
July 2021

Current status of endoscopic management of cholecystitis.

Dig Endosc 2021 Jul 18. Epub 2021 Jul 18.

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

Laparoscopic cholecystectomy remains the standard treatment for acute cholecystitis (AC) although it is always not suitable for patients who are poor candidates for surgery. Recently, endoscopic gallbladder (GB) drainage was found to be a potentially revolutionary alternative for cholecystectomy for the control of symptoms, definitive treatment, or bridging therapy until surgery is possible. Two endoscopic methods have been established using either the trans-mural or trans-papillary drainage approach. Endoscopic ultrasound-guided GB drainage (EUS-GBD; trans-mural approach) is a novel technique that allows stent placement between the GB and duodenum or stomach via fistula track, effectively enabling GB drainage. For endoscopic trans-papillary GB drainage (ETGBD; trans-papillary approach), attempts of selective cannulation to the cystic duct should be made to place the stent in the same manner as an endoscopic retrograde cholangiopancreatography. In comparison, EUS-GBD has higher clinical success and lower recurrence rates than ETGBD due to the use of larger-caliber stents, which allow for effective drainage when performed by skilled practitioners at high-volume centers. Advantages of ETGBD over EUS-GBD include more affordable costs and physiologic drainage, which preserves naive anatomy for possible future cholecystectomy. Although the field of endoscopic treatment for AC is rapidly advancing, important questions regarding which method improves clinical outcomes and safety more effectively remain unaddressed. Herein, the current status of endoscopic treatment for AC, including a technical review on clinical outcomes, adverse events, and advantages and disadvantages of each technique are reviewed, as well as other future prospects.
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http://dx.doi.org/10.1111/den.14083DOI Listing
July 2021

Impact of acute kidney injury on mortality in patients with acute variceal bleeding.

BMC Gastroenterol 2021 Jul 13;21(1):290. Epub 2021 Jul 13.

Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea.

Background: The effect of acute kidney injury (AKI) on patients with acute variceal bleeding (AVB) using the recently proposed International Club of Ascites (ICA) criteria is unclear. This study aimed to evaluate the incidence of AKI using the ICA criteria and factors associated with the outcomes in cirrhotic patients with AVB.

Methods: This retrospective cohort study included data of cirrhotic patients with AVB from two centers in Korea. The association of the ICA criteria for AKI with 6-week mortality was analyzed through univariate and multivariate analyses using the Cox proportional hazard model.

Results: In total, there were 546 episodes of AVB in 390 patients, of which 425 and 121 episodes were due to esophageal and gastric variceal bleeding, respectively. Moreover, 153 patients fulfilled the ICA criteria for AKI, and 64, 30, 39, and 20 patients were diagnosed with stages 1a, 1b, 2, and 3, respectively. Conversely, 97 patients developed AKI within 42 days as per the conventional criteria. The 6-week mortality rate was significantly higher in patients with ICA-AKI than in patients without ICA-AKI; the occurrence of ICA-AKI was an independent factor for predicting the 6-week mortality.

Conclusion: The ICA criteria could help diagnose renal dysfunction earlier, and presence of AKI is a predictor of mortality in patients with cirrhosis and AVB.
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http://dx.doi.org/10.1186/s12876-021-01862-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276463PMC
July 2021

Impact of non-hepatic hyperammonemia on mortality in intensive care unit patients: a retrospective cohort study.

Korean J Intern Med 2021 Jul 15. Epub 2021 Jul 15.

Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea.

Background/aims: The effect of hyperammonemia on the mortality in patients with liver cirrhosis is well documented. However, little is known about the impact of hyperammonemia on mortality among intensive care unit patients without hepatic disease. We aimed to investigate factors associated with non-hepatic hyperammonemia among intensive care unit patients and to evaluate the factors related to the 7- and 90-day mortality.

Methods: Between February 2016 and February 2020, 948 patients without hepatic disease who had 972 episodes of admission to the intensive care unit were retrospectively enrolled and classified as hyperammonemia grades 0 (≤ 80 µg/dL; 585 [60.2%]), 1 (≤ 160 µg/dL; 291 [29.9%]), 2 (≤ 240 µg/dL; 55 [5.7%]), and 3 (> 240 µg/dL; 41 [4.2%]). Factors associated with hyperammonemia and the 7- and 90-day mortality were evaluated by multivariate logistic regression analysis and Cox regression analysis, respectively. Kaplan-Meier survival curves for the 7- and 90-day mortality were constructed.

Results: The independent risk factors for hyperammonemia were male sex (odds ratio, 1.517), age (0.984/year), acute brain failure (2.467), acute kidney injury (1.437), prothrombin time-international normalized ratio (2.272/unit), and albumin (0.694/g/dL). The 90-day mortality rate in the entire cohort was 24.3% and gradually increased with increasing hyperammonemia grade at admission (17.9%, 28.2%, 43.6%, and 61.0% in patients with grades 0, 1, 2, and 3, respectively). Additionally, non-hepatic hyperammonemia was an independent predictor of the 90- day mortality in intensive care unit patients.

Conclusions: Non-hepatic hyperammonemia is common (39.8%) and associated with the 90-day mortality among intensive care unit patients.
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http://dx.doi.org/10.3904/kjim.2021.021DOI Listing
July 2021

The impact of preoperative EUS-FNA for distal resectable pancreatic cancer: Is it really effective enough to take risks?

Surg Endosc 2021 Jul 12. Epub 2021 Jul 12.

Division of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.

Background And Aims: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is frequently used for the preoperative histologic diagnosis of pancreatic cancer. However, debate continues regarding the clinical merits of preoperative EUS-FNA for the management of resectable pancreatic cancer. We aimed to evaluate the benefits and safety of preoperative EUS-FNA for resectable distal pancreatic cancer.

Methods: The medical records of 304 consecutive patients with suspected distal pancreatic cancer who underwent EUS-FNA were retrospectively reviewed to evaluate the clinical benefits of preoperative EUS-FNA. We also reviewed the medical records of 528 patients diagnosed with distal pancreatic cancer who underwent distal pancreatectomy with or without EUS-FNA. The recurrence rates and cancer-free survival periods of patients who did or did not undergo preoperative EUS-FNA were compared.

Results: The diagnostic accuracy of preoperative EUS-FNA was high (sensitivity, 87.5%; specificity, 100%; positive predictive value 100%; accuracy, 90.7%; negative predictive value, 73.8%). Among patients, 26.7% (79/304) avoided surgery based on the preoperative EUS-FNA findings. Of the 528 patients who underwent distal pancreatectomy, 193 patients received EUS-FNA and 335 did not. During follow-up (median 21.7 months), the recurrence rate was similar in the two groups (EUS-FNA, 72.7%; non-EUS-FNA, 75%; P = 0.58). The median cancer-free survival was also similar (P = 0.58); however, gastric wall recurrence was only encountered in the patients with EUS-FNA (n = 2).

Conclusion: Preoperative EUS-FNA is not associated with increased risks of cancer-specific or overall survival. However, clinicians must consider the potential risks of needle tract seeding, and care should be taken when selecting patients.
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http://dx.doi.org/10.1007/s00464-021-08627-3DOI Listing
July 2021

Sclerostin-Mediated Impaired Osteogenesis by Fibroblast-Like Synoviocytes in the Particle-Induced Osteolysis Model.

Front Mol Biosci 2021 23;8:666295. Epub 2021 Jun 23.

Institute for Skeletal Aging and Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon, South Korea.

Engineered biomaterials are envisioned to replace, augment, or interact with living tissues for improving the functional deformities associated with end-stage joint pathologies. Unfortunately, wear debris from implant interfaces is the major factor leading to periprosthetic osteolysis. Fibroblast-like synoviocytes (FLSs) populate the intimal lining of the synovium and are in direct contact with wear debris. This study aimed to elucidate the effect of Ti particles as wear debris on human FLSs and the mechanism by which they might participate in the bone remodeling process during periprosthetic osteolysis. FLSs were isolated from synovial tissue from patients, and the condition medium (CM) was collected after treating FLSs with sterilized Ti particles. The effect of CM was analyzed for the induction of osteoclastogenesis or any effect on osteogenesis and signaling pathways. The results demonstrated that Ti particles could induce activation of the NFκB signaling pathway and induction of COX-2 and inflammatory cytokines in FLSs. The amount of Rankl in the conditioned medium collected from Ti particle-stimulated FLSs (Ti CM) showed the ability to stimulate osteoclast formation. The Ti CM also suppressed the osteogenic initial and terminal differentiation markers for osteoprogenitors, such as alkaline phosphate activity, matrix mineralization, collagen synthesis, and expression levels of Osterix, Runx2, collagen 1α, and bone sialoprotein. Inhibition of the WNT and BMP signaling pathways was observed in osteoprogenitors after the treatment with the Ti CM. In the presence of the Ti CM, exogenous stimulation by WNT and BMP signaling pathways failed to stimulate osteogenic activity in osteoprogenitors. Induced expression of sclerostin (SOST: an antagonist of WNT and BMP signaling) in Ti particle-treated FLSs and secretion of SOST in the Ti CM were detected. Neutralization of SOST in the Ti CM partially restored the suppressed WNT and BMP signaling activity as well as the osteogenic activity in osteoprogenitors. Our results reveal that wear debris-stimulated FLSs might affect bone loss by not only stimulating osteoclastogenesis but also suppressing the bone-forming ability of osteoprogenitors. In the clinical setting, targeting FLSs for the secretion of antagonists like SOST might be a novel therapeutic approach for preventing bone loss during inflammatory osteolysis.
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http://dx.doi.org/10.3389/fmolb.2021.666295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260695PMC
June 2021

Association of mortality with drug-coated devices in femoropopliteal artery based on the nationwide data.

Ann Surg Treat Res 2021 Jul 30;101(1):20-27. Epub 2021 Jun 30.

Department of Physiology, Chung-Ang University School of Medicine, Seoul, Korea.

Purpose: Drug-coated devices have been widely accepted as one of the most promising therapies for femoropopliteal artery revascularization. A recent meta-analysis showed increased mortality in patients treated with drug-coated devices. We sought to examine the association between mortality and drug-coated devices after the treatment of the femoropopliteal artery based on the Korea national administrative claims data.

Methods: In the National Health Insurance Service database from August 2015 to December 2017, we identified patients with femoropopliteal artery revascularization using percutaneous transluminal angioplasty (PTA), bare metal stents (BMS), drug-coated balloon (DCB), or drug-eluting stents (DES). Kaplan-Meier methods were used to estimate the survival among devices, and log-rank tests were used to evaluate differences between groups. Adjusted hazard ratios (aHRs) were computed using the inverse probability of treatment weightings (IPTW).

Results: There were 1,724 patients (mean age, 70.9 ± period was 552 days (interquartile range, 404-688 days). There was a difference in IPTW-adjusted mortality risk among device types (26.3% in PTA, 22.1% in BMS, 17.7% in DCB, and 17.8% in DES; P = 0.004). IPTW-adjusted Cox nproportional hazard analysis showed that drug-coated devices were associated with decreased all-cause mortality risk (aHR, 0.70; 95% confidence interval, 0.58-0.86).

Conclusion: Our real-world analysis showed that there was no evidence of increased all-cause mortality after femoropopliteal artery revascularization with drug-coated devices compared with non-drug-coated devices.
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http://dx.doi.org/10.4174/astr.2021.101.1.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255583PMC
July 2021

Determination of k-mer density in a DNA sequence and subsequent cluster formation algorithm based on the application of electronic filter.

Sci Rep 2021 Jul 1;11(1):13701. Epub 2021 Jul 1.

Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Barasat-Barrackpore, Rd, Jagannathpur, Kolkata, West Bengal, 700126, India.

We describe a novel algorithm for information recovery from DNA sequences by using a digital filter. This work proposes a three-part algorithm to decide the k-mer or q-gram word density. Employing a finite impulse response digital filter, one can calculate the sequence's k-mer or q-gram word density. Further principal component analysis is used on word density distribution to analyze the dissimilarity between sequences. A dissimilarity matrix is thus formed and shows the appearance of cluster formation. This cluster formation is constructed based on the alignment-free sequence method. Furthermore, the clusters are used to build phylogenetic relations. The cluster algorithm is in good agreement with alignment-based algorithms. The present algorithm is simple and requires less time for computation than other currently available algorithms. We tested the algorithm using beta hemoglobin coding sequences (HBB) of 10 different species and 18 primate mitochondria genome (mtDNA) sequences.
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http://dx.doi.org/10.1038/s41598-021-93154-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249421PMC
July 2021

Asian-Origin Approved COVID-19 Vaccines and Current Status of COVID-19 Vaccination Program in Asia: A Critical Analysis.

Vaccines (Basel) 2021 Jun 4;9(6). Epub 2021 Jun 4.

Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si 24252, Gangwon-do, Korea.

COVID-19 vaccination has started throughout the globe. The vaccination program has also begun in most Asian countries. This paper analyzed the Asian-origin COVID-19 vaccines and vaccination program status in Asia till March 2021 under three sections. In the first section, we mapped the approved vaccines that originated from Asia, their technological platforms, collaborations during vaccine development, and regulatory approval from other countries. We found that a total of eight Asian COVID-19 vaccines originated and got approval from three countries: China, India, and Russia. In the second section, we critically evaluated the recent progress of COVID-19 vaccination programs. We analyzed the overall vaccination status across the Asian region. We also calculated the cumulative COVID-19 vaccine doses administered in different Asian countries, vaccine rolling in 7-day average in various Asian countries, and COVID-19 vaccine per day doses administrated in several Asian countries. We found that China and India vaccinated the maximum number of people. Finally, we evaluated the factors affecting the COVID-19 vaccination program in Asia, such as vaccine hesitancy, basic reproduction numbers (R0) and vaccination campaigns, and the cost of the vaccines. Our analysis will assist the implementation of the COVID-19 vaccination program successfully in Asia.
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http://dx.doi.org/10.3390/vaccines9060600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226479PMC
June 2021

Comparison of two digital PCR methods for EGFR DNA and SARS-CoV-2 RNA quantification.

Clin Chim Acta 2021 Oct 16;521:9-18. Epub 2021 Jun 16.

Biomolecular Measurement Team, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea. Electronic address:

Background: The COVID-19 pandemic caused by the severe acute SARS-CoV-2 virus has undeniably highlighted the importance of reliable nucleic acid quantification. Digital PCR (dPCR) is capable of the absolute quantification of nucleic acids.

Method: By using the droplet dPCR (QX200) and the digital real-time PCR (LOAA), the copy numbers were compared via multiple assays for three distinct targerts; EGFR DNA, SARS-CoV-2 and HIV-1 RNA.

Results: The droplet dPCR and digital real-time PCR showed similar copy numbers for both DNA and RNA quantification. When the limit of detection (LOD) and limit of quantitation (LOQ) of each method were estimated for DNA and RNA targets, the digital real-time PCR showed a higher sensitivity and precision especially with low copy number targets.

Conclusion: The breath of nucleic acid testing in diagnostic applications continues to expand. In this study we applied common diagnostic targets to a novel digital real-time PCR methodology. It performed comparably to the established dPCR method with distinctive advantages and disadvantages for implementing in laboratories. These rapidly developing dPCR systems can be applied to benefit the accurate and sensitive nucleic acid testing for various clinical areas.
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http://dx.doi.org/10.1016/j.cca.2021.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206622PMC
October 2021

SARS-CoV-2 Brazil variants in Latin America: More serious research urgently needed on public health and vaccine protection.

Ann Med Surg (Lond) 2021 Jun 5;66:102428. Epub 2021 Jun 5.

College of Pharmacy and Health Care, Tajen University, Yanpu, Pingtung, Taiwan.

COVID-19 has not only created a pandemic but also affected both economically and socially in all countries. It has further created a socio-economic chaos throughout Latin America. Currently, some new SARS-CoV-2 variants are circulating in Latin America and one among the significant variant belongs to the P.1 lineage (B.1.1.28.1) that has 17 mutations. The essential modifications located in the spike glycoprotein RBD include E484K, K417T and N501Y. Along with the P.1 lineage, P.2 lineage (B.1.1.28.2) has also appeared recently. Details on all the variants are unknown, along with the Brazil variants at this time. Therefore, we call for intensive research to collect more data to understand the variants' virulence and the effects on vaccine efficacy.
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http://dx.doi.org/10.1016/j.amsu.2021.102428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178066PMC
June 2021

All Nations Must Prioritize the COVID-19 Vaccination Program for Elderly Adults Urgently.

Aging Dis 2021 Jun 1;12(3):688-690. Epub 2021 Jun 1.

2Department of Zoology, Fakir Mohan University, VyasaVihar, Balasore 756020, Odisha, India.

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http://dx.doi.org/10.14336/AD.2021.0426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139210PMC
June 2021

Designing an effective therapeutic siRNA to silence RdRp gene of SARS-CoV-2.

Infect Genet Evol 2021 09 2;93:104951. Epub 2021 Jun 2.

Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Barasat-Barrackpore Rd, Jagannathpur, Kolkata, West Bengal 700126, India. Electronic address:

The devastating outbreak of COVID-19 has spread all over the world and has become a global health concern. There is no specific therapeutics to encounter the COVID-19. Small interfering RNA (siRNA)-based therapy is an efficient strategy to control human viral infections employing post-transcriptional gene silencing (PTGS) through neutralizing target complementary mRNA. RNA-dependent RNA polymerase (RdRp) encoded by the viral RdRp gene as a part of the replication-transcription complex can be adopted as an acceptable target for controlling SARS-CoV-2 mediated infection. Therefore, in the current study, accessible siRNA designing tools, including significant algorithms and parameters, were rationally used to design the candidate siRNAs against SARS-COV-2 encoded RdRp. The designed siRNA molecules possessed adequate nucleotide-based and other features for potent gene silencing. The targets of the designed siRNAs revealed no significant matches within the whole human genome, ruling out any possibilities for off-target silencing by the siRNAs. Characterization with different potential parameters of efficacy allowed selecting the finest siRNA among all the designed siRNA molecules. Further, validation assessment and target site accessibility prediction also rationalized the suitability of this siRNA molecule. Molecular docking study between the selected siRNA molecule and component of RNA interference (RNAi) pathway gave an excellent outcome. Molecular dynamics of two complexes: siRNA and argonaute complex, guide RNA, and target protein complex, have shown structural stability of these proteins. Therefore, the designed siRNA molecule might act as an effective therapeutic agent against the SARS-CoV-2 at the genome level and can prevent further outbreaks of COVID-19 in humans.
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http://dx.doi.org/10.1016/j.meegid.2021.104951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170914PMC
September 2021

Synthesis of Sulfonated Poly(Arylene Ether Sulfone)s Containing Aliphatic Moieties for Effective Membrane Electrode Assembly Fabrication by Low-Temperature Decal Transfer Methods.

Polymers (Basel) 2021 May 24;13(11). Epub 2021 May 24.

Center for Hydrogen and Fuel Cell Research, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.

The purpose of this study was to investigate the effect of the aliphatic moiety in the sulfonated poly(arylene ether sulfone) (SPAES) backbone. A new monomer (4,4'-dihydroxy-1,6-diphenoxyhexane) was synthesized and polymerized with other monomers to obtain partially alkylated SPAESs. According to differential scanning calorimetry analysis, the glass transition temperature (T) of these polymers ranged from 85 to 90 °C, which is 100 °C lower than that of the fully aromatic SPAES. Due to the low T values obtained for the partially alkylated SPAESs, it was possible to prepare a hydrocarbon electrolyte membrane-based membrane electrode assembly (MEA) with Nafion binder in the electrode through the use of a decal transfer method, which is the most commercially suitable system to obtain an MEA of proton exchange membrane fuel cells (PEMFCs). A single cell prepared using this partially alkylated SPAES as an electrolyte membrane exhibited a peak power density of 539 mW cm.
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http://dx.doi.org/10.3390/polym13111713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197277PMC
May 2021

Real-world Effectiveness and Safety of Direct-acting Antiviral Agents in Patients with Chronic Hepatitis C Genotype 2 Infection: Korean Multicenter Study.

J Korean Med Sci 2021 May 31;36(21):e142. Epub 2021 May 31.

Department of Internal Medicine, Ulsan University College of Medicine, Ulsan, Korea.

Background: The advancement of treatment with direct-acting antiviral (DAA) agents has improved the cure rate of hepatitis C virus (HCV) infection close to 100%. The aim of our study was to assess the real-world effectiveness and safety of DAA regimens for the treatment of patients with chronic HCV genotype 2.

Methods: We retrospectively analyzed the clinical data of patients treated with sofosbuvir plus ribavirin (SOF + RBV) or glecaprevir/pibrentasvir (G/P) for chronic HCV genotype 2 infection at seven university hospitals in the Korean southeast region.

Results: SOF + RBV therapy produced an 89% and 98.3% sustained virologic response 12 week (SVR12) after treatment completion in the full analysis set and per-protocol set, respectively, and the corresponding values for G/P therapy were 89.5% and 99.2%, respectively. The difference between the treatments was probably because 6.2% (59/953) of patients in the SOF + RBV group did not complete the treatment and 9.8% (14/143) in the G/P group did not test HCV RNA after treatment completion. Adverse events (A/Es) were reported in 59.7% (569/953) and 25.9% (37/143) of the SOF + RBV and G/P groups, respectively. In the SOF + RBV group, 12 (1.26%) patients discontinued treatment owing to A/Es, whereas no patients discontinued treatment because of A/Es in the G/P group.

Conclusion: In both treatment groups, SVR was high when treatment was completed. However, there was a high dropout rate in the SOF + RBV group, and the dropout analysis showed that these were patients with liver cirrhosis (LC; 43/285, 15.1%), especially those with decompensated LC (12/32, 37.5%). Therefore, an early initiation of antiviral therapy is recommended for a successful outcome before liver function declines. Furthermore, patients with decompensated LC who are considered candidates for SOF + RBV treatment should be carefully monitored to ensure that their treatment is completed, especially those with low hemoglobin and high alanine transaminase.
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http://dx.doi.org/10.3346/jkms.2021.36.e142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167412PMC
May 2021

The current second wave and COVID-19 vaccination status in India.

Brain Behav Immun 2021 Aug 20;96:1-4. Epub 2021 May 20.

Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si 24252, Gangwon-do, Republic of Korea. Electronic address:

Recently, India is at risk due to the exponential rising of COVID-19 infection, which generated a second wave. This infection rise may affect the vaccination program in India, and it can also affect vaccine production. In this manuscript, we have discussed the psychosocial and political factors that have driven the current wave of India. We have also tried to depict the psychosocial and political obstacles that are impairing the vaccination program.
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http://dx.doi.org/10.1016/j.bbi.2021.05.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133819PMC
August 2021

Regulation of Long-Term Courtship Memory by Ecdysis Triggering Hormone.

Front Neurosci 2021 22;15:670322. Epub 2021 Apr 22.

Neuroscience Graduate Program, University of California, Riverside, Riverside, CA, United States.

Endocrine state is an important determinant of learning and memory in animals. In , rejection of male courtship overtures by mated females leads to an aversive response manifested as courtship memory. Here we report that ecdysis triggering hormone (ETH) is an obligatory enabler of long-term courtship memory (LTM). ETH deficiency suppresses LTM, whereas augmented ETH release reduces the minimum training period required for LTM induction. ETH receptor knockdown either in the mushroom body (MB) γ lobe or in octopaminergic dorsal-anterior-lateral (DAL) neurons impairs memory performance, indicating its direct action in these brain areas. Consistent with these findings, brain exposure to ETH mobilizes calcium in MB γ lobe neuropils and DAL neurons. ETH receptor (ETHR) knockdown in the corpus allatum (CA) to create juvenile hormone (JH) deficiency also suppresses LTM, as does knockdown of the JH receptor Met in the MB γ lobe, indicating a convergence of ETH and JH signaling in this region of the brain. Our findings identify endocrine-enabled neural circuit components in the brain that are critical for persistent behavioral changes resulting from aversive social experience.
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http://dx.doi.org/10.3389/fnins.2021.670322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100193PMC
April 2021
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