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Background: Herpes simplex virus type 1 (HSV-1), known to latently infect the host’s trigeminal ganglion, can lead to severe herpes encephalitis or asymptomatic infection, potentially contributing to neurodegenerative diseases like Alzheimer’s. The virus generates reactive oxygen species (ROS) that significantly impact viral replication and induce chronic inflammation through NF-κB activation. Nuclear factor E2-related factor 2 (Nrf2), an oxidative stress regulator, can prevent and treat HSV-1 infection by activating the passive defense response in the early stages of infection. Methods and results: Our study investigated the antiviral effects of ginsenoside Rg5, an Nrf2 activator, on HSV-1 replication and several host cell signaling pathways. We found that HSV-1 infection inhibited Nrf2 activity in host cells, induced ROS/NF-κB signaling, and triggered inflammatory cytokines. However, treatment with ginsenoside Rg5 inhibited ROS/NF-κB signaling and reduced inflammatory cytokines through NRF2 induction. Interestingly, the Nrf2 inhibitor ML385 suppressed the expression of NAD(P)H quinone oxidoreductase 1(NQO1) and enhanced the expression of KEAP1 in HSV-1 infected cells. This led to the reversal of VP16 expression inhibition, a protein factor associated with HSV-1 infection, thereby promoting HSV-1 replication. Conclusion: These findings suggest for the first time that ginsenoside Rg5 may serve as an antiviral against HSV-1 infection and could be a novel therapeutic agent for HSV-1-induced neuroinflammation.

The temperature distribution inside a radiant heater for cooking purposes has not yet been fully investigated. A numerical methodology was developed to analyze the heat transfer inside a radiant heater. The numerical methodology was validated by experimental analysis, which showed close agreement for the temperature distributions of the heating coil and glass. Then, a parametric study was performed on the pitch of the heating coil, gaps in the inner coil (i.e., inner gap), and gaps in the outer coil (i.e., outer gap). The outer gap had an insignificant effect on the temperature distribution, but the coil and glass temperatures increased linearly as the pitch and inner gap were decreased. The design of the radiant heater was then optimized in terms of thermal stability. A heat loss analysis was carried out, and the numerical results showed close agreement with the experimental results in the case of 10 % heat loss. The results of this study can be used to predict the performance of a radiant heater and optimize its design.

Background Generally, an induction agent is chosen based on the conditions of the deceased donor and the recipient. Antithymocyte globulin (ATG) is preferred in relatively high-risk conditions. No clear evidence indicates which induction agent is safer or more efficient for deceased donor kidney transplantation (DDKT). This study compares the efficacy and safety of basiliximab (BSX) and ATG according to donor characteristics in DDKT. Methods A total of 724 kidney transplant recipients from three transplant centers were enrolled, and propensity score matching was performed. Based on a donor age of 60 years, donor kidney with acute kidney injury (AKI), and Kidney Donor Profile Index (KDPI) score of 65%, we investigated how the choice of induction therapy agent affected the posttransplant clinical outcomes of delayed graft function (DGF), acute rejection (AR), infectious complications, and allograft and patient survival. Results AR and DGF did not differ significantly according to induction agent in elderly/young donor, AKI/non-AKI, and high-KDPI/low-KDPI subgroups. The infection rate did not show meaningful differences. The differences in death-censored allograft survival and patient survival rates between induction agents were not statistically significant. Conclusion Our study suggests that BSX can produce clinical outcomes similarly favorable to those of ATG even in DDKT cases with relatively poor donor conditions. Nonetheless, the donor and recipient conditions, immunological risk, and infection risk must be all taken into consideration when choosing an induction agent. Therefore, clinicians should carefully select the induction therapy agent for DDKT based on the risks and benefits in each DDKT case.

The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics. Currently, neuraminidase (NA) inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration (FDA) for the prevention and treatment of influenza. Here, we show that vitisin B (VB) inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells. Reactive oxygen species (ROS), which frequently occur during viral infection, increase virus replication by activating the NF-κB signaling pathway, downmodulating glucose-6-phosphate dehydrogenase (G6PD) expression, and decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response activity. VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity, and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation. In addition, VB reduced body weight loss, increased survival, decreased viral replication and the inflammatory response in the lungs of influenza A virus (IAV)-infected mice. Taken together, our results indicate that VB is a promising therapeutic candidate against IAV infection, complements existing drug limitations targeting viral NA. It modulated the intracellular ROS by G6PD, Nrf2 antioxidant response pathway, and NF-κB signaling pathway. These results demonstrate the feasibility of a multi-targeting drug strategy, providing new approaches for drug discovery against IAV infection.

The common human coronavirus (HCoV) exhibits mild disease with upper respiratory infection and common cold symptoms. HCoV-OC43, one of the HCoVs, can be used to screen drug candidates against SARS-CoV-2. We determined the antiviral effects of FDA/EMA-approved drug anastrozole (AZ) on two human coronaviruses, HCoV-OC43 and HCoV-229E, using MRC-5 cells in vitro. The AZ exhibited antiviral effects against HCoV-OC43 and HCoV-229E infection. Subsequent studies focused on HCoV-OC43, which is related to the SARS-CoV-2 family. AZ exhibited anti-viral effects and reduced the secretion of inflammatory cytokines, TNF-α, IL-6, and IL-1β. It also inhibited NF-κB translocation to effectively suppress the inflammatory response. AZ reduced intracellular calcium and reactive oxygen species (ROS) levels, including mitochondrial ROS and Ca2+, induced by the virus. AZ inhibited the expression of NLRP3 inflammasome components and cleaved IL-1β, suggesting that it blocks NLRP3 inflammasome activation in HCoV-OC43-infected cells. Moreover, AZ enhanced cell viability and reduced the expression of cleaved gasdermin D (GSDMD), a marker of pyroptosis. Overall, we demonstrated that AZ exhibits antiviral activity against HCoV-OC43 and HCoV-229E. We specifically focused on its efficacy against HCoV-OC43 and showed its potential to reduce inflammation, inhibit NLRP3 inflammasome activation, mitigate mitochondrial dysfunction, and suppress pyroptosis in infected cells.

Influenza is an acute respiratory disorder caused by the influenza virus and is associated with prolonged hospitalization and high mortality rates in older individuals and chronically ill patients. Vaccination is the most effective preventive strategy for ameliorating seasonal influenza. However, the vaccine is not fully effective in cases of antigenic mismatch with the viral strains circulating in the community. The emergence of resistance to antiviral drugs aggravates the situation. Therefore, developing new vaccines and antiviral drugs is essential. Castanea crenata honey (CH) is an extensively cultivated food worldwide and has been used as a nutritional supplement or herbal medicine. However, the potential anti-influenza properties of CH remain unexplored. In this study, the in vitro and in vivo antiviral effects of CH were assessed. CH significantly prevented influenza virus infection in mouse Raw264.7 macrophages. CH pretreatment inhibited the expression of the viral proteins M2, PA, and PB1 and enhanced the secretion of proinflammatory cytokines and type-I interferon (IFN)-related proteins in vitro. CH increased the expression of RIG-1, mitochondrial antiviral signaling (MAVS) protein, and IFN-inducible transmembrane protein, which interferes with virus replication. CH reduced body weight loss by 20.9%, increased survival by 60%, and decreased viral replication and inflammatory response in the lungs of influenza A virus-infected mice. Therefore, CH stimulates an antiviral response in murine macrophages and mice by preventing viral infection through the RIG-1-mediated MAVS pathway. Further investigation is warranted to understand the molecular mechanisms involved in the protective effects of CH on influenza virus infection.

Abstract Background Aggregated amyloid-β (Aβ) is considered a pathogenic initiator of Alzheimer’s disease (AD), in strong association with tau hyperphosphorylation, neuroinflammation, synaptic dysfunction, and cognitive decline. As the removal of amyloid burden from AD patient brains by antibodies has shown therapeutic potential, the development of small molecule drugs inducing chemical dissociation and clearance of Aβ is compelling as a therapeutic strategy. In this study, we synthesized and screened aryloxypropanolamine derivatives and identified 1-(3-(2,4-di-tert-pentylphenoxy)-2-hydroxypropyl)pyrrolidin-1-ium chloride, YIAD002, as a strong dissociator of Aβ aggregates. Methods The dissociative activity of aryloxypropanolamine derivatives against Aβ aggregates were evaluated through in vitro assays. Immunohistochemical staining, immunoblot assays, and the Morris water maze were used to assess the anti-Alzheimer potential in YIAD002-treated 5XFAD and transgenic APP/PS1 mice. Target-ligand interaction mechanism was characterized via a combination of peptide mapping, fluorescence dissociation assays, and constrained docking simulations. Results Among 11 aryloxypropanolamine derivatives, YIAD002 exerted strongest dissociative activity against β-sheet-rich Aβ aggregates. Upon oral administration, YIAD002 substantially reduced amyloid burden and accordingly, improved cognitive performance in the Morris water maze and attenuated major pathological hallmarks of AD including tauopathy, neuroinflammation, and synaptic protein loss. Mechanism studies suggest that YIAD002 interferes with intermolecular β-sheet fibrillation by directly interacting with KLVFFA and IGLMVG domains of Aβ. In addition, YIAD002 was found to possess dissociative activity against aggregates of pyroglutamate-modified Aβ and tau. Conclusions Collectively, our results evince the potential of chemical-driven dissociation of Aβ aggregates by aryloxypropanolamines as a therapeutic modality of the amyloid clearance approach.

Herpes simplex virus 1 (HSV-1) is double-stranded DNA virus that belongs to the Orthoherpesviridae family. It causes serious neurological diseases of the central nervous system, such as encephalitis. The current U.S. Food and Drug Administration (FDA)-approved drugs for preventing HSV-1 infection include acyclovir (ACV) and valacyclovir; however, their long-term use causes severe side effects and often results in the emergence of drug-resistant strains. Therefore, it is important to discover new antiviral agents that are safe and effective against HSV-1 infection. Korean chestnut honey (KCH) has various pharmacological activities, such as antioxidant, antibacterial, and anti-inflammation effects; however, antiviral effects against HSV-1 have not yet been reported. Therefore, we determined the antiviral activity and mechanism of action of KCH after HSV-1 infection on the cellular level. KCH inhibited the HSV-1 infection of host cells through binding and virucidal steps. KCH decreased the production of reactive oxygen species (ROS) and calcium (Ca2+) following HSV-1 infection and suppressed the production of inflammatory cytokines by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кB) activity. Furthermore, we found that KCH inhibited the expression of the nod-like receptor protein 3 (NLRP3) inflammasome during HSV-1 infection. Taken together, the antiviral effects of KCH occur through multiple targets, including the inhibition of viral replication and the ROS-mediated NLRP3 inflammasome pathway. Our findings suggest that KCH has potential for the treatment of HSV-1 infection and related diseases.

Influenza viruses cause respiratory infections in humans with high morbidity and mortality rates. Neuraminidase inhibitors such as oseltamivir and peramivir are the most commonly used drugs for influenza virus infections. However, the emergence of resistant viruses necessitates the urgent need to develop next-generation anti-influenza drugs. Soybean (Glycine max L. Merr.) is widely cultivated and used as food worldwide. In addition, soybean has long been used as a nutritional supplement and herbal medicine. However, the potential anti-influenza properties of the soybean cultivar “GL 2626/96″ (SG2626) are yet to be investigated. Herein, we determined whether the ethanolic extract of SG2626 (SG2626E) has anti-viral activity through performing SG2626E pre-, co-, and post-treatment assays, using the influenza green fluorescent protein (GFP)-tagged influenza A/PR/8/34 (A/PR/8/34-GFP) virus. SG2626E showed anti-influenza virus activity in pre- and co-treated cells in a dose-dependent manner, but not in post-treated cells. SG2626E imparted a considerable inhibitory effect on influenza A virus (IAV) infection through blocking viral attachment. SG2626E inhibited the activity of viral hemagglutinin, but not viral neuraminidase of the IAV. SG2626E inhibited IAV infection by reducing intracellular calcium levels in infected human lung epithelial A549 cells. Additionally, SG2626E reduced body weight loss, decreased mortality, and increased the survival rate through reducing viral replication in the lungs of IAV-infected mice. Overall, these results suggest that SG2626E inhibits IAV infection and is a potential novel anti-influenza agent.

Background : We investigated whether the development of delayed graft function (DGF) in pre-sensitized patients affects the clinical outcomes after deceased-donor kidney transplantation (DDKT). Methods : The study included 709 kidney transplant recipients (KTRs) from three transplant centers. We divided KTRs into four subgroups (highly sensitized DGF, highly sensitized non-DGF, low-sensitized DGF, and low-sensitized non-DGF) according to panel reactive antibody level of 50%, or DGF development. We compared post-transplant clinical outcomes among the four subgroups. Results : Incidence of biopsy-proven acute rejection (BPAR) was higher in two highly sensitized subgroups than in low-sensitized subgroups. It tended to be higher in highly sensitized DGF subgroups than in the highly sensitized non-DGF subgroups. In addition, the highly sensitized DGF subgroup showed the highest risk for BPAR (hazard ratio, 3.051; P=0.005) and independently predicted BPAR. Allograft function was lower in the two DGF subgroups than in the non-DGF subgroup until one month after transplantation, but thereafter it was similar. Death-censored graft loss rates and patient mortality tended to be low when DGF developed, but it did not reach statistical significance. Conclusions: DGF development in highly sensitized patients increases the risk for BPAR in DDKT compared with patients without DGF, suggesting the need for strict monitoring and management of such cases.

Abstract Purpose Disruption of the tumor-brain barrier in meningioma is a crucial factor in peritumoral brain edema (PTBE). We previously reported the possible effect of osteoporosis on the integrity of the arachnoid trabeculae because both the bone and the arachnoid trabeculae are composed of type 1 collagen. We hypothesized that osteoporotic conditions may be associated with PTBE occurrence after radiation treatment in patients with meningioma. Methods A receiver operating characteristic curve analysis was used to identify the optimal cut-off values of mean skull Hounsfield unit for predicting osteopenia and osteoporosis in patients from our registry. Multivariate Cox regression analysis was used to determine whether possible osteoporosis independently predicted PTBE development in patients with meningioma after radiation. Results A total of 106 intracranial meningiomas were included for the study. All patients received linear accelerator-based radiation therapy in our hospital over an approximate 6-year period. Multivariate Cox regression analysis identified that hypothetical osteoporosis was an independent predictive factor for the development of PTBE in patients with meningioma after linear accelerator-based radiation treatment (hazard ratio 5.20; 95% confidence interval 1.11–24.46; p = 0.037). Conclusions Our study suggests that possible osteoporotic conditions may affect PTBE development after linear accelerator-based radiation treatment for intracranial meningioma. However, due to the study’s small number of patients, these findings need to be validated in future studies with larger cohorts, before firm recommendations can be made. Graphic abstract

Recently, attention has focused on the prevention and treatment of respiratory viruses including influenza viruses. We evaluated the antiviral effect of Tilia amurensis honey (TH) against influenza A virus in murine macrophages. Influenza A virus infection was reduced following pretreatment with TH. Pretreatment of murine macrophages with TH increased the production and secretion of type-1 interferon (IFN) and proinflammatory cytokines and increased phosphorylation of the type-1 IFN-related proteins, TANK-binding kinase (TBK), and STAT. Moreover, TH increased the expression of IFN-stimulating genes and increased the expression of IFN-inducible transmembrane (IFITM3), a protein that interferes with virus replication and entry. Taken together, these findings suggest that TH suppresses influenza A virus infection by regulating the innate immune response in macrophages. This supports the development of preventive and therapeutic agents for influenza A virus and enhances the economic value of TH.

Kamut sprouts (KaS) contain several biologically active compounds. In this study, solid-state fermentation using Saccharomyces cerevisiae and Latilactobacillus sakei was used to ferment KaS (fKaS-ex) for 6 days. The fKaS-ex showed a 26.3 mg/g dried weight (dw) and 46.88 mg/g dw of polyphenol and the β-glucan contents, respectively. In the Raw264.7 and HaCaT cell lines, the non-fermented KaS (nfKaS-ex) decreased cell viability from 85.3% to 62.1% at concentrations of 0.63 and 2.5 mg/mL, respectively. Similarly, the fKaS-ex decreased cell viability, but showed more than 100% even at 1.25 and 5.0 mg/mL concentrations, respectively. The anti-inflammatory effect of fKaS-ex also increased. At 600 µg/mL, the fKaS-ex exhibited a significantly higher ability to reduce cytotoxicity by suppressing COX-2 and IL-6 mRNA expressions as well as that for IL-1β mRNA. In summary, fKaS-ex exhibited significantly lower cytotoxicity and increased anti-oxidant and anti-inflammatory properties, indicating that fKaS-ex is beneficial for use in food and other industries.

Background This study evaluated the impact of acute kidney injury (AKI) on posttransplant clinical outcomes for deceased donor (DD) kidney transplantation (KT) using the Kidney Donor Profile Index (KDPI) system. Methods Overall, 657 kidney transplant recipients (KTRs) receiving kidneys from 526 DDs from four transplant centers were included. We divided them into the high and low KDPI donor groups by 65%, the KDPI score, and both groups were subdivided into the AKI-DDKT and non-AKI-DDKT subgroups according to AKI in DDs. Results There was no significant difference in the incidence of delayed graft function (DGF) between the high and low KDPI-KTR groups; however, the AKI-DDKT subgroup showed significantly higher incidence of DGF than the non-AKI-DDKT subgroup in both groups (p = 0.001, p < 0.001, respectively). The death-censored graft survival rate was significantly lower in the high KDPI-KTR group than in the low KDPI-KTR group (p = 0.005). Only in the high KDPI-KTR group, the death-censored graft survival rate was significantly lower in the KT from DDs with AKI stage 3 than KT from DDs with non-AKI or AKI stage 1 or 2 (p = 0.040). The interaction between AKI stage 3 in DDs and high KDPI on the allograft outcome was significant (p = 0.002). Conclusion KTs from DDs with AKI stage 3 showed an adverse impact on the allograft outcome in the high KDPI-KTR group. Therefore, DDs with a high KDPI score should be managed carefully so that severe AKI does not occur prior to KT.

Abstract Bacillus genus produces several secondary metabolites with biocontrol ability against various phytopathogens. Bacillus velezensis AK-0 (AK-0), an antagonistic strain isolated from Korean ginseng rhizospheric soil, was found to exhibit antagonistic activity against several phytopathogens. To further display the genetic mechanism of the biocontrol traits of AK-0, we report the complete genome sequence of AK-0 and compared it with complete genome sequences of closely related strains. We report the biocontrol activity of AK-0 against apple bitter rot caused by Colletotrichum gloeosporioides, which could lead to commercialization of this strain as a microbial biopesticide in Korea. To retain its biocontrol efficacy for a longer period, AK-0 has been formulated with ingredients for commercialization, named AK-0 product formulation (AK-0PF). AK-0PF played a role in the suppression of the mycelial growth of the fungicide-resistant pathogen C. gloeosporioides YCHH4 at a greater level than the non-treated control. Moreover, AK-0PF exhibited greater disease suppression of bitter rot in matured under field conditions. Here, we report the complete genome sequence of the AK-0 strain, which has a 3,969,429 bp circular chromosome with 3808 genes and a G+C content of 46.5%. The genome sequence of AK-0 provides a greater understanding of the Bacillus species, which displays biocontrol activity via secondary metabolites. The genome has eight potential secondary metabolite biosynthetic clusters, among which, ituD and bacD genes were expressed at a greater level than other genes. This work provides a better understanding of the strain AK-0, as an effective biocontrol agent (BCA) against phytopathogens, including bitter rot in apple.

Abstract A novel deep-learning algorithm for artificial neural networks (ANNs), completely different from the back-propagation method, was developed in a previous study. The purpose of this study was to assess the feasibility of using the algorithm for the detection of intracranial haemorrhage (ICH) and the classification of its subtypes, without employing the convolutional neural network (CNN). For the detection of ICH with the summation of all the computed tomography (CT) images for each case, the area under the ROC curve (AUC) was 0.859, and the sensitivity and the specificity were 78.0% and 80.0%, respectively. Regarding ICH localisation, CT images were divided into 10 subdivisions based on the intracranial height. With the subdivision of 41–50%, the best diagnostic performance for detecting ICH was obtained with AUC of 0.903, the sensitivity of 82.5%, and the specificity of 84.1%. For the classification of the ICH to subtypes, the accuracy rate for subarachnoid haemorrhage (SAH) was considerably excellent at 91.7%. This study revealed that our approach can greatly reduce the ICH diagnosis time in an actual emergency situation with a fairly good diagnostic performance.

Abstract Background The blood-brain barrier has been a hindrance to developing blood-based diagnostic tests for dementias, as it limits the appearance of brain biomarkers in the blood. Our aim was to see if the natural opening of the blood-brain barrier induced by ischemic stroke would increase serum levels of inflammatory biomarkers known to be elevated in the brains of patients with Alzheimer’s disease and other neurodegenerative dementias. Methods Forty-three patients with acute ischemic stroke presenting to Stony Brook University Hospital were prospectively enrolled in the study. Eight of these patients were clinically diagnosed as having an underlying neurodegenerative dementia. Blood was drawn acutely within 72 h of stroke symptom onset, and serum levels of the classic inflammatory biomarkers, interleukin-6 (IL-6) and C-reactive protein (CRP) were measured, along with levels of S100B protein (S100B) and complement C3 (CC3). Results Serum levels of IL-6 and CRP in patients with acute ischemic stroke and underlying dementia (AIS + D) were significantly higher (p = 0.002 and 0.003, respectively) than in patients with acute ischemic stroke alone (AIS). Serum levels of S100B and CC3 did not differ significantly between the groups. Conclusions This study supports the possibility that opening of the blood-brain barrier may enhance the blood appearance of brain tissue markers of inflammation associated with neurodegenerative dementia. Further study is warranted to test this possibility, given the recent emergence of methods to open the blood-brain barrier for diagnostic or therapeutic purposes.

Red pepper, one of the major economic crops in Korea, is being affected by anthracnose disease caused by Colletotrichum acutatum. To control this disease, an antagonistic bacterial strain, Bacillus subtilis YGB36 identified by 16S rDNA sequencing, physiological and biochemical analyses is used as a biological control agent. In vitro screening revealed that the strain YGB36 possess strong antifungal activity against the pathogen Cylindrocarpon destructans. The strain exhibited cellulase, protease, amylase, siderophore production and phosphate solubility. In vitro conidial germination of C. acutatum was most drastically inhibited by YGB36 cell suspensions (106 cfu/ml) or culture filtrate. Development of anthracnose symptoms was reduced on detached immature green pepper fruits by treatment with cell suspensions, and its control value was recorded as 65.7%. The YGB36 bacterial suspension treatment enhanced the germination rate of red pepper seeds and promoted root development and growth under greenhouse conditions. The in vitro screening of fungicide and insecticide sensitivity test against YGB36 revealed that the bacterial growth was not affected by any of the insecticides, and 11 fungicides out of 21 used. Collectively, our results clearly suggest that the strain YGB36 is considered as one of the potential biocontrol agents against anthracnose disease in red pepper.

During the year 2018, the symptoms of bunch rot on Shine Muscat (Vitis vinifera L.) were observed in Kimcheon-si, Gyeongbuk province in Korea. The disease appears on the Shine Muscat as a black rot due to prolific fungal sporulation after it has invaded into the Shine Muscat which look completely empty and dryness. Colonies of these fungi are present on the Shine Muscat skin from fruit setting and increase in amount from early season to harvest, while become peak at ripening stage. To isolate the causal agent, small fragments (2 to 3 mm) of decayed tissue from the lesion margin were placed onto potato dextrose agar (PDA) plates. Fungal colonies on PDA produced dense white aerial mycelium and then covered with dark black conidial heads. These heads were large and radiate, and vesicles were globose (2.12–32.0×2.0–3.1 μm). Based on morphological and cultural characteristics, this fungus was identified as Aspergillus tubingensis. To confirm its identity, the internal transcribed spacer, β-tubulin, and RNA polymerase II was sequenced for molecular identification. BLAST search indicated 99% identity with A. tubingensis. The pathogenicity test on healthy grape of Shine Muscat produced bunch rot, as the original symptoms. To select effective fungicides for the control of brunch rot, an in vitro antifungal activity of seven fungicides were evaluated against the growth of A. tubingensis. Five fungicides (dipenoconazole, tebuconazole, metconazole, iminoctadine, and captan) exhibited significantly strong suppression of the mycelial growth of A. tubingensis.

Susceptible host plants challenged by fungal pathogens can display different types of lesions, which can be attributed to environmental factors affecting the nature of interactions between the host and pathogen. During our survey of apple anthracnose in Korea, two distinct types of disease symptoms, designated as progressive (PS) and static symptoms (SS), were recognized. PS is a typical, rapidly enlarging symptom of apple anthracnose, while SS is a small, dark speck that does not expand further until the harvesting season. Isolation and genotyping of pathogens from disease lesions suggested that all of them belong to Colletotrichum gloeosporioides, a well-known causal agent of apple anthracnose. Two types of isolates were comparable in growth on media, spore germination and appressorium formation, virulence test on fruits at various temperature conditions. Furthermore, they were analyzed at the molecular level by a phylogenetic tree, RNA-seq, and expression of virulence gene. However, the SS isolates were defective in appressorium-mediated penetration into the underlying substratum. RNA-seq analysis of PS and SS isolates showed that distinct transcriptional programs underlie the development of different types of anthracnose symptoms in host plants. One downregulated gene in SS encoded isocitrate lyase is essential for disease development via its involvement in the glyoxylate cycle. It partly explains why SS is less virulent than PS on host plants. Overall, our work challenges the traditional view on the development of different lesion types and provides valuable insights into variations that exist in the pathogen population.

OCD20015-V009 is an herbal mix of water-extracted Ginseng Radix, Poria (Hoelen), Rehmanniae Radix, Adenophorae Radix, Platycodi Radix, Crataegii Fructus, and Astragali Radix. In this study, its in vitro and in vivo antiviral activity and mechanisms against the influenza A virus were evaluated using a GFP-tagged influenza A virus (A/PR/8/34-GFP) to infect murine macrophages. We found that OCD20015-V009 pre-treatment substantially reduced A/PR/8/34-GFP replication. Also, OCD20015-V009 pre-treatment increased the phosphorylation of type-I IFN-related proteins TBK-1 and STAT1 and the secretion of pro-inflammatory cytokines TNF-α and IL-6 by murine macrophages. Moreover, OCD20015-V009 prophylactic administration increased IFN-stimulated genes-related 15, 20, and 56 and IFN-β mRNA in vitro. Thus, OCD20015-V009 likely modulates murine innate immune response via macrophages. This finding is potentially useful for developing prophylactics or therapeutics against the influenza A virus. Furthermore, pre-treatment with OCD20015-V009 decreased the mortality of the mice exposed to A/PR/8/34-GFP by 20% compared to that in the untreated animals. Thus, OCD20015-V009 stimulates the antiviral response in murine macrophages and mice to viral infections. Additionally, we identified chlorogenic acid and ginsenoside Rd as the antiviral components in OCD20015-V009. Further investigations are needed to elucidate the protective effects of active components of OCD20015-V009 against influenza A viruses.

There has been an immense effort by global pharmaceutical companies to develop anti-COVID-19 drugs, including small molecule-based RNA replication inhibitors via drug repositioning and antibody-based spike protein blockers related to cell entry by SARS-CoV-2. However, several limitations to their clinical use have emerged in addition to a lack of progress in the development of small molecule-based cell entry inhibitors from natural products. In this study, we tested the effectiveness of kuwanon C (KC), which has mainly been researched using in silico docking simulation and can serve as an effective building block for developing anti-COVID-19 drugs, in blocking the spike S1 RBD:ACE2 receptor interaction. KC is a natural product derived from Morus alba L., commonly known as mulberry, which has known antiviral efficacy. Molecular interaction studies using competitive ELISA and the BLItz system revealed that KC targets both the spike S1 RBD and the ACE2 receptor, successfully disrupting their interaction, as supported by the in silico docking simulation. Furthermore, we established a mechanism of action by observing how KC prevents the infection of SARS-CoV-2 spike pseudotyped virus in ACE2/TPRSS2-overexpressing HEK293T cells. Finally, we demonstrated that KC inhibits clinical isolates of SARS-CoV-2 in Vero cells. Future combinations of small molecule-based cell entry inhibitors, such as KC, with the currently prescribed RNA replication inhibitors are anticipated to significantly enhance the efficacy of COVID-19 therapies.

Despite the recent development of RNA replication-targeted COVID-19 drugs by global pharmaceutical companies, their prescription in clinical practice is limited by certain factors, including drug interaction, reproductive toxicity, and drug resistance. COVID-19 drugs with multiple targets for the SARS-CoV-2 life cycle may lead to a successful reduction in drug resistance as well as enhanced therapeutic efficacy, and natural products are a potential source of molecules with therapeutic effects against COVID-19. In this study, we investigated the inhibitory efficacy of mulberrofuran G (MG), a component of Morus alba L., also known as mulberry, which has been used as food and traditional medicine, on the binding of the spike S1 receptor-binding domain (RBD) protein to the angiotensin-converting enzyme 2 (ACE2) receptor, which is the initial stage of the SARS-CoV-2 infection. In competitive enzyme-linked immunosorbent assays, MG effectively blocked the spike S1 RBD: ACE2 receptor molecular binding, and investigations using the BLItz system and in silico modeling revealed that MG has high affinity for both proteins. Finally, we confirmed that MG inhibits the entry of SARS-CoV-2 spike pseudotyped virus and a clinical isolate of SARS-CoV-2 into cells, suggesting that MG might be a promising therapeutic candidate for preventing SARS-CoV-2 binding to the cell surface during early infection.

Immune checkpoints such as programmed death-1 (PD-1) have been proven as antitumor targets by enhancing cytotoxic T cell activity. All immune checkpoint blockades are antibody therapeutics that have large size and high affinity, as well as known immune-related side effects and low responses. To overcome the limitation of antibody therapeutics, we have explored PD-1/PD-L1 (programmed death-ligand 1) blockades in traditional oriental medicine, which has a long history but has not yet studied PD-1/PD-L1 blockades. Sanguisorbae Radix extract (SRE) blocked PD-1 and PD-L1 binding in competitive ELISA. SRE effectively inhibited the PD-1/PD-L1 interaction, thereby improving T cell receptor (TCR) signaling and the NFAT-mediated luciferase activity of T cells. SRE treatment reduced tumor growth in the humanized PD-L1 MC38 cell allograft humanized PD-1 mouse model. Additionally, the combination of SRE and pembrolizumab (anti-PD-1 antibody) suppressed tumor growth and increased infiltrated cytotoxic T cells to a greater extent did either agent alone. This study showed that SRE alone has anticancer effects via PD-1/PD-L1 blockade and that the combination therapy of SRE and pembrolizumab has enhanced immuno-oncologic effects.

Background At most centers, general anesthesia (GA) has been preferred for endovascular treatment (EVT) of ruptured intracranial aneurysms (RIAs). In this study, we analyzed procedural results, clinical outcomes, and follow-up angiographic findings for patients undergoing EVT for RIA under local anesthesia (LA) with conscious sedation (CS). Methods We retrospectively evaluated 308 consecutive patients who underwent EVT for RIAs at a single institution between June 2009 and February 2017. EVT under LA with CS was considered for all patients with aneurysmal subarachnoid hemorrhage, regardless of Hunt and Hess (HH) scale score. Results EVT was performed for 320 aneurysms in 308 patients with subarachnoid hemorrhages. The mean patient age was 55.5±12.6 years. Moderate (III) and poor (IV, V) HH grades were observed in 75 (24.4%) and 77 patients (25%), respectively. Complete occlusion immediately after EVT was achieved for 270 (84.4%) of 320 aneurysms. Thromboembolic complications and intraprocedural ruptures occurred in 25 (7.8%) and 14 cases (4.3%), respectively. The morbidity rate at discharge (as defined by a modified Rankin scale score of 3 or greater) was 27.3% (84/308), while the mortality rate was 11.7% (36/308). Follow-up angiographic results were available for 210 (68.1%) of 308 patients. Recanalization was observed in 64 (29.3%) of 218 aneurysms in 210 patients. Conclusion Based on our experience, EVT for RIAs under LA with CS was feasible, regardless of the clinical grade of the subarachnoid hemorrhage. Complication rates and follow-up angiographic results were also comparable to those observed when GA was used to perform the procedure.

Herpes simplex Type 1 (HSV-1) is a neurotropic virus that infects the peripheral and central nervous system. Usually, after primary infection in epithelial cells, HSV-1 migrates retrograde to the peripheral nervous system (PNS), where it establishes a latent infection. HSV-1 can remain latent in the nervous system, and its reactivation in the brain can rarely cause acute HSV-1 encephalitis, often a life-threatening condition, or asymptomatic reactivations that could lead to neuronal damage and ultimately neurodegenerative disorders. Acyclovir and related nucleoside analogs have been used as therapeutic agents for HSV-1 infection, but resistance to the drug can arise, and the protective effect of HSV-1 on brain cells is limited. Therefore, there is an urgent need for research into safe and effective new antiviral agents that can protect brain cells from the damage that is caused by HSV-1 infection. Vaccinium bracteatum Thunb. (VBT) is widely distributed in Korea and China, and has pharmacological actions such as anti-inflammatory, antioxidant, and antidiabetic activity. Studies on the antiviral effect of VBT on HSV-1 infection have not been reported so far. Therefore, we sought to determine the HSV-1 antiviral effect and molecular mechanism of VBT at the cellular level. We confirmed that VBT repressed the VP16 and IE genes in both Vero and SK-N-SH cells. We also found that the generation of HSV-1 virions was inhibited by VBT treatment. VBT inhibited the activities of the HSV-1-induced endoplasmic reticulum (ER) stressors PERK, ATF4, and CHOP. We confirmed that VBT inhibited the activity of apoptosis factors by regulating the expression of death receptor (DR) after HSV-1 infection. As HSV-1 is closely associated with brain diseases, the study of the antiviral drug effects and mechanism of VBT is meaningful. Further studies using animal models of infection will also be performed to determine the potential of VBT as an antiviral agent.

Background:. The temporoparietal fascia (TPF) flap has been successfully used in the treatment of microtia with primary or secondary cases. The literature contains numerous studies about its structure and vascular anatomy in adults. However, it is rare to study its vasculature and characteristics in children. Methods:. From September of 2013 to May of 2020, 188 patients with average age of 9.8 years (range, 5–14 years) underwent total ear reconstruction with costal cartilage in 67 patients (68 ears) or porous polyethylene framework in 121 patients (128 ears) using 196 TPF flaps. The TPF flap was most commonly used in second-stage operations to elevate the reconstructed auricle in the costal cartilage group. Contrastingly, the TPF flap was routinely used in the porous polyethylene framework group. The vascular pattern and characteristics of the TPF flap were evaluated during flap elevation. Results:. Only 140/196 cases (71.4%) showed a typical pattern with the superficial temporal artery and the superficial temporal vein in this study; others (28.6%) were supplied by combinations of the posterior auricular artery or vein, occipital vein, diploic vein, and superficial artery or vein. Meanwhile, there are variants of the STA and posterior origin-superficial temporal artery, which originates posterior to the lobule beneath the cartilage remnant (3/196, 1.5%). Conclusion:. Surgeons should inspect the pattern of the TPF flap thoroughly before elevation in children, because of the variety of the vessels and anatomic patterns of TPF.

Abstract Influenza viruses are a serious threat to human health, causing numerous deaths and pandemics worldwide. To date, neuraminidase (NA) inhibitors have primarily been used to treat influenza. However, there is a growing need for novel NA inhibitors owing to the emergence of resistant viruses. Geranii Herba (Geranium thunbergii Siebold et Zuccarini), which is edible, has long been used in a variety of disease treatments in Asia. Although recent studies have reported its various pharmacological activities, the effect of Geranii Herba and its components on influenza viruses has not yet been reported. In this study, Geranii Herba ethanol extract (GHE) and its component geraniin showed high antiviral activity against influenza A strain as well as influenza B strain, against which oseltamivir has less efficacy than influenza A strain, by inhibiting NA activity following viral infection in Madin–Darby canine kidney cells. Thus, GHE and its components may be useful for the development of anti-influenza drugs.

Objective Percutaneous cervical nucleoplasty (PCN) is used to treat cervical disc herniation. Radiological imaging studies, including plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI), have been used to make early predictions of cervical spinal surgery outcomes. However, simple radiological studies do not provide sufficiently detailed information; moreover, CT and MRI are highly expensive. Herein, we aimed to elucidate the usefulness of digital infrared thermography imaging (DITI) as an outcome marker after cervical nucleoplasty by correlating the changes in thermal difference (ΔTD) with the changes in pain intensity after PCN expressed as visual analogue scale (ΔVAS) scores. Methods For this study, 255 patients treated with PCN at Thomas Hospital between March 2012 and August 2014 were included. For each patient, demographic and clinical data, including preoperative MRI results, ΔVAS, ΔTD at the disc level treated with PCN, subjective symptom improvement, procedure-related discomfort, overall satisfaction, and adverse effects, were collected and evaluated for up to 3 months retrospectively. Results Thermal difference (TD) and VAS scores improved after PCN (p

Abstract Background The problem of organ shortage is an important issue in kidney transplantation, but the effect of kidney donation on AKI is unclear. The aim of this study was to investigate the impact of acute kidney injury (AKI) on post-transplant clinical outcomes for deceased donor kidney transplantation (DDKT) using standard criteria donors (SCDs) versus expanded criteria donors (ECDs). Methods Five-hundred nine KT recipients receiving kidneys from 386 deceased donors (DDs) were included from three transplant centers. Recipients were classified into the SCD-KT or ECD-KT group according to corresponding DDs and both groups were divided into the AKI-KT or non-AKI-KT subgroups according to AKI in donor. We compared the clinical outcomes among those four groups and investigated the interaction between AKI in donors and ECD on allograft outcome. Results The incidence of delayed allograft function was higher when the donors had AKI within SCD-KT and ECD-KT groups. In allograft biopsies within 3 months, chronic change was more significant in the AKI-ECD-KT subgroup than in the non-AKI-ECD-KT subgroup, but it did not differ between AKI-SCD-KT and non-AKI-SCD-KT group. AKI-ECD-KT showed higher risk for death-censored allograft failure than the other three groups and a significant interaction was observed between AKI in donors and ECD on the allograft outcome. Conclusions The presence of AKI in ECDs significantly impacted the long-term allograft outcomes of kidney transplant recipients, but it did not in SCDs.

Understanding the morphology of the acetabulum is necessary for preoperative evaluation in hip surgery. The purpose of this study was to (1) establish a novel method for measuring three-dimensional (3D) acetabular orientation, (2) quantify the reliability of this method, and (3) describe relevant characteristics of three-dimensional (3D) acetabular orientation among normal Asian subjects. Computed tomography (CT) scans of the pelvis that had been performed for suspected non-musculoskeletal conditions were obtained from 200 subjects (60 males, 140 females). A novel method was developed to measure 3D acetabular orientation with a semi-automatically determined pelvic coordinate system based on the anterior pelvic plane (APP). To quantify the robustness of our method, we analyzed the results obtained from 20 patients at different times and with different raters and pelvic poses in the same CT volume. To determine morphological differences of the acetabulum by age and sex, we analyzed the parameters of 200 CT volumes. Each intraclass correlation coefficient (ICC) values for intra- and inter-observer reliability were over 0.975 and 0.945, demonstrating high reliability. Furthermore, agreement between the angles determined from the original volume and the rotated volume was nearly perfect (ICCs > 0.956). Multiple linear regression analysis with age and sex as covariates indicated that acetabular inclination was not significantly associated with age (p = 0.687) or sex (p = 0.09). There was also no evidence that acetabular anteversion was associated with age (p = 0.383) or sex (p = 0.53). Our method showed excellent reliability for determining acetabular orientation, as it is robust, fast, and easily applicable to larger populations. In addition, the results of the analysis of acetabular orientation by age and sex can be used as a reference in various diagnostic procedures in orthopedics.

In August of 2011, a wilting disease of ginseng was observed at Bongwha, Gyeongbuk province, Korea. Affected plants initially show withering symptoms on leaves of ginseng. As the disease progresses, withering leaves spread downward, eventually encompassing the whole plant. Leaves lose vigor but remain pale green. Symptoms of roots were brown, and soft rots characterized by moist and watery decay of the whole ginseng root, which initiated as small brown, water-soaked lesions of hairy roots and enlarged to the entire roots. The causal organism isolated from the infected roots was identified as Serratia plymuthica based on its physiological and biochemical characteristics, by cellular fatty acid composition (GC-FAME), the utilization of carbon sources (BioLog System), and 16S rRNA sequence of the isolated bacterium were 99% homologous to those of Serratia plymuthica strains. Artificial inoculation of the bacterium produced the same brown or soft rot symptoms on the ginseng roots, from which the same bacterium was isolated. This is the first report of bacterial root rot caused by the Serratia plymuthica in ginseng in Korea. Serratia plymuthica has been used as antagonistic microorganism for biological control on several crop plants. But it was proved pathogen of ginseng at humid condition in this study.

In 2018, symptoms of black rot on apple (Malus pumila var. dulcissima KOIDZ) cv. Fuji were observed in Yeongcheon-si, Korea. The fruit decay symptoms consisted of purple pimples spots, black rot around the seed cavity (calyx end), mummified fruit. To isolate the causal agent, small fragment (2 to 3 mm) of decayed tissue from the lesion margin were placed on WA or PDA. Fungal colonies on PDA produced dense white aerial mycelium, becoming dark gray with age. Pycnidia and conidia were observed under a light microscopy. The shapes of conidia were aseptate, ovoid, rounded at both ends, and 21.7-28.3 × 9.9-15.3 um. Based on morphological and cultural characteristics, this fungus was identified as Diplodia seriata. To confirm its identity, two loci (ITS and β-tubulin) were sequenced for molecular identification. BLAST searches indicated 100% identity with D. seriata. A pathogenicity test was conducted with isolates on Fuji apples. The apples were inoculated with mycelial plugs (5 mm) from 7-day-old cultures of the putative pathogens. All inoculated apples developed rot symptoms identical to the original symptoms, from which D. seriata were reisolated, fulfilling Koch’s postulates. This study is the first report of black rot caused Diplodia seriata on apple.

Objectives To investigate the chronological patterns of diseases in Northern Gyeonggi-do province, South Korea, and compare these with national data. Methods A National Health Insurance cohort based on the National Health Information Database (NHID Cohort 2002–2013) was used to perform a retrospective, population-based study (46,605,433 of the target population, of which 1,025,340 were randomly sampled) to identify disease patterns from 2002 to 2013. Common diseases including malaria, cancer (uterine cervix, urinary bladder, colon), diabetes mellitus, psychiatric disorders, hypertension, intracranial hemorrhage, bronchitis/bronchiolitis, peptic ulcer, and end stage renal disease were evaluated. Results Uterine cervix cancer, urinary bladder cancer and colon cancer had the greatest rate of increase in Northern Gyeonggi-do province compared with the rest of the country, but by 2013 the incidence of these cancers had dropped dramatically. Acute myocardial infarction and end stage renal disease also increased over the study period. Psychiatric disorders, diabetes mellitus, hypertension and peptic ulcers showed a gradual increase over time. No obvious differences were found for intracranial hemorrhage or bronchitis/bronchiolitis between the Northern Gyeonggi-do province and the remaining South Korean provinces. Malaria showed a unique time trend, only observed in the Northern Gyeonggi province, peaking in 2004, 2007 and 2009 to 2010. Conclusion This study showed that the Northern Gyeonggi-do province population had a different disease profile over time, compared with collated data for the remaining provinces in South Korea. “Big data” studies using the National Health Insurance cohort database can provide insight into the healthcare environment for healthcare providers, stakeholders and policymakers.

Immune checkpoint inhibitors, increasingly used to treat malignant tumors, are revolutionizing cancer treatment by improving the patient survival expectations. Despite the high antitumor efficacy of antibody therapeutics that bind to PD-1/PD-L1, study on small molecule-based PD-1/PD-L1 inhibitors is required to overcome the side effects of antibody therapeutics caused by their size and affinity. Herein, we investigated antitumor potential of Salvia plebeia R. Br. extract (SPE), which has been used as a traditional oriental medicine and food in many countries, and its components by the blockade of PD-1/PD-L1 interaction. SPE and its component cosmosiin effectively blocked the molecular interaction between PD-1 and PD-L1. SPE also inhibited tumor growth by increasing CD8+ T-cells in the tumor through the activation of tumor-specific T-cells in a humanized PD-1 mouse model bearing hPD-L1 knock-in MC38 colon adenocarcinoma tumor. This finding presents a preclinical strategy to develop small molecule-based anticancer drugs targeting the PD-1/PD-L1 immune checkpoint pathway.

BACKGROUND AND PURPOSE:Disruption of the tumor-brain barrier in meningioma plays a critical role in the development of peritumoral brain edema (PTBE). We hypothesized that osteoporotic conditions may be associated with PTBE occurrence after radiation in patients with intracranial meningioma. METHODS:We measured Hounsfield units (HU) of the frontal skull on simulation brain CT in patients who underwent linear accelerator (LINAC)-based radiation treatment for intracranial meningioma. Receiver operating characteristic curve analysis was performed to determine the optimal cut-off values for several predictive factors. The cumulative hazard for PTBE was estimated and classified according to these factors. Hazard ratios were then estimated to identify independent predictive factors associated with the development of PTBE after radiation in intracranial meningioma patients. RESULTS:A total of 83 intracranial meningiomas in 76 patients who received LINAC-based radiation treatment in our hospital over an approximate 5-year period were included for the study. We found mean frontal skull HU ≤630.625 and gross tumor volume >7.194 cc to be independent predictors of PTBE after radiation treatment in patients with meningioma (hazard ratio, 8.41; P = 0.019; hazard ratio, 5.92; P = 0.032, respectively). In addition, patients who were ≥65 years showed a marginally significant association with PTBE. CONCLUSIONS:Our study suggests that possible osteoporotic conditions, large tumor volume, and older age may be associated with PTBE occurrence after LINAC-based radiation treatment for intracranial meningioma. In the future we anticipate that these findings may enhance the understanding of the underlying mechanisms of PTBE after radiation in meningioma patients.

Background Critical limb ischemia has been identified as a risk factor for the incidence of postoperative delirium in elderly patients. Limb amputation is the last option in critical limb ischemia treatments. We investigated the incidence and predisposing factors of postoperative delirium in patients undergoing major leg amputation. Methods From January 2012 to December 2016, 121 patients aged over 60 years who had undergone major leg amputation were enrolled in this study. Various factors related to the patients’ outcomes were assessed, including demographic, preoperative laboratory, anesthetic, surgical, and postoperative indicators. Results Twenty two patients were excluded and 99 patients were assigned to either the delirium group or no delirium group. Forty of them (40%) developed a delirium during 30 days postoperatively. Univariate analysis implied that end-stage renal disease on hemodialysis, alcohol consumption, C-reactive protein, staying in an intensive care unit (ICU), duration of an ICU stay, occurrence of complications, and mortality during six months, were the factors that accounted for significant differences between the two groups. In multivariate analysis, three factors were significantly related to the development of delirium: mortality during six months (odds ratio [OR] = 13.86, 95% CI [2.10–31.90]), alcohol (OR = 8.18, 95% CI [1.13–16.60]), and hemodialysis (OR = 4.34, 95% CI [2.06–93.08]). Conclusions Approximately 40% of the elderly patients suffered from postoperative delirium in major leg amputation. Identifying those with risk factors for postoperative delirium and intervening at the early stage will be of great benefit in major leg amputations for the elderly population.

Abstract Tinnitus is related to serious comorbidities such as suicidal ideation and attempts. Body mass index (BMI) is associated with auditory symptoms including hearing loss. The aim of this nationwide, population-based, cross-sectional study was to evaluate the relationship between mental health, body mass index and tinnitus in a Korean premenopausal female population. This study analyzed data from the Korea National Health and Nutrition Examination Surveys in 2010–2012. Data were collected from 4628 19 years or older, premenopausal women. After adjustments, underweight premenopausal women exhibited a higher odds ratio for tinnitus (odd ratio = 1.54; 95% confidence interval = 1.14–2.08) compared with women of normal weight. Moderate and severe tinnitus was highly prevalent in underweight as well as extremely obese women. The prevalence of perceived stress, melancholy, and suicide ideation was significantly higher in women with tinnitus. The prevalence of perceived stress and suicide ideation was significantly higher in underweight women with tinnitus, but that of melancholy was significantly lower. This study demonstrated that underweight premenopausal Korean women had a higher risk of tinnitus, which has grown in importance as a public health issue. Women with tinnitus experience perceived stress and suicide ideation more frequently, but melancholy less frequently than women without.

The sharing of international academic accomplishment and friendship is important; furthermore, to better understand and anticipate the future, we should look back and remember where we started. Regarding ASIA SPINE, the authors aimed to record how the pioneers of Asian spinal surgery started this spine meeting series more than 20 years ago and that later developed into the present state of the conference. The authors will also explore the possible future of this conference. In June 1996, when Professor Hiroshi Nakagawa organized the 11th Annual Meeting of the Japanese Society of Spinal Surgery, spinal neurosurgeons from Korea and Japan including Professor Young Soo Kim, Professor Jung Keun Suh, and Professor Nakagawa discussed the establishment of a multinational conference on spinal surgery via a partnership between the 2 countries. Finally, from September 18 to 20, 1997, the First Biennial Meeting of the Japan-Korea Conference on Spinal Surgery was held in Nagoya, Japan, with Professor Hiroshi Nakagawa as the first organizing President. From then, a biennial meeting was held every other year in Korea or Japan until 2009. In September 2010, the next generation of spinal neurosurgeons decided to organize the first meeting of ASIA SPINE in Incheon, Korea, in order to represent all Asian spine specialists. This meeting has been since held annually around the region including in Taiwan. Remembering the pioneers in the field of spinal surgery is invaluable and extremely important. The authors hope that interest in ASIA SPINE will further expand to other nations in Asia who have advanced philosophies and refined technologies. We wish ASIA SPINE continued success and the ability to promote prolonged international friendship among the Asian countries.

Objective: To investigate the fungistatic activity and synergistic effects of natural products and their constituents, including traditional oriental medicines (TOMs). Methods: Fungistatic activities of TOMs prepared by hot-water (115 °C) or ethanol (70%; 40 °C) extraction were determined by their minimum inhibitory concentration. To assess possible synergistic effects, minimum inhibitory concentrations of various combinations were evaluated. Results: By evaluating antifungal susceptibility of Trichophyton rubrum, which is a major causative fungus for several types of dermatophytosis, we confirmed that ethanol extracts were more active than hot-water extracts in 25 of the 36 TOMs, suggesting that the constituents with high hydrophobicity tend to contribute significantly to fungistatic activity. We selected four TOMs with high fungistatic activity, including Aucklandiae radix, Gentianae macrophyllae radix, Scutellariae radix, and Galla rhois, and their synergistic effects were investigated through the combination studies between TOMs or TOM-conventional drug terbinafine. In combinations between four TOMs, partial synergistic effects were observed in Aucklandiae radix–Galla rhois and Gentianae macrophyllae radix–Galla rhois combinations, as supported by the lowest fractional inhibitory concentration index value of 0.66 for both combinations. Furthermore, Galla rhois showed the strongest synergistic effect on growth inhibition of Trichophyton rubrum with a fractional inhibitory concentration index value of 0.50 in combination with terbinafine. Conclusions: Our findings indicate that the combination of TOMs and TOM-terbinafine may be effective on treatment for chronic and recurrent dermatophytosis by improving fungistatic activity and led to decrease systemic toxicity in clinical practice.

HSV-1 is a neurotropic virus that replicates lytically during acute infection and establishes latency in peripheral neurons. Currently, the clinically approved compounds for the prevention of HSV-1 infection include acyclovir and penciclovir; however, long-term use of the drug is associated with serious side effects, and drug-resistant strains often appear. Therefore, it is important to find a safe and novel antiviral agent for HSV-1 infection. Quercus acuta Thunb. (Fagaceae) (QA) is widely distributed as an ornamental and dietary plant in Korea, Taiwan, China, and Japan. Thus far, the effects of QA extract and its active ingredients are known to have antioxidant, antibacterial, and anti-inflammatory activity, but studies of possible antiviral effects have not been reported. We studied the antiviral effects and molecular mechanism of QA after HSV-1 infection at the cellular level. We confirmed that QA suppresses ROS expression after HSV-1 infection and also suppresses inflammatory cytokine expression through inhibition of NF-кB activity. In addition, we found that QA increases the phosphorylation activity of IRF3 through induction of TBK1 activity during HSV-1 infection. QA exhibits an antiviral effect, and we confirmed through UPLC-DAD-mass spectrometer (MS)/MS analysis that it contains five main components: catechin, chlorogenic acid, fraxin, isoquercitrin, and taxifolin. Of these, isoquercitrin was confirmed to exhibit an antiviral effect on SK-N-SH cells through ICP27 inhibition. Overall, our results suggest that QA is a novel inhibitor with antiviral effects against HSV-1 infection and may be used specifically to prevent and treat of herpes simplex virus encephalitis infection.

Purpose: The presence of a flow-related signal in the normal dural sinus time of flight magnetic resonance angiography (TOF MRA) is common. This study aimed to identify changes in signal intensity in the dural sinus caused by changes in patient position. Materials and Methods: The researchers performed an elevation TOF MRA of the cerebral region in 52 patients, who showed abnormal flow-related signals in the dural sinuses on supine position. Flow-related signal intensity in the dural sinuses was then analyzed. Results: Flow-related signals were seen in 114 sites (52 patients), specifically in the internal jugular vein (IJV), sigmoid sinus (SS), inferior petrosal sinus (IPS), and cavernous sinus (CS) in 29 sites, 33 sites, 32 sites, and 20 sites, respectively. After head elevation, flow-related signal changes were then observed in the IJV, SS, IPS, and CS in 107 sites (107/114, 93.9%). There was loss of signal (62/114, 54.4%), or decrease (39/114, 34.2%), increase (6/114, 5.3%), or no change (7/114, 6.1%) in the signal intensity, and flow related signals were more frequent on the left than on the right. Conclusion: Flow-related signals in the dural sinuses on TOF MRA were decreased or disappeared by head elevation in 88.6% of the sites. Head elevation may help distinguish between pathologic and physiologic states.

Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulonephritis characterized by diffuse deposits of IgM in the glomerular mesangium. However, its renal prognosis remains unknown. We compared renal outcomes of IgMN patients with those of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or mesangial proliferative glomerulonephritis (MsPGN) from a prospective observational cohort, with 1791 patients undergoing native kidney biopsy in eight hospitals affiliated with The Catholic University of Korea between December 2014 and October 2020. IgMN had more mesangial proliferation and matrix expansion than MsPGN and more tubular atrophy and interstitial fibrosis than MCD. IgMN patients had decreased eGFR than MCD patients in the earlier follow-up. However, there was no significant difference in urine protein or eGFR among all patients at the last follow-up. When IgMN was divided into three subtypes, patients with FSGS-like IgMN tended to have lower eGFR than those with MCD-like or MsPGN-like IgMN but higher proteinuria than MsPGN-like IgMN without showing a significant difference. The presence of hypertension at the time of kidney biopsy predicted ≥20% decline of eGFR over two years in IgMN patients. Our data indicate that IgMN would have a clinical course and renal prognosis similar to MCD, FSGS, and MsPGN.

IgA nephropathy (IgAN) is a globally well-known primary glomerular nephropathy. Hypertriglyceridemia (HTG) is one factor contributing to atherosclerosis and is a common complication of renal failure. HTG is a significant risk factor for decreased renal function in patients with IgAN. We evaluated the association of HTG with the histopathological features of IgAN patients. A total of 480 patients diagnosed with IgAN via kidney biopsy from eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea were included in the final cohort. Pathological features were evaluated by eight expert pathologists with hospital consensus. HTG was defined as a serum triglyceride (TG) level of ≥150 mg/dL. In the study population analysis, the HTG group was older, with more males; higher body mass index (BMI), low-density lipoprotein cholesterol (LDL-C) and spot urine protein ratio; and lower estimated glomerular filtration rate (eGFR). In the lipid profile analysis, eGFR was negatively correlated with TGs/ high-density lipoprotein cholesterol (HDL) and triglyceride-glucose index (TyG). Proteinuria positively correlated with TGs/HDL, non-HDL/HDL, LDL/HDL, TyG, TGs and LDL. The percentages of global sclerosis (GS), segmental sclerosis (SS) and capsular adhesion (CA), and the scores for mesangial matrix expansion (MME) and mesangial cell proliferation (MCP), were more elevated in the HTG group compared to the normal TG group. Multivariable linear regression analysis showed that the percentages of global sclerosis, segmental sclerosis and capsular adhesion, as well as the scores for mesangial matrix expansion and mesangial cell proliferation, were positively associated with TG level. In binary logistic regression, the HTG group showed a higher risk for global sclerosis and segmental sclerosis. In conclusion, HTG is a significant risk factor for glomerulosclerosis in IgAN.

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the development of vaccines, the emergence of SARS-CoV-2 variants and the absence of effective therapeutics demand the continual investigation of COVID-19. Natural products containing active ingredients may be good therapeutic candidates. Here, we investigated the effectiveness of geraniin, the main ingredient in medical plants Elaeocarpus sylvestris var. ellipticus and Nephelium lappaceum, for treating COVID-19. The SARS-CoV-2 spike protein binds to the human angiotensin-converting enzyme 2 (hACE2) receptor to initiate virus entry into cells; viral entry may be an important target of COVID-19 therapeutics. Geraniin was found to effectively block the binding between the SARS-CoV-2 spike protein and hACE2 receptor in competitive enzyme-linked immunosorbent assay, suggesting that geraniin might inhibit the entry of SARS-CoV-2 into human epithelial cells. Geraniin also demonstrated a high affinity to both proteins despite a relatively lower equilibrium dissociation constant (KD) for the spike protein (0.63 μM) than hACE2 receptor (1.12 μM), according to biolayer interferometry-based analysis. In silico analysis indicated geraniin’s interaction with the residues functionally important in the binding between the two proteins. Thus, geraniin is a promising therapeutic agent for COVID-19 by blocking SARS-CoV-2’s entry into human cells.

Hyperuricemia is a significant risk factor for cardiovascular morbidity and chronic kidney disease progression. IgA nephropathy (IgAN) is a well-known primary glomerular nephropathy. Hyperuricemia is associated with a poor prognosis in IgAN patients. We evaluated the association of hyperuricemia with the histopathological severity of IgAN in male and female patients; 658 patients diagnosed with IgAN via kidney biopsy were initially included. Baseline patient data were collected by eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea. Pathological features were independently evaluated by eight expert pathologists working in the hospitals, and the consensus was reached. Of the initial 658 patients, 517 were finally included (253 males and 264 females). Hyperuricemia was defined as a serum uric acid (UA) level >7.0 mg/dL for males and >5.6 mg/dL for females; 108 (42.7%) males and 95 (35.9%) females exhibited hyperuricemia. Compared to the patients with normal UA levels, the global glomerulosclerosis, segmental sclerosis, mesangial matrix expansion (MME), endocapillary proliferation (ECP), interstitial fibrosis (IF), and tubular atrophy (TA) scores were higher in hyperuricemic males and females. In multivariable linear regression, the serum UA level correlated significantly with the MME, ECP, IF, and TA scores of female IgAN patients only.

The 2-stage methods of the total auricular reconstruction developed by Dr. Nagata have been widely used. In the second stage of ear reconstruction, the implanted auricle is separated from the underlying bed, and its posterior surface is covered with a skin graft or a flap. Many surgeons have used various projection blocks, such as banked cartilage or alloplastic materials, to provide the constructed auricle with adequate projection. Banked costal cartilage is most commonly used as a projection block, but it may not be possible to obtain banked cartilage in sufficient volume to ensure an acceptable projection. Previously, in this procedure, the author used a new fabricated cartilage block harvested from the fourth and fifth costal cartilages. Although this material is stable and yields acceptable results, an invasive and time-consuming procedure is necessary to obtain it. Therefore, the author considered the use of a Medpor (a high-density porous polyethylene, Stryker, USA) projection block as an alternative to the cartilage. Between January 2012 and May 2015, the author performed the second-stage operation by using a Medpor block in 51 patients. The follow-up period ranged from 1 year to 4 years. The use of a Medpor block for projection in the second stage is time-saving and less invasive. Delayed healing of the wound was noted in 2 cases, in which a deep temporal fascial flap, instead of a temporoparietal fascial flap, had been used for the coverage of the exposed framework. A hypertrophic scar was noted on the posteroinferior surface of the reconstructed ear in 1 case. However, no major complications such as infection or exposure occurred. The constructed ears showed a firm and stable projection.

Abstract We developed an interdigitated microelectrode (IME) sensor system for blood-based Alzheimer’s disease (AD) diagnosis based on impedimetric detection of amyloid-β (Aβ) protein, which is a representative candidate biomarker for AD. The IME sensing device was fabricated using a surface micromachining process. For highly sensitive detection of several tens to hundreds of picogram/mL of Aβ in blood, medium change from plasma to PBS buffer was utilized with signal cancellation and amplification processing (SCAP) system. The system demonstrated approximately 100-folds higher sensitivity according to the concentrations. A robust antibody-immobilization process was used for stability during medium change. Selectivity of the reaction due to the affinity of Aβ to the antibody and the sensitivity according to the concentration of Aβ were also demonstrated. Considering these basic characteristics of the IME sensor system, the medium change was optimized in relation to the absolute value of impedance change and differentiated impedance changes for real plasma based Aβ detection. Finally, the detection of Aβ levels in transgenic and wild-type mouse plasma samples was accomplished with the designed sensor system and the medium-changing method. The results confirmed the potential of this system to discriminate between patients and healthy controls, which would enable blood-based AD diagnosis.

To study the control of postharvest decay caused by Colletotrichum gloeosporioides and Penicillium expansum, gamma irradiation alone or in combination with fumigation was evaluated to extend the shelf life of apples in South Korea. An irradiation dose of 2.0 kGy resulted in the maximum inhibition of C. gloeosporioides and P. expansum spore germination. The gamma irradiation dose required to reduce the spore germination by 90% was 0.22 and 0.35 kGy for C. gloeosporioides and P. expansum, respectively. Microscopic observations revealed that when the fungal spores were treated with gamma irradiation (4.0 kGy), conidial germination was stopped completely resulting in no germ tube formation in C. gloeosporioides. Treatment with the eco-friendly fumigant ethanedinitrile had a greater antifungal activity against C. gloeosporioides and P. expansum in comparison with the non-treated control under in vitro conditions. The in vitro antifungal effects of the gamma irradiation and fumigation treatments allowed us to further study the effects of the combined treatments to control postharvest decay on stored apples. Interestingly, when apples were treated with gamma irradiation in combined with fumigation, disease inhibition increased more at lower (< 0.4 kGy) than at higher doses of irradiation, suggesting that combined treatments reduced the necessary irradiation dose in phytosanitary irradiation processing under storage conditions.

Background: This study aims to describe the characterization of Paenibacillus polymyxa GBR-1 (GBR-1) with respect to its positive and negative effects on plants. Methods: The morphological characteristics of GBR-1 were identified with microscopy, and subjected to Biolog analysis for identification. Bacterial population and media optimization were determined by a growth curve. The potential for GBR-1 as a growth promoting agent, to have antagonistic activity, and to have hydrolytic activity at different temperatures was assessed. The coinoculation of GBR-1 with other microorganisms and its pathogenicity on various stored plants, including ginseng, were assessed. Results: Colony morphology, endospore-bearing cells, and cell division of GBR-1 were identified by microscopy; identification was performed by utilizing the Biolog system, gas chromatography of fatty acid methyl esters (GC-FAME). GBR-1 showed the strongest antagonistic activity against fungal and bacterial pathogens. GBR-1 cell numbers were relatively higher when the cells were cultured in brain heart infusion (BHI) medium when compared with other media. Furthermore, the starch-hydrolytic activity was influenced by GBR-1 at higher temperature compared to low temperatures. GBR-1 was pathogenic to some of the storage plants. Coinoculation of GBR-1 with other pathogens causes differences in rotting on ginseng roots. A significant growth promotion was observed in tobacco seedlings treated with GBR-1 suspensions under in vitro conditions, suggesting that its volatile organic compounds (VOCs) might play a role in growth promotion. Conclusion: The results of this study indicate that GBR-1 has both positive and negative effects on ginseng root and other stored plants as a potential biocontrol agent and eliciting in vitro growth promotion.