Natural Phytochemical and Visible Light at Different Wavelengths Show Synergistic Antibacterial Activity against Staphylococcus aureus.

As the risk of antibiotic-resistant bacteria increases, interest in non-antibiotic treatment is also increasing. Among the methods used in non-antibiotic therapy, natural antibiotics such as essential oils have disadvantages such as low efficiency. In the case of phototherapy, the light used for antibacterial activities has low penetration into the human body because of its short wavelength, making it of low medical utility. To solve this problem, this study aimed to determine conditions for enhancing the antibacterial activity of natural phytochemicals and visible light. Four natural phytochemical extracts that showed high antibacterial properties in previous studies were analyzed. Synergistic effects on antibacterial activity and cytotoxicity were determined when natural phytochemical extracts and visible light were simultaneously used. As a result, it was confirmed that the antibacterial activity increased by four times when Sanguisorba officinalis L. was irradiated with 465 nm for 10 min and 520 nm for 40 min, and Uncaria gambir Roxb. was irradiated with 465 nm for 10 min and 520 nm for 60 min compared to when Sanguisorba officinalis L. and Uncaria gambir Roxb. were used alone. The synergistic effect on antibacterial activity was independent of the absorption peak of the natural phytochemical extracts. In addition, in the case of natural phytochemical extracts with improved antibacterial activity, it was confirmed that the improvement of antibacterial activity was increased in inverse proportion to the light irradiation wavelength and in proportion to the light irradiation time. The antibacterial activity was enhanced regardless of antibiotic resistance. In the case of cytotoxicity, it was confirmed that there was no toxicity to A549 cells when treated with 465 nm, the shortest wavelength among the natural phytochemical extracts. These results show how to replace blue light, which has been underutilized due to its low transmittance and cytotoxicity. They also demonstrate the high medical potential of using natural phytochemical and visible light as a combination therapy.

In Vitro Synergistic Inhibitory Effects of Plant Extract Combinations on Bacterial Growth of Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common pathogens of healthcare-associated infections. Medicinal plants have long been used in the traditional treatment of diseases or syndromes worldwide. Combined use of plant extracts could improve the effectiveness of pharmacological action by obtaining synergism, acting on multiple targets simultaneously, reducing the doses of individual components, and minimizing side effects. We aimed to investigate the synergistic inhibitory effects of selected medicinal plants (Caesalpinia sappan L. (CS), Glycyrrhiza uralensis Fisch. (GU), Sanguisorba officinalis L. (SO), and Uncaria gambir Roxb. (UG)) on the bacterial growth of MRSA and its clinical isolates. SO and UG extracts generated the best synergistic interaction as adjudged by checkerboard synergy assays. MICs of the individual extracts decreased 4-fold from 250 to 62.5 µg/mL, respectively. The SO + UG combination was further evaluated for its effects on bacterial growth inhibition, minimum bactericidal/inhibitory concentration (MBC/MIC) ratio, and time-kill kinetics. The results indicate that the SO + UG combination synergistically inhibited the bacterial growth of MRSA strains with bactericidal effects. SO + UG combination also exhibited more potent effects against clinical isolates. In multistep resistance selection experiments, both standard and isolates of MRSA showed no resistance to the SO + UG combination even after repeated exposure over fourteen passages. Our data suggest that using plant extract combinations could be a potential strategy to treat MRSA infections.

Comparing the Phylogenetic Distribution of Multilocus Sequence Typing, Staphylococcal Protein A, and Staphylococcal Cassette Chromosome Mec Types in Methicillin-Resistant Staphylococcus Aureus (MRSA) in Korea from 1994 to 2020.

Staphylococcus aureus (S. aureus) bacteremia is one of the most frequent and severe bacterial infections worldwide. Methicillin-resistant Staphylococcus aureus (MRSA) is a serious human pathogen that can cause a wide variety of infections. Comparative genetic analyses have shown that despite the existence of a vast number of genotypes, genotypes are restricted to certain geographical locations. By comparing multilocus sequence typing (MLST) and SCCmec types from 1994 to 2020, the present study intended to discover which genotype genes were related to MRSA infections. MLST, Staphylococcus aureus protein A (spa), and SCCmec typings were performed to determine their relationship during those years. Results revealed that MRSA isolates in the Republic of Korea were distributed among all major staphylococcal cassette chromosome mec (SCCmec) types. The majority of SCCmec isolates belonged to SCCmec type II and type IV. The majority of MLST had the sequence type (ST) 72, 239, 8, or 188. By contrast, minorities belonged to ST22 (SCCmec IV), ST772 (SCCmec V), and ST672 (SCCmec V) genotypes. The SCCmec type was determined for various types. The spa type was dispersed, seemingly regardless of its multidrug resistance property. The MLST type was found to be similar to the existing typical type. These results showed some correlations between resistance characteristics and types according to the characteristics of the MLST types distributed, compared to previous papers. Reports on genotype distribution of MLST and SCCmec types in MRSA are rare. These results show a clear distribution of MLST and SCCmec types of MRSA from 1994 to 2020 in the Republic of Korea.

Inhibitory Effects of Selected Medicinal Plants on Bacterial Growth of Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious threat to global public health due to its capacity of tolerate conventional antibiotics. Medicinal plants are traditionally used to treat infectious diseases caused by bacterial pathogens. In the present study, 16 medicinal plants were screened for antibacterial activities to preselect more effective species. Ethanol extracts of selected medicinal plants (Caesalpinia sappan L., Glycyrrhiza uralensis Fisch., Sanguisorba officinalis L., and Uncaria gambir Roxb) were partitioned successively with different solvents (n-hexane, chloroform, ethyl acetate, 1-butanol, and water). Disc diffusion assay and broth microdilution were performed to evaluate the antibacterial activities of plant extracts and fractions against Staphylococcus aureus strains. Furthermore, the cytotoxicity of the extracts and fractions was determined against the human hepatoma (HepG2) and human lung carcinoma (A549) cell lines using a trypan blue exclusion method. A few extracts and fractions showed significant inhibitory effects on the bacterial growth of all tested strains, including multidrug-resistance (MDR) clinical isolates. The ethyl acetate fraction of C. sappan had the most potent effects with minimum inhibitory/bactericidal concentrations (MIC/MBC) of 31.2/62.5 µg/mL and showed low cytotoxicity with over 90% cell viability in both cells. Our results suggest that medicinal plants have considerable potential as alternatives to conventional antibiotics.

Korean Red Ginseng and Ginsenoside Rg3 Suppress Asian Sand Dust-Induced Epithelial-Mesenchymal Transition in Nasal Epithelial Cells.

Chronic rhinosinusitis (CRS) is characterized by chronic inflammation of the sinonasal mucosa with epithelial dedifferentiation toward the mesenchymal phenotype, known as the epithelial-mesenchymal transition (EMT). Asian sand dust (ASD) can induce nasal mucosal inflammation and cause the development of EMT. Korean red ginseng (KRG) and ginsenoside Rg3 have been used as traditional herbal medicines to treat various diseases. The aim of this study was to investigate their effect on ASD-induced EMT in nasal epithelial cells. Primary nasal epithelial cells were incubated with ASD with or without KRG or Rg3, and the production of transforming growth factor-ß1 (TGF-ß1) and interleukin (IL)-8 was measured. EMT markers were determined by RT-PCR, Western blot analysis, and confocal microscopy, and transcription factor expression by Western blot analysis. The effect on cell migration was evaluated using the wound scratch assay. Results showed ASD-induced TGF-ß1 production, downregulation of E-cadherin, and upregulation of fibronectin in nasal epithelial cells. KRG and Rg3 suppressed TGF-ß1 production (31.7% to 43.1%), upregulated the expression of E-cadherin (26.4% to 88.3% in mRNA), and downregulated that of fibronectin (14.2% to 46.2% in mRNA and 52.3% to 70.2% in protein). In addition, they suppressed the ASD-induced phosphorylation of ERK, p38, and mTOR, as well as inhibiting the ASD-induced migration of nasal epithelial cells (25.2% to 41.5%). The results of this study demonstrate that KRG and Rg3 inhibit ASD-induced EMT by suppressing the activation of ERK, p38, and mTOR signaling pathways in nasal epithelial cells.

Design Guidelines of a Computer-Based Intervention for Computer Vision Syndrome: Focus Group Study and Real-World Deployment.

BACKGROUND: Prolonged time of computer use increases the prevalence of ocular problems, including eye strain, tired eyes, irritation, redness, blurred vision, and double vision, which are collectively referred to as computer vision syndrome (CVS). Approximately 70% of computer users have vision-related problems. For these reasons, properly designed interventions for users with CVS are required. To design an effective screen intervention for preventing or improving CVS, we must understand the effective interfaces of computer-based interventions. OBJECTIVE: In this study, we aimed to explore the interface elements of computer-based interventions for CVS to set design guidelines based on the pros and cons of each interface element. METHODS: We conducted an iterative user study to achieve our research objective. First, we conducted a workshop to evaluate the overall interface elements that were included in previous systems for CVS (n=7). Through the workshop, participants evaluated existing interface elements. Based on the evaluation results, we eliminated the elements that negatively affect intervention outcomes. Second, we designed our prototype system LiquidEye that includes multiple interface options (n=11). Interface options included interface elements that were positively evaluated in the workshop study. Lastly, we deployed LiquidEye in the real world to see how the included elements affected the intervention outcomes. Participants used LiquidEye for 14 days, and during this period, we collected participants' daily logs (n=680). Additionally, we conducted prestudy and poststudy surveys, and poststudy interviews to explore how each interface element affects participation in the system. RESULTS: User data logs collected from the 14 days of deployment were analyzed with multiple regression analysis to explore the interface elements affecting user participation in the intervention (LiquidEye). Statistically significant elements were the instruction page of the eye resting strategy (P=.01), goal setting of the resting period (P=.009), compliment feedback after completing resting (P<.001), a mid-size popup window (P=.02), and CVS symptom-like effects (P=.004). CONCLUSIONS: Based on the study results, we suggested design implications to consider when designing computer-based interventions for CVS. The sophisticated design of the customization interface can make it possible for users to use the system more interactively, which can result in higher engagement in managing eye conditions. There are important technical challenges that still need to be addressed, but given the fact that this study was able to clarify the various factors related to computer-based interventions, the findings are expected to contribute greatly to the research of various computer-based intervention designs in the future.

Interdigitated and Wave-Shaped Electrode-Based Capacitance Sensor for Monitoring Antibiotic Effects.

Label-free and real-time monitoring of the bacterial viability is essential for the accurate and sensitive characterization of the antibiotic effects. In the present study, we investigated the feasibility of the interdigitated and wave-shaped electrode (IWE) for monitoring the effect of tetracycline or kanamycin on Staphylococcus aureus (S. aureus) and methicillin-resistant S.aureus (MRSA). The electrical impedance spectra of the IWE immersed in the culture media for bacterial growth were characterized in a frequency range of 10 Hz to 1 kHz. The capacitance index (CI) (capacitance change relevant with the bacterial viability) was used to monitor the antibiotic effects on the S. aureus and MRSA in comparison to the traditional methods (disk diffusion test and optical density (OD) measurement). The experimental results showed that the percentage of change in CI (PCI) for the antibiotic effect on MRSA was increased by 51.58% and 57.83% in kanamycin and control, respectively. In contrast, the PCI value decreased by 0.25% for tetracycline, decreased by 52.63% and 37.66% in the cases of tetracycline and kanamycin-treated S. aureus, and increased 2.79% in the control, respectively. This study demonstrated the feasibility of the IWE-based capacitance sensor for the label-free and real-time monitoring of the antibiotic effects on S.aureus and MRSA.

Exploring Abnormal Behavior Patterns of Online Users With Emotional Eating Behavior: Topic Modeling Study.

BACKGROUND: Emotional eating (EE) is one of the most significant symptoms of various eating disorders. It has been difficult to collect a large amount of behavioral data on EE; therefore, only partial studies of this symptom have been conducted. To provide adequate support for online social media users with symptoms of EE, we must understand their behavior patterns to design a sophisticated personalized support system (PSS). OBJECTIVE: This study aimed to analyze the behavior patterns of emotional eaters as the first step to designing a personalized intervention system. METHODS: The machine learning (ML) framework and Latent Dirichlet Allocation (LDA) topic modeling tool were used to collect and analyze behavioral data on EE. Data from a subcommunity of Reddit, /r/loseit, were analyzed. This dataset included all posts and feedback from July 2014 to May 2018, comprising 185,950 posts and 3,528,107 comments. In addition, deleted and improperly collected data were eliminated. Stochastic gradient descent-based ML classifier with an accuracy of 90.64% was developed to collect refined behavioral data of online users with EE behaviors. The expert group that labeled the dataset to train the ML classifiers included a medical doctor specializing in EE diagnosis and a nutritionist with profound knowledge of EE behavior. The experts labeled 5126 posts as EE (coded as 1) or others (coded as 0). Finally, the topic modeling process was conducted with LDA. RESULTS: The following 4 macroperspective topics of online EE behaviors were identified through linguistic evidence regarding each topic: addressing feelings, sharing physical changes, sharing and asking for dietary information, and sharing dietary strategies. The 5 main topics of feedback were dietary information, compliments, consolation, automatic bot feedback, and health information. The feedback topic distribution significantly differed depending on the type of EE behavior (overall P<.001). CONCLUSIONS: This study introduces a data-driven approach for analyzing behavior patterns of social website users with EE behaviors. We discovered the possibility of the LDA topic model as an exploratory user study method for abnormal behaviors in medical research. We also investigated the possibilities of ML- and topic modeling-based classifiers to automatically categorize text-based behavioral data, which could be applied to personalized medicine in future research.

Sulforaphane epigenetically enhances neuronal BDNF expression and TrkB signaling pathways.

SCOPE: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. We investigated the effect of sulforaphane, a hydrolysis product of glucoraphanin present in Brassica vegetables, on neuronal BDNF expression and its synaptic signaling pathways. METHODS AND RESULTS: Mouse primary cortical neurons and a triple-transgenic mouse model of Alzheimer's disease (3 × Tg-AD) were used to study the effect of sulforaphane. Sulforaphane enhanced neuronal BDNF expression and increased levels of neuronal and synaptic molecules such as MAP2, synaptophysin, and PSD-95 in primary cortical neurons and 3 × Tg-AD mice. Sulforaphane elevated levels of synaptic TrkB signaling pathway components, including CREB, CaMKII, ERK, and Akt in both primary cortical neurons and 3 × Tg-AD mice. Sulforaphane increased global acetylation of histone 3 (H3) and H4, inhibited HDAC activity, and decreased the level of HDAC2 in primary cortical neurons. Chromatin immunoprecipitation analysis revealed that sulforaphane increased acetylated H3 and H4 at BDNF promoters, suggesting that sulforaphane regulates BDNF expression via HDAC inhibition. CONCLUSION: These findings suggest that sulforaphane has the potential to prevent neuronal disorders such as Alzheimer's disease by epigenetically enhancing neuronal BDNF expression and its TrkB signaling pathways.

Dexamethasone inhibits hypoxia-induced epithelial-mesenchymal transition in colon cancer.

AIM: To elucidate the effects of dexamethasone on hypoxia-induced epithelial-to-mesenchymal transition (EMT) in colon cancer. METHODS: Human colon cancer HCT116 and HT29 cells were exposed to normoxic (21%) and hypoxic (1%) conditions. First, the effect of dexamethasone on cell viability was examined by MTT cell proliferation assay. In order to measure the expression levels of EMT markers (Snail, Slug, Twist, E-cadherin, and integrin αVß6) and hypoxia-related genes [Hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF)] by dexamethasone, quantitative real-time polymerase chain reaction and western blot analysis were performed. Furthermore, the morphological changes of colon cancer cells and the expression pattern of E-cadherin by dexamethasone were detected through immunocytochemistry. Finally, the effects of dexamethasone on the invasiveness and migration of colon cancer cells were elucidated using matrigel invasion, migration, and wound healing migration assays. RESULTS: Under hypoxia, dexamethasone treatment inhibited HIF-1α protein level and its downstream gene, VEGF mRNA level in the colon cancer cell lines, HCT116 and HT29. In addition, the presence of dexamethasone down-regulated the mRNA levels of hypoxia-induced Snail, Slug, and Twist, all transcriptional factors of EMT, as well as hypoxia-induced integrin αVß6 protein level, a well-known EMT marker for colon cancer cells. Furthermore, reduced E-cadherin in hypoxic condition was found to be recoverable by treating with dexamethasone in both colon cancer cell lines. Similarly, under hypoxic conditions, dexamethasone restored the growth pattern and morphological phenotype reminiscent of colon cancer cells grown under normoxic conditions; dexamethasone blocked the migration and invasion of both colorectal cancer cell lines in hypoxia. CONCLUSION: Our study suggested that dexamethasone has inhibitory effects on cell migration and invasion by suppressing EMT of colon cancer cell lines in hypoxic condition.

The effect of Asian sand dust-activated respiratory epithelial cells on activation and migration of eosinophils.

UNLABELLED: CONTEST: Asian sand dust (ASD) contains various chemical and microbiological materials. ASD aggravate the inflammatory response of respiratory epithelial cells and symptoms of asthma. OBJECTIVE: To evaluate the inflammatory effects of ASD on the activation of bronchial epithelial cells and the effect on the activation and migration of eosinophils. MATERIALS AND METHODS: BEAS-2B cells were exposed to three forms of ASD: particles less than 10 µm in diameter (PM), dried sand dust (SD) and sand dust collected from the Gobi Desert (GB). Activation of the epithelial cells was determined using interleukin-6 (IL-6), IL-8, granulocyte macrophage colony-stimulating factor (GM-CSF), regulated on activation normal T expressed and secreted (RANTES), and eotaxin. Eosinophil migration was induced with bronchial epithelial cell conditioned medium. Eosinophils were stimulated with the ASDs and production of superoxide and eosinophil cationic protein was measured. RESULTS: PM and SD enhanced the production of IL-6, IL-8 and RANTES. However, only IL-6 production was significantly increased with GB. Conditioned medium stimulated PM and SD enhanced the migration of eosinophils. PM and SD strongly activated eosinophils. DISCUSSION AND CONCLUSIONS: ASD, which contains smaller particles and air pollutants, might exacerbate the inflammatory process of bronchial tissue and asthmatic symptoms with the production of inflammatory mediators and tissue eosinophilia.

Asian sand dust enhances rhinovirus-induced cytokine secretion and viral replication in human nasal epithelial cells.

CONTEXT: Asian sand dust (ASD) originating in the arid deserts of Mongolia and China causes annual severe air pollution events in the Asia-Pacific area, including Korea, Japan, and China. ASD is thought to impact public health by aggravating or inducing respiratory illness. Among the most common respiratory illnesses is the common cold caused by rhinovirus (RV) infection. To date, however, the impact of ASD on RV infection has not been studied. OBJECTIVE: In this study, we investigated the effect of ASD on RV infection in human nasal epithelial cells. METHODS: Primary human nasal epithelial cells grown at an air-liquid interface were treated with ASD and/or RV. After RV infections were confirmed using semi-nested reverse transcription-polymerase chain reaction (RT-PCR), mRNA expression and protein secretion of the inflammatory cytokines interferon-γ (IFN-γ), interleukin-1ß (IL-1ß),IL-6, and IL-8, indicators of the severity of RV-induced inflammation, were measured by real-time PCR and enzyme-linked immunosorbent assays. Viral titer was also assayed by culturing viruses to compare viral replication between RV-only and ASD-plus-RV groups. RESULTS: ASD significantly increased RV-induced IFN-γ, IL-1ß, IL-6, and IL-8 mRNA levels and protein secretion in primary nasal epithelial cells. In addition, ASD caused a significant increase in RV replication. CONCLUSIONS: Our results suggest that ASD may potentiate common cold symptoms associated with RV infection not only by enhancing IFN-γ, IL-1ß, IL-6, and IL-8 secretion, but also by increasing viral replication.

Polymorphism at the glutathione S-transferase P1 locus in Korean patients with perennial allergic rhinitis.

BACKGROUND: Oxidative stresses, which induce the reactive oxygen species (ROS), can cause airway inflammation. The glutathione S-transferases (GSTs) protect cells against the effects of ROS. GSTP1 polymorphism may have some effect on allergic rhinitis. Therefore, we have compared the effects of GSTP1 polymorphisms on the perennial allergic rhinitis in Koreans. METHODS: Patients with perennial allergies (149 patients) were selected. The control group included 156 healthy people. Genotypes were evaluated via polymerase chain reaction and restriction fragment length polymorphism, using the Alw26I restriction enzyme. RESULTS: There was no significant difference between groups in the proportions of the Ile/Ile (wild type) and Ile/Val (heterozygote) genotypes. However, the Val/Val (mutant type homozygote) was expressed in only one case (0.7%) in the perennial allergic rhinitis group, as compared with 11 cases (7.1%) in the controls (p < 0.05). CONCLUSION: Our results indicate that the Val/Val genetic polymorphism of GSTP1 may exert some protective effects in allergic inflammation.

Tumor-associated carbonic anhydrases are linked to metastases in primary cervical cancer.

PURPOSE: Carbonic anhydrase IX (CA9) has emerged as an important surrogate marker for hypoxia in solid tumors. CA12 shares a role with CA9 in acidification of micromilieu but it is less strictly regulated by hypoxia than CA9. In this study, we investigated expression of CA9 and CA12 mRNA in primary cervical cancer. We also examined whether CA9 expression can be an indicator of reoxygenation of tumor by measuring its mRNA expression during fractionated radiotherapy. METHODS: Tumor tissues were obtained from 59 patients with uterine cervical cancer who underwent radiotherapy, and a second biopsy was taken after patients had received either 10 or 20 Gy of radiation. The follow-up period ranged from 2.4 to 75 months (median=23 months). The ratio of CA9 and beta-actin mRNA expression was determined both pre- and during radiation treatment by RT-PCR. RESULTS: CA9 and CA12 mRNA expression was detected in 62.7 and 88.1% of tumors (i.e. patients), respectively, and co-expression was observed in 61% of patients. Multivariate analysis revealed that CA9 expression was the most significant factor associated with metastasis-free survival (P=0.008, hazard ratio 34.8), whereas CA12 mRNA expression was linked to a lower risk of metastasis (P=0.007, hazard ratio of 0.07). Tumor CA9 expression was not altered following either 10 or 20 Gy of radiotherapy. CONCLUSION: The strong correlation between CA9 expression and metastasis suggests that CA9 expression might be an important indicator for identifying patients who require more aggressive systemic therapy.