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1.
Genome Res ; 34(5): 796-809, 2024 06 25.
Article in English | MEDLINE | ID: mdl-38749656

ABSTRACT

Underrepresented populations are often excluded from genomic studies owing in part to a lack of resources supporting their analyses. The 1000 Genomes Project (1kGP) and Human Genome Diversity Project (HGDP), which have recently been sequenced to high coverage, are valuable genomic resources because of the global diversity they capture and their open data sharing policies. Here, we harmonized a high-quality set of 4094 whole genomes from 80 populations in the HGDP and 1kGP with data from the Genome Aggregation Database (gnomAD) and identified over 153 million high-quality SNVs, indels, and SVs. We performed a detailed ancestry analysis of this cohort, characterizing population structure and patterns of admixture across populations, analyzing site frequency spectra, and measuring variant counts at global and subcontinental levels. We also show substantial added value from this data set compared with the prior versions of the component resources, typically combined via liftOver and variant intersection; for example, we catalog millions of new genetic variants, mostly rare, compared with previous releases. In addition to unrestricted individual-level public release, we provide detailed tutorials for conducting many of the most common quality-control steps and analyses with these data in a scalable cloud-computing environment and publicly release this new phased joint callset for use as a haplotype resource in phasing and imputation pipelines. This jointly called reference panel will serve as a key resource to support research of diverse ancestry populations.


Subject(s)
Databases, Genetic , Genome, Human , Humans , Human Genome Project , High-Throughput Nucleotide Sequencing/methods , Genetic Variation , Genomics/methods
2.
Nat Commun ; 15(1): 4007, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740805

ABSTRACT

Bimetallic catalysts combining precious and earth-abundant metals in well designed nanoparticle architectures can enable cost efficient and stable heterogeneous catalysis. Here, we present an interaction-driven in-situ approach to engineer finely dispersed Ni decorated Pt nanoparticles (1-6 nm) on perovskite nanofibres via reduction at high temperatures (600-800 oC). Deposition of Pt (0.5 wt%) enhances the reducibility of the perovskite support and promotes the nucleation of Ni cations via metal-support interaction, thereafter the Ni species react with Pt forming alloy nanoparticles, with the combined processes yielding smaller nanoparticles that either of the contributing processes. Tuneable uniform Pt-Ni nanoparticles are produced on the perovskite surface, yielding reactivity and stability surpassing 1 wt.% Pt/γ-Al2O3 catalysts for CO oxidation. This approach heralds the possibility of in-situ fabrication of supported bimetallic nanoparticles with engineered compositional distributions and performance.

3.
Behav Res Methods ; 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38630159

ABSTRACT

Can an inclusive test of face cognition meet or exceed the psychometric properties of a prominent less inclusive test? Here, we norm and validate an updated version of the influential Reading the Mind in the Eyes Test (RMET), a clinically significant neuropsychiatric paradigm that has long been used to assess theory of mind and social cognition. Unlike the RMET, our Multiracial Reading the Mind in the Eyes Test (MRMET) incorporates racially inclusive stimuli, nongendered answer choices, ground-truth referenced answers, and more accessible vocabulary. We show, via a series of large datasets, that the MRMET meets or exceeds RMET across major psychometric indices. Moreover, the reliable signal captured by the two tests is statistically indistinguishable, evidence for full interchangeability. We thus present the MRMET as a high-quality, inclusive, normed and validated alternative to the RMET, and as a case in point that inclusivity in psychometric tests of face cognition is an achievable aim. The MRMET test and our normative and validation data sets are openly available under a CC-BY-SA 4.0 license at osf.io/ahq6n.

4.
bioRxiv ; 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-36747613

ABSTRACT

Underrepresented populations are often excluded from genomic studies due in part to a lack of resources supporting their analyses. The 1000 Genomes Project (1kGP) and Human Genome Diversity Project (HGDP), which have recently been sequenced to high coverage, are valuable genomic resources because of the global diversity they capture and their open data sharing policies. Here, we harmonized a high quality set of 4,094 whole genomes from HGDP and 1kGP with data from the Genome Aggregation Database (gnomAD) and identified over 153 million high-quality SNVs, indels, and SVs. We performed a detailed ancestry analysis of this cohort, characterizing population structure and patterns of admixture across populations, analyzing site frequency spectra, and measuring variant counts at global and subcontinental levels. We also demonstrate substantial added value from this dataset compared to the prior versions of the component resources, typically combined via liftover and variant intersection; for example, we catalog millions of new genetic variants, mostly rare, compared to previous releases. In addition to unrestricted individual-level public release, we provide detailed tutorials for conducting many of the most common quality control steps and analyses with these data in a scalable cloud-computing environment and publicly release this new phased joint callset for use as a haplotype resource in phasing and imputation pipelines. This jointly called reference panel will serve as a key resource to support research of diverse ancestry populations.

5.
Neuron ; 111(18): 2800-2810.e5, 2023 09 20.
Article in English | MEDLINE | ID: mdl-37463579

ABSTRACT

Genetic association studies have made significant contributions to our understanding of the etiology of neurodevelopmental disorders (NDDs). However, these studies rarely focused on the African continent. The NeuroDev Project aims to address this diversity gap through detailed phenotypic and genetic characterization of children with NDDs from Kenya and South Africa. We present results from NeuroDev's first year of data collection, including phenotype data from 206 cases and clinical genetic analyses of 99 parent-child trios. Most cases met criteria for global developmental delay/intellectual disability (GDD/ID, 80.3%). Approximately half of the children with GDD/ID also met criteria for autism. Analysis of exome-sequencing data identified a pathogenic or likely pathogenic variant in 13 (17%) of the 75 cases from South Africa and 9 (38%) of the 24 cases from Kenya. Data from the trio pilot are publicly available, and the NeuroDev Project will continue to develop resources for the global genetics community.


Subject(s)
Autistic Disorder , Intellectual Disability , Neurodevelopmental Disorders , Humans , Child , Neurodevelopmental Disorders/genetics , Phenotype , Intellectual Disability/genetics , Autistic Disorder/genetics , Exome , Developmental Disabilities/genetics
6.
Mar Pollut Bull ; 192: 115006, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37172342

ABSTRACT

Given the urgent need for continuous and diverse research on marine fuel oils, this study investigated the effects of the properties of fuel oil on its adsorption to adsorbent materials. Very low-sulfur fuel oil (VLSFO), which is increasingly being utilized in vessels, was tested to simulate adsorption from seawater at temperatures of 1, 15, and 25 °C. Temperature minimally affected the adsorbed amount of low-viscosity VLSFOs and high-sulfur fuel oils. Conversely, the amount of high-viscosity VLSFO adsorbed decreased sharply at 1 and 15 °C. The viscosity, pour point, aromatics, asphaltenes, and wax contents of fuel oils determined the amounts adsorbed on an adsorbent. Therefore, at low sea surface temperatures associated with VLSFO spills, adsorption may be challenging. These findings highlight the need to improve fuel oil quality to accommodate spills in the marine environment.


Subject(s)
Fuel Oils , Petroleum Pollution , Water Pollutants, Chemical , Petroleum Pollution/analysis , Adsorption , Water Pollutants, Chemical/analysis , Temperature
7.
Dev Reprod ; 27(4): 213-220, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38292238

ABSTRACT

Previously, we showed that a chronic-low-dose nonylphenol (NP) exposure resulted in histological changes with sexually dimorphic pattern in rat adrenal glands. We hypothesized that such structural changes are closely related to the hormonal secretory patterns. To test this hypothesis, we developed the short-term adrenal incubation method, and measured the levels of catecholamines and cortical steroids using the high-performance liquid chromatography with electrochemical detection (HPLC-ECD) and specific enzyme-linked immunosorbent assay, respectively. The norepinephrine (NE) levels in media from NP-treated female adrenal, except 100 pM NP, were significantly increased [control (CTL) vs 1 nM NP, p<0.001; vs 10 nM NP, p<0.05; vs 100 nM NP, p<0.001; vs 1 µM NP, p<0.01]. The NE secretion from male adrenal was higher when treated with 100 nM and 1 µM NP (CTL vs 100 nM NP, p<0.05; vs 1 µM NP, p<0.05, respectively). The aldosterone level in the female adrenal media treated with 100 pM NP was significantly decreased, on the other hand, that of media treated with 10 nM NP was significantly increased (CTL vs 100 pM NP, p<0.05; vs 10 nM NP, p<0.01). In male adrenal media, the aldosterone levels of 10 nM, 100 nM and 1 µM NP-treated media were significantly declined (CTL vs 10 nM NP, p<0.001; vs 100 nM NP, p<0.001; vs 1 µM NP, p<0.001). These results showed the NP treatment altered secretory pattern of aldosterone from adrenals of both sexes, showing sexual dimorphism. It may be helpful for understanding possible adrenal pathophysiology, and endocrine disrupting chemicals-related sexually dimorphic phenomena in adrenals.

8.
Nanomaterials (Basel) ; 12(19)2022 Sep 24.
Article in English | MEDLINE | ID: mdl-36234453

ABSTRACT

To design metal nanoparticles (NPs) on a perovskite surface, the exsolution method has been extensively used for efficient catalytic reactions. However, there are still the challenges of finding a combination and optimization for the NPs' control. Thus, we report in situ control of the exsolved Ni NPs from perovskite to apply as a catalyst for dry reforming of methane (DRM). The La0.8Ce0.1Ti0.6Ni0.4O3 (LCTN) is designed by Ce doping to incorporate high amounts of Ni in the perovskite lattice and also facilitate the exsolution phenomenon. By control of the eluted Ni NPs through exsolution, the morphological properties of exsolved Ni NPs are observed to have a size range of 10~49 nm, while the reduction temperatures are changed. At the same time, the chemical structure of the eluted Ni NPs is also changed by an increased reduction temperature to a highly metallic Ni phase with an increased oxygen vacancy at the perovskite oxide surface. The optimized composite nanomaterial displays outstanding catalytic performance of 85.5% CH4 conversion to produce H2 with a value of 15.5 × 1011 mol/s·gcat at 60.2% CO conversion, which shows the importance of the control of the exsolution mechanism for catalytic applications.

9.
Ann Dermatol ; 34(2): 105-109, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35450312

ABSTRACT

Background: In South Korea, there have been few nationwide epidemiologic studies about premalignant actinic keratosis (AK), squamous cell carcinoma in situ (Bowen's disease), nonmelanoma skin cancer (NMSC), malignant melanoma of the skin (MM), Kaposi's sarcoma (KS), connective and soft tissue cancers, or mycosis fungoides (MF). Objective: Using a nationwide population-based study, we attempted to measure the incidence and the prevalence of the above-mentioned tumors in South Korea. Methods: The database we used included all claims in the Korean National Health Insurance program and the Korean Medical Aid program from 2008 to 2016. The International Classification of Diseases, 10th revision (ICD-10) was used to record diagnoses in this database. This data included AK, Bowen's disease, NMSC, MM, KS, connective and soft tissue cancers, and MF. Results: The age-standardized incidence and prevalence rate of AK, Bowen's disease, NMSC, MM, KS, connective and soft tissue cancers, as well as MF increased during the periods we investigated. The incidence and prevalence rate of AK and NMSC have increased two- to three-fold. In the case of Bowen's disease, MM, KS, connective and soft tissue cancers, or MF, we observed no significant tendency in age-standardized incidence or prevalence. Conclusion: We confirmed that the age-standardized incidence and prevalence rates of NMSC and AK tended to increase. These results might contribute to developing preventive and therapeutic strategies for skin cancers and may become a source for further studies.

10.
Dermatol Ther ; 35(2): e15222, 2022 02.
Article in English | MEDLINE | ID: mdl-34820982

ABSTRACT

Atmospheric-pressure, non-thermal plasma destroys microorganisms by directly reacting with hydrocarbon molecules in the cell wall and/or by damaging the cytoplasmic membrane, proteins, and DNA with charged particles and reactive species. The aim of our study was to evaluate the antibacterial and anticandidal effects of atmospheric-pressure, non-thermal, nitrogen- and argon-plasma pulses on various pathogen preparations. The resultant antibacterial and anticandidal effects were assessed by evaluating percent and log reduction values for pathogen colonies. Nitrogen-plasma pulses emitted at an energy of 1.5 J and argon-plasma pulses generated at 0.5 J elicited remarkable antibacterial effects on Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA) and anticandidal effects on Candida albicans. Nitrogen-plasma pulses at a pulse count of five elicited remarkable antibacterial effects on Cutibacterium acnes at the energy settings of 1.75, 2.5, and 3 J, but not at 1 J. Meanwhile, argon-plasma pulses showed antibacterial effects on C. acnes at an energy of 0.5 and 0.65 J. Nitrogen- or argon-plasma pulses exert antibacterial and anticandidal effects on bacterial and fungal pathogens.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Argon/pharmacology , Atmospheric Pressure , Humans , Nitrogen/pharmacology , Pseudomonas aeruginosa
11.
Dev Reprod ; 26(4): 175-182, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36817359

ABSTRACT

Previous studies, including our own, indicate that distinct morphological changes in rodent adrenal cortex could be induced by exposure of endocrine disrupting chemicals (EDC). In the present study, we conducted histological analyses of adrenocortical substructure using a nonylphenol-treated F1 rat model. The adrenal weight of NP-5000 group was significantly declined in female rats (p<0.001), while the adrenal weights of NP-treated groups were not significantly changed in male rats. The thickness of zona glomerulosa layers of female rats in NP-5000 group was significantly declined (p<0.001) but zona fasciculata layers were not changed. The zona reticularis layers of NP-treated group were significantly thinner than those of control group (NP-50, p<0.05; NP-5000, p<0.01). In male adrenal glands, there was no significant change of zona glomerulosa layers in NP-treated groups while the thickness of zona fasciculata in NP-5000 group was significantly decreased (p<0.01). Like female rats, the thickness of zona reticularis in NP-treated groups was significantly decreased (NP-50, p<0.001; NP-5000, p<0.05). Present study demonstrated that the adrenal histology could be altered by low-dose NP exposure in F1 rats, and the effect might be sexually dimorphic. Further study will be helpful for understanding possible adrenal pathophysiology induced by EDC exposure, and EDC-related sexually dimorphic phenomena in rodent adrenals.

12.
Curr Genet ; 67(6): 969-980, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34435216

ABSTRACT

Hydrogen peroxide (H2O2) is a debriding agent that damages the microbial structure and function by generating various reactive oxygen species (ROS). H2O2-produced hydroxyl radical (OH∙) also exerts oxidative stress on microorganisms. The spread of antibiotic-resistance in bacteria is a serious issue worldwide, and greater efforts are needed to identify and characterize novel antibacterial mechanisms to develop new treatment strategies. Therefore, this study aimed to clarify the relationship between H2O2 and Escherichia coli and to elucidate a novel antibacterial mechanism(s) of H2O2. Following H2O2 exposure, increased levels of 8-hydroxydeoxyguanosine and malondialdehyde indicated that H2O2 accelerates oxidation of bacterial DNA and lipids in E. coli. As oxidative damage worsened, the SOS response was triggered. Cell division arrest and resulting filamentous cells were identified in cells, indicating that LexA was involved in DNA replication. It was also verified that RecA, a representative SOS gene, helps self-cleavage of LexA and acts as a bacterial caspase-like protein. Our findings also showed that dinF is essential to preserve E. coli from H2O2-induced ROS, and furthermore, demonstrated that H2O2-induced SOS response and SOS genes participate differently in guarding E. coli from oxidative stress. As an extreme SOS response is considered apoptosis-like death (ALD) in bacteria, additional experiments were performed to examine the characteristics of ALD. DNA fragmentation and membrane depolarization appeared in H2O2-treated cells, suggesting that H2O2 causes ALD in E. coli. In conclusion, our investigations revealed that ALD is a novel antibacterial mode of action(s) of H2O2 with important contributions from SOS genes.


Subject(s)
Apoptosis/genetics , Escherichia coli Infections/microbiology , Escherichia coli/physiology , Hydrogen Peroxide/metabolism , SOS Response, Genetics , DNA Fragmentation , Gene Expression Regulation, Bacterial , Hydroxyl Radical/metabolism , Intracellular Space/metabolism , Lipid Peroxidation , Oxidative Stress , Reactive Oxygen Species/metabolism , Rec A Recombinases/genetics , Rec A Recombinases/metabolism
13.
IUBMB Life ; 73(7): 953-967, 2021 07.
Article in English | MEDLINE | ID: mdl-33934490

ABSTRACT

Naringin is a flavonoid which has a therapeutic effect. However, the details of its antifungal mechanism have not yet been fully elucidated. This study focused on clarifying the relationship between naringin and Candida albicans, to understand its mode of antifungal action. In general, naringin is an antioxidant, but our results indicated that 1 mM naringin generates intracellular superoxide (O2- ) and hydroxyl radicals (OH- ). Reactive oxygen species (ROS) have a serious impact on Ca2+ signaling and the production of mitochondrial ROS. After exposure to enhanced O2- and OH- , mitochondrial Ca2+ overload and mitochondrial O2- generation were confirmed in C. albicans. It was verified that mitochondrial O2- transforms mitochondrial glutathione (GSH) to oxidized GSH (GSSG), leading to extreme oxidative stress in mitochondria. The previously observed Ca2+ accumulation and oxidative stress resulted in mitochondrial membrane potential (MMP) alteration and increased mitochondrial mass. In succession, cytochrome c release from the mitochondria to the cytosol was detected due to MMP loss. Cytochrome c promotes the initiation of apoptosis, and further experiments were performed to assess the apoptotic hallmarks. Metacaspases activation, chromosomal condensation, DNA fragmentation, and phosphatidylserine exposure were observed, indicating that naringin induces apoptosis in C. albicans. In conclusion, our findings manifested that naringin-generated O2- and OH- damage the mitochondria and that mitochondrial dysfunction-mediated apoptosis is novel antifungal mechanism of naringin.


Subject(s)
Antifungal Agents/pharmacology , Candida albicans/drug effects , Flavanones/pharmacology , Mitochondria/drug effects , Calcium/metabolism , Candida albicans/cytology , Candida albicans/metabolism , Caspases/metabolism , Cytochromes c/metabolism , DNA Damage , Glutathione/metabolism , Membrane Potential, Mitochondrial/drug effects , Microbial Sensitivity Tests , Mitochondria/metabolism , Reactive Oxygen Species/metabolism
14.
Behav Res Methods ; 53(6): 2544-2557, 2021 12.
Article in English | MEDLINE | ID: mdl-33954913

ABSTRACT

Mobile- and web-based psychological research are a valuable addition to the set of tools available for scientific study, reducing logistical barriers for research participation and allowing the recruitment of larger and more diverse participant groups. However, this comes at the cost of reduced control over the technology used by participants, which can introduce new sources of variability into study results. In this study, we examined differences in measured performance on timed and untimed cognitive tests between users of common digital devices in 59,587 (Study 1) and 3818 (Study 2) visitors to TestMyBrain.org , a web-based cognitive testing platform. Controlling for age, gender, educational background, and cognitive performance on an untimed vocabulary test, users of mobile devices, particularly Android smartphones, showed significantly slower performance on tests of reaction time than users of laptop and desktop computers, suggesting that differences in device latency affect measured reaction times. Users of devices that differ in user interface (e.g. screen size, mouse vs. touchscreen) also show significant differences (p < 0.001) in measured performance on tests requiring fast reactions or fine motor movements. By quantifying the contribution of device differences to measured cognitive performance in an online setting, we hope to improve the accuracy of mobile- and web-based cognitive assessments, allowing these methods to be used more effectively.


Subject(s)
Computers, Handheld , Smartphone , Data Collection , Humans , Microcomputers , Neuropsychological Tests
15.
Biochem J ; 478(4): 855-869, 2021 02 26.
Article in English | MEDLINE | ID: mdl-33522568

ABSTRACT

Lupeol is known to be plentiful in fruits or plant barks and has an antimicrobial effect, however, its mode of action(s) has yet to be determined. To elucidate lupeol generates nitric oxide (NO), which is recognized for possessing an antimicrobial activity, intracellular NO was measured in Escherichia coli using DAF-FM. Using the properties of NO passing through plasma membrane easily, increased malondialdehyde levels have shown that lupeol causes lipid peroxidation, and the resulting membrane depolarization was confirmed by DiBAC4(3). These data indicated that lupeol-induced NO is related to the destruction of bacterial membrane. Further study was performed to examine whether NO, known as a cell proliferation inhibitor, affects bacterial cell division. As a result, DAPI staining verified that lupeol promotes cell division arrest, and followed by early apoptosis is observed in Annexin V/PI double staining. Even though these apoptotic hallmarks appeared, the endonuclease failed to perform properly with supporting data of decreased intracellular Mg2+ and Ca2+ levels without DNA fragmentation, which is confirmed using a TUNEL assay. These findings indicated that lupeol-induced NO occurs DNA fragmentation-independent bacterial apoptosis-like death (ALD). Additionally, lupeol triggers DNA filamentation and morphological changes in response to DNA repair system called SOS system. In accordance with the fact that ALD deems to SOS response, and that the RecA is considered as a caspase-like protein, increase in caspase-like protein activation occurred in E. coli wild-type, and no ΔRecA mutant. In conclusion, these results demonstrated that the antibacterial mode of action(s) of lupeol is an ALD while generating NO.


Subject(s)
Anti-Bacterial Agents/pharmacology , Apoptosis/drug effects , Escherichia coli/drug effects , Nitric Oxide/physiology , Pentacyclic Triterpenes/pharmacology , Calcium/metabolism , Cell Division , Cell Membrane/drug effects , Cell Membrane/metabolism , DNA Fragmentation , DNA, Bacterial/drug effects , DNA, Bacterial/metabolism , DNA-Binding Proteins/metabolism , Drug Evaluation, Preclinical , Escherichia coli/metabolism , Escherichia coli Proteins/metabolism , Lipid Peroxidation/drug effects , Magnesium/metabolism , Membrane Lipids/metabolism , Membrane Potentials/drug effects , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/biosynthesis , Norfloxacin/pharmacology , Rec A Recombinases/metabolism , SOS Response, Genetics
16.
RSC Adv ; 11(45): 27880-27896, 2021 Aug 16.
Article in English | MEDLINE | ID: mdl-35480732

ABSTRACT

Non-thermal plasma (NTP) is widely used in the disinfection and surface modification of biomaterials. NTP treatment can regenerate and improve skin function; however, its effectiveness on hair follicle (HF) growth and its underlying mechanisms need to be elucidated. Herein, we propose an air-based NTP treatment, which generates exogenous nitric oxide (eNO), as a therapeutic strategy for hair growth. The topical application of air-based NTP generates large amounts of eNO, which can be directly detected using a microelectrode NO sensor, in the dermis of mouse dorsal skin. Additionally, NTP-induced eNO has no cytotoxicity in normal human skin cells and promotes hair growth by increasing capillary tube formation, cellular proliferation, and hair/angiogenesis-related protein expression. Furthermore, NTP treatment promotes hair growth with adipogenesis and activation of CD34+CD44+ stem cells and improves the inter-follicular macroenvironment via increased perifollicular vascularity in the mouse hair regrowth model. Given the importance of the hair follicle (HF) cycle ratio (growth vs. regression vs. resting) in diagnosing alopecia, NTP treatment upregulates the stem cell activity of the HF to promote the anagen : catagen : telogen ratio, leading to improved hair growth. We confirmed the upregulation of increasing Wnt/ß-catenin signaling and activation of perifollicular adipose tissue and angiogenesis in HF regeneration. In conclusion, these results show that the eNO from NTP enhances the cellular activities of human skin cells and endothelial cells in vitro and stem cells in vivo, thereby increasing angiogenesis, adipogenesis, and hair growth in the skin dermis. Furthermore, the results of this study suggest that NTP treatment may be a highly efficient alternative in regenerative medicine for achieving enhanced hair growth.

17.
Appl Microbiol Biotechnol ; 104(24): 10711-10724, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33170329

ABSTRACT

Increasing prevalence of multidrug-resistant untreatable infections has prompted researchers to trial alternative treatments such as a substitute for traditional antibiotics. This study endeavored to elucidate the antibacterial mechanism(s) of this isoflavone, via analysis of relationship between genistein and Escherichia coli. Furthermore, this investigation analyzed whether genistein generates nitric oxide (NO) in E. coli as NO contributes to cell death. RecA, an essential protein for the bacterial SOS response, was detected through western blot, and the activated caspases decreased without RecA. The results showed that the NO induced by genistein affected the bacterial DNA. Under conditions of acute DNA damage, an SOS response called apoptosis-like death occurred, affecting DNA repair. These results suggested that RecA was bacterial caspase-like protein. In addition, NO was toxic to the bacterial cells and induced dysfunction of the plasma membrane. Thus, membrane depolarization and phosphatidylserine exposure were observed similarly to eukaryotic apoptosis. In conclusion, the combined results demonstrated that the antibacterial mode of action(s) of genistein was a NO-induced apoptosis-like death, and the role of RecA suggested that it contributed to the SOS response of NO defense. KEY POINTS: • Genistein generates nitric oxide in E. coli. • Genistein exhibits intense SOS response in E. coli. • Genistein-induced NO causes apoptosis-like death in E. coli.


Subject(s)
Escherichia coli Proteins , Escherichia coli , Apoptosis , Escherichia coli/genetics , Escherichia coli/metabolism , Escherichia coli Proteins/genetics , Genistein/pharmacology , Nitric Oxide , Rec A Recombinases/genetics , Rec A Recombinases/metabolism , SOS Response, Genetics
18.
Integr Cancer Ther ; 19: 1534735420932635, 2020.
Article in English | MEDLINE | ID: mdl-32571104

ABSTRACT

This study investigated the adjuvant effects for anticancer and antifatigue of the combination of Cordyceps militaris extract with sorafenib. The 5 extracts of C militaris were obtained through hexane, chloroform, ethyl acetate, butanol, and water and were evaluated for anticancer growth activity. Among these extracts, ethyl acetate extract of C militaris showed the best tumor growth inhibitory activity and the adjuvant effects in combination with sorafenib. As a result of biochemical analysis with serum, the combination of ethyl acetate extract of C militaris with sorafenib showed the adjuvant effects both improving hepatic function and relieving cancer-related fatigue. In addition, 1H-nuclear magnetic resonance-based metabolic profiling in liver tissues showed that the change of metabolism by ethyl acetate extract of C militaris with sorafenib was related with serum fatigue biomarkers. Therefore, the combination strategy such as ethyl acetate extraction of C militaris with sorafenib constitutes a promising therapeutic strategy in hepatocellular carcinoma, via the inhibition of cancer growth, the enhancement of liver function, as well as the alleviation of cancer-related fatigue.


Subject(s)
Cordyceps , Neoplasms , Acetates , Fatigue/drug therapy , Humans , Magnetic Resonance Spectroscopy
19.
Skin Res Technol ; 26(1): 81-90, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31532008

ABSTRACT

BACKGROUND: For medical purposes, plasma can be generated from inert gaseous sources in a device by ultra-high-frequency generators and emitted to target tissue at a pulse duration in the milliseconds. OBJECTIVE: To evaluate argon and nitrogen plasma pulse-induced tissue reactions in the skin and skin appendages of an in vivo animal model. METHODS: Argon and nitrogen plasma pulses were non-invasively delivered to in vivo rat skin at various experimental settings. Specimens were histologically evaluated following hematoxylin and eosin and Masson's trichrome staining. RESULTS: At low-energy settings of 1.0, 1.5, and 2.0 J, nitrogen plasma treatments generated noticeable tissue coagulation at the depths of 31.5 ± 8.3, 94.9 ± 16.9, and 171.6 ± 19.7 µm, respectively, at Day 0. At high-energy settings of 2.5 and 3.0 J, nitrogen plasma treatments generated marked tissue coagulation at the depths of 381.7 ± 33.6 µm and 456.3 ± 75.7 µm, respectively, at Day 0. CONCLUSIONS: Treatment with argon plasma induces microscopic changes in the epidermis, dermis, and sebaceous glands without generating excessive thermal injury, whereas that with nitrogen plasma elicits energy-dependent thermal coagulation in the epidermis and dermis with remarkable neocollagenesis.


Subject(s)
Gases/pharmacology , Skin/drug effects , Skin/pathology , Animals , Male , Rats , Rats, Sprague-Dawley
20.
Epidemiol Health ; 41: e2019044, 2019.
Article in English | MEDLINE | ID: mdl-31623421

ABSTRACT

OBJECTIVES: The aim of this study was to estimate the medical surge capacity required for mass prophylaxis based on a hypothetical outbreak of smallpox. METHODS: We performed a simulation using the Bioterrorism and Epidemic Outbreak Response Model and varied some important parameters, such as the number of core medical personnel and the number of dispensing clinics. RESULTS: Gaps were identified in the medical surge capacity of the Korean government, especially in the number of medical personnel who could respond to the need for mass prophylaxis against smallpox. CONCLUSIONS: The Korean government will need to train 1,000 or more medical personnel for such an event, and will need to prepare many more dispensing centers than are currently available.


Subject(s)
Disease Outbreaks/prevention & control , Mass Vaccination/organization & administration , Smallpox Vaccine/administration & dosage , Smallpox/prevention & control , Clinical Competence , Computer Simulation , Health Facilities/supply & distribution , Health Workforce/statistics & numerical data , Humans , Republic of Korea/epidemiology , Smallpox/epidemiology
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