Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOPinduced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects.

Background: To date, various genotypes of infectious bronchitis virus (IBV) have cocirculated and in Korea, GI-15 and GI-19 lineages were prevailing. The spike protein, particularly S1 subunit, is responsible for receptor binding, contains hypervariable regions and is also responsible for the emerging of novel variants. Objective: This study aims to investigate the putative major amino acid substitutions for the variants in GI-19. Methods: The S1 sequence data of IBV isolated from 1986 to 2021 in Korea (n = 188) were analyzed. Sequence alignments were carried out using Multiple alignment using Fast Fourier Transform of Geneious prime. The phylogenetic tree was generated using MEGA-11 (ver.11.0.10) and Bayesian analysis was performed by BEAST v1.10.4. Selective pressure was analyzed via online server Datamonkey. Highlights and visualization of putative critical amino acid were conducted by using PyMol software (version 2.3). Results: Most (93.5%) belonged to the GI-19 lineage in Korea, and the GI-19 lineage was further divided into seven subgroups: KM91-like (Clade A and B), K40/09-like, QX-like (I-IV).Positive selection was identified at nine and six residues in S1 for KM91-like and QX-like IBVs, respectively. In addition, several positive selection sites of S1-NTD were indicated to have mutations at common locations even when new clades were generated. They were all located on the lateral surface of the quaternary structure of the S1 subunits in close proximity to the receptor-binding motif (RBM), putative RBM motif and neutralizing antigenic sites in S1. Conclusions Our results suggest RBM surrounding sites in the S1 subunit of IBV are highly susceptible to mutation by selective pressure during evolution.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Objective: : ABM/P-15 (anorganic bone matrix/15-amino acid peptide fragment) is a commercially available synthetically manufactured P-15 collagen peptide fragment, that is adsorbed on ABM. This study was done to investigate the efficacy of ABM/ P-15 in achieving fusion in the lumbar spine and comparing it with that of recombinant bone morphogenic protein-2 (rhBMP-2) and demineralized bone matrix (DBM). Methods: : A retrospective observational study of prospectively collected data of 140 patients who underwent lumbar spinal fusion surgeries in a single specialty spine hospital between 2016 and 2020, with a minimum 6-month follow-up was conducted. Based on the material used for the augmentation of the bone graft at the fusion site, the patients were divided into three categories namely ABM/P-15, rhBMP-2, and DBM group. Results: : ABM/P-15, rhBMP-2, and DBM were used in 46, 44, and 50 patients, respectively. Patient characteristics like age, gender, bone mineral density, smoking history, and presence of diabetes mellitus were comparable amongst the three groups. Average follow-up was 16.0±5.2, 17.9±9.8, and 26.2±14.9 months, respectively in ABM/P-15, rhBMP-2, and DBM groups. The fusion was achieved in 97.9%, 93.2%, and 98% patients while the average time-to-union was 4.05±2.01, 10±4.28, and 9.44±3.49 months (p<0.001), respectively for ABM/P-15, rhBMP-2, and DBM groups. The average pre-operative Visual analogue scale score was 6.93±2.42, 7.14±1.97, 7.01±2.14 (p=0.900) for ABM/P-15, rhBMP-2 and DBM groups, respectively, which reduced to 1.02±0.80, 1.21±0.96, and 0.54±0.70 (p=0.112), respectively at the last follow up. Pre-operative Oswestry disability index scores were 52.7±18.02, 55.4±16.8, and 53.56±19.6 (p=0.751) in ABM/P-15, rhBMP-2, and DBM groups, which post-operatively reduced to 33.77±15.52, 39.42±16.47, and 38.3±15.89 (p=0.412) and further to 15.74±8.3, 17.41±10.45, and 16.76±9.81 (p=0.603), respectively at the last follow-up. Conclusion : ABM/P-15 appears to achieve union significantly earlier than rhBMP-2 and DBM in lumbar spinal fusion cases while maintaining a comparable clinical and complication profile.

Background: This study aimed to investigate the association between e-cigarette (EC) use and development of acute severe pneumonia in the Korean population using a national database. Methods: We conducted a retrospective analysis using linkage of data between the Korean National Health and Nutrition Examination Survey (KNHANES) and the National Health Insurance Service (NHIS) administrative claims database. The primary endpoint of this study was development of severe pneumonia requiring hospital admission according to EC use during the study period. The secondary endpoints were in-hospital mortality, intensive care unit (ICU) admission, ventilator care, and days of hospital stay. Results: The final analysis included 28,950 individuals, of which 578 (2.0%) were EC users.EC users were younger and more often male than non-EC users. The EC users showed higher level of education and household income and had fewer comorbidities. Severe pneumonia was noted in 37 of 28,372 non-EC users (0.13%), but there were no occurrences of severe pneumonia in EC users. The incidence of pneumonia occurrence was not different between the two groups (P = 1.000). Conclusions Since e-cigarette or vaping use-associated lung injury (EVALI) is most likely included in acute severe pneumonia occurring within 3 months of EC use, it is considered that there might be no EVALI patients in Korea during the investigation period. A large-scale, prospective study is necessary to evaluate the association between EC use and acute lung injury.

Excessive intake of sodium caused by high salt diet promotes the expression of inflammatory cytokines and differentiation of helper T cells resulting in inflammatory responses. High-glucose diet also contributes to the pathogenesis of periodontitis by inducing changes in the oral microbiome and reducing salivation. However, the effect of a high-salt and glucose diet (HSGD) on the prognosis of periodontitis remains unclear. In this study, a rat modelof experimental periodontitis was established by periodic insertion of absorbable sutures containing Porphyromonas gingivalis and Fusobacterium nucleatum strains into the right gingival sulcus to analyze the effect of HSGD on the incidence and progression of periodontitis. The alveolar bone heights (ABH) was measured with microcomputed tomography imaging of the HSGD- and general diet (GD)-treated groups. The right ABH was significantly decreased compared to the left in both groups at 4 weeks after induction of inflammation; however, no significant difference was noted between the groups. Notably, the ABH in the HSGD-treated group was significantly decreased at 8 weeks after induction of inflammation, whereas in the GD-treated group, an increase in the ABH was observed; a significant difference of the ABH was noted between the two groups (p < 0.05). At 12 weeks, recovery of the alveolar bone was observed in both groups, with no significant differences in ABH between the two groups. These findings indicate that the intake of excessive sodium attenuates the recovery rate of the alveolar bone even after the local infectant isremoved. In addition, this study demonstrates the use of HSGD in establishing a new animal model of periodontitis.

PURPOSE: An oral cholera vaccine (OCV), Euvichol, with thimerosal (TM) as preservative, was prequalified by the World Health Organization (WHO) in 2015. In recent years, public health services and regulatory bodies recommended to eliminate TM in vaccines due to theoretical safety concerns. In this study, we examined whether TM-free Euvichol induces comparable immunogenicity to its TM-containing formulation in animal model. MATERIALS AND METHODS: To evaluate and compare the immunogenicity of the two variations of OCV, mice were immunized with TM-free or TM-containing Euvichol twice at 2-week interval by intranasal or oral route. One week after the last immunization, mice were challenged with Vibrio cholerae O1 and daily monitored to examine the protective immunity against cholera infection. In addition, serum samples were obtained from mice to measure vibriocidal activity and vaccine-specific IgG, IgM, and IgA antibodies using vibriocidal assay and enzyme-linked immunosorbent assay, respectively. RESULTS: No significant difference in immunogenicity, including vibriocidal activity and vaccine-specific IgG, IgM, and IgA in serum, was observed between mice groups administered with TM-free and -containing Euvichol, regardless of immunization route. However, intranasally immunized mice elicited higher levels of serum antibodies than those immunized via oral route. Moreover, intranasal immunization completely protected mice against V. cholerae challenge but not oral immunization. There was no significant difference in protection between two Euvichol variations. CONCLUSION: These results suggested that TM-free Euvichol could provide comparable immunogenicity to the WHO prequalified Euvichol containing TM as it was later confirmed in a clinical study. The pulmonary mouse cholera model can be considered useful to examine in vivo the potency of OCVs.
Animals* ; Antibodies ; Cholera Vaccines ; Cholera* ; Clinical Study ; Enzyme-Linked Immunosorbent Assay ; Immunization ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Mice ; Models, Animal* ; Public Health ; Thimerosal ; Vaccines ; Vibrio cholerae O1 ; World Health Organization

Exosomes are Nano-sized lipid vesicles secreted from mammalian cells containing diverse cellular materials such as proteins, lipids, and nucleotides. Multiple lines of evidence indicate that in saliva, exosomes and their contents such as microRNAs (miRNAs) mediate numerous cellular responses upon delivery to recipient cells. The objective of this study was to characterize the different expression profile of exosomal miRNAs in saliva samples, periodically isolated from a single periodontitis patient. Unstimulated saliva was collected from a single patient over time periods for managing periodontitis. MicroRNAs extracted from each phase were investigated for the expression of exosomal miRNAs. Salivary exosomal miRNAs were analyzed using Affymetrix miRNA arrays and prediction of target genes and pathways for its different expression performed using DIANA-mirPath, a web-based, computational tool. Following the delivery of miRNA mimics (hsa-miR-4487, -4532, and -7108-5p) into human gingival fibroblasts, the expression of pro-inflammatory cytokines and activation of the MAPK pathway were evaluated through RT-PCR and western blotting. In each phase, 13 and 43 miRNAs were found to be differently expressed (|FC| ≥ 2). Among these, hsa-miR-4487 (|FC|=9.292005) and hasmiR-4532 (|FC|=18.322697) were highly up-regulated in the clinically severe phase, whereas hsa-miR-7108-5p (|FC|= 12.20601) was strongly up-regulated in the clinically mild phase. In addition, the overexpression of miRNA mimics in human gingival fibroblasts resulted in a significant induction of IL-6 mRNA expression and p38 phosphorylation. The findings of this study established alterations in salivary exosomal miRNAs which are dependent on the severity of periodontitis and may act as potential candidates for the treatment of oral inflammatory diseases.
Blotting, Western ; Cytokines ; Exosomes ; Fibroblasts ; Humans ; Interleukin-6 ; MicroRNAs ; Nucleotides ; Periodontitis ; Phosphorylation ; Pilot Projects ; RNA, Messenger ; Saliva

PURPOSE: Perinatal hypoxic-ischemic (HI) brain injury remains a common cause of chronic handicapping conditions of cerebral palsy, mental retardation, learning disability, and epilepsy. HI brain injury induces cell death via either necrosis or apoptosis. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family. It plays key roles in survival, differentiation, and maintenance of neurons. This study was to investigate the neuroprotective effects of BDNF via the mechanisms of anti-apoptosis in HI brain injury by using cortical astrocyte and neuronal cell culture. METHODS: Cortical astrocytes culture of 1-day-old Sprague-Dawley (SD) rat pups and embryonic cortical neuronal cell culture of SD rats at 14-day gestation were done. The Normoxia group was prepared in 5% CO2 incubators and the Hypoxia group and Hypoxia+BDNF group (after treatment with BDNF for 24 hours) were placed in 1% O2 incubators (94% N2, 5% CO2) for 6 or 18 hours. The expression of Bcl-2 and Bax were assessed by real-time PCR and western blot. The caspase-3 activation was evaluated by caspase activity assay kit. RESULTS: In astrocyte and neuronal cell, the expressions of Bcl-2 in the hypoxia groups were reduced compared to the normoxia groups, whereas, those in the Hypoxia+BDNF groups were increased compared to the hypoxia groups. However, the expressions of Bax and caspase-3 and the ratio of Bax/Bcl-2 were revealed reversely. In astrocyte, Hypoxia group for 6 hours was not significantly altered in Bcl-2, Bax expressions. CONCLUSION: BDNF neuroprotective effects on HI brain injury in neonatal rats may occur via anti-apoptotic mechanism.
Animals ; Anoxia ; Apoptosis ; Astrocytes ; Blotting, Western ; Brain Injuries ; Brain* ; Brain-Derived Neurotrophic Factor* ; Caspase 3 ; Cell Culture Techniques ; Cell Death ; Cerebral Palsy ; Epilepsy ; Humans ; Incubators ; Intellectual Disability ; Learning Disorders ; Necrosis ; Neurons ; Neuroprotective Agents ; Pregnancy ; Rats* ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction

BACKGROUND: It is important to ensure that patients are normothermic during surgery. In total knee arthroplasty, the pneumatic tourniquet affects body temperature. We compared the ability of two warming devices to preserve core temperature in patients using a lower limb tourniquet under general anesthesia. METHODS: We included 132 patients with American Society of Anesthesiologists physical status I-II who were scheduled to undergo total knee arthroplasty. The patients were randomly divided into four groups (n = 33): group 1, without any heating method; group 2, with fluid warming; group 3, with forced-air warming; and group 4, with a combination of the two heating methods. After the induction of anesthesia, the esophageal and urinary bladder temperatures were monitored and recorded every 5 min before tourniquet deflation and every 1 min after tourniquet deflation. RESULTS: Before tourniquet deflation, compared with group 1, the odds ratios of groups 3 and 4 were less than 1. After tourniquet deflation, compared with group 1, the odds ratios of all groups using warming devices were less than 1. In particular, group 4 showed the largest hypothermia-preventive effect among the four groups. There was a significant correlation between esophageal temperature and bladder temperature before and after tourniquet deflation. CONCLUSIONS: After tourniquet deflation, a combination of a fluid warmer and forced-air warmer is the most effective method to prevent hypothermia, although either a fluid warmer or forced-air warmer alone could help to prevent hypothermia. Urinary bladder temperature changes correlate well with esophageal temperature changes throughout this operation.
Anesthesia ; Anesthesia, General ; Arthroplasty* ; Arthroplasty, Replacement, Knee ; Body Temperature ; Heating ; Hot Temperature ; Humans ; Hypothermia ; Knee* ; Lower Extremity ; Methods* ; Odds Ratio ; Tourniquets* ; Urinary Bladder