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1.
Front Cell Infect Microbiol ; 14: 1410997, 2024.
Article in English | MEDLINE | ID: mdl-39027135

ABSTRACT

Background: Acinetobacter baumannii (AB) has emerged as one of the most challenging pathogens worldwide, causing invasive infections in the critically ill patients due to their ability to rapidly acquire resistance to antibiotics. This study aimed to analyze antibiotic resistance genes harbored in AB and non-baumannii Acinetobacter calcoaceticus-baumannii (NB-ACB) complex causing invasive diseases in Korean children. Methods: ACB complexes isolated from sterile body fluid of children in three referral hospitals were prospectively collected. Colistin susceptibility was additionally tested via broth microdilution. Whole genome sequencing was performed and antibiotic resistance genes were analyzed. Results: During January 2015 to December 2020, a total of 67 ACB complexes were isolated from sterile body fluid of children in three referral hospitals. The median age of the patients was 0.6 (interquartile range, 0.1-7.2) years old. Among all the isolates, 73.1% (n=49) were confirmed as AB and others as NB-ACB complex by whole genome sequencing. Among the AB isolates, only 22.4% susceptible to carbapenem. In particular, all clonal complex (CC) 92 AB (n=33) showed multi-drug resistance, whereas 31.3% in non-CC92 AB (n=16) (P<0.001). NB-ACB showed 100% susceptibility to all classes of antibiotics except 3rd generation cephalosporin (72.2%). The main mechanism of carbapenem resistance in AB was the bla oxa23 gene with ISAba1 insertion sequence upstream. Presence of pmr gene and/or mutation of lpxA/C gene were not correlated with the phenotype of colistin resistance of ACB. All AB and NB-ACB isolates carried the abe and ade multidrug efflux pumps. Conclusions: In conclusion, monitoring and research for resistome in ACB complex is needed to identify and manage drug-resistant AB, particularly CC92 AB carrying the bla oxa23 gene.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Anti-Bacterial Agents , Microbial Sensitivity Tests , Whole Genome Sequencing , Humans , Child , Child, Preschool , Infant , Republic of Korea/epidemiology , Acinetobacter Infections/microbiology , Acinetobacter Infections/epidemiology , Acinetobacter baumannii/genetics , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/isolation & purification , Anti-Bacterial Agents/pharmacology , Female , Male , COVID-19/epidemiology , Colistin/pharmacology , Acinetobacter calcoaceticus/genetics , Acinetobacter calcoaceticus/drug effects , Acinetobacter calcoaceticus/isolation & purification , Drug Resistance, Bacterial/genetics , Drug Resistance, Multiple, Bacterial/genetics , SARS-CoV-2/genetics , SARS-CoV-2/drug effects , Prospective Studies , beta-Lactamases/genetics , beta-Lactamases/metabolism
2.
J Korean Med Sci ; 39(15): e136, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38651222

ABSTRACT

BACKGROUND: Haemophilus influenzae is a frequently encountered pathogen responsible for respiratory tract infections in children. Following the detection of ceftriaxone-resistant H. influenzae at our institution, we aimed to investigate the resistance mechanisms of ceftriaxone in H. influenzae, with a particular focus on alterations in penicillin-binding protein 3 (PBP3) and ß-lactamase production. METHODS: Among H. influenzae isolates collected at Asan Medical Center Children's Hospital from March 2014 to April 2019, ceftriaxone-resistant strains by the disk-diffusion test were included. Ceftriaxone minimum inhibitory concentrations (MICs) were determined using the E-test according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The presence of ß-lactamase was assessed through cefinase test and TEM-1/ROB-1 polymerase chain reaction (PCR). PBP3 alterations were explored via ftsI gene sequencing. RESULTS: Out of the 68 collected strains, 21 exhibited resistance to ceftriaxone in disk diffusion tests. Two strains were excluded due to failed subculture. Among 19 ceftriaxone-resistant H. influenzae isolates, eighteen were non-typeable H. influenzae, and twelve were positive for TEM-1 PCR. Isolates were classified into groups II (harboring only N526K, n = 3), III (N526K+S385T, n = 2), III+ (S385T+L389F+N526K, n = 11), and III-like+ (S385T+L389F+R517H, n = 3) according to the PBP3 alteration pattern. With a median ceftriaxone MIC of 0.190 mg/L (range, 0.008-0.750), the median ceftriaxone MIC was the highest in group III-like+ (0.250 mg/L), followed by groups III+ (0.190 mg/L), III (0.158 mg/L), and II (0.012 mg/L). All three strains belonging to group II, which did not harbor the S385T substitution, had ceftriaxone MICs of ≤ 0.125 mg/L. CONCLUSION: The emergence of ceftriaxone-resistant H. influenzae with ceftriaxone MIC values of up to 0.75 mg/L was observed even in children in South Korea, with most associated with S385T and L389F substitutions. The N526K mutation alone does not significantly impact ceftriaxone resistance. Further large-scale studies are essential to investigate changes in antibiotic resistance patterns and factors influencing antibiotic resistance in H. influenzae isolated from pediatric patients in Korea.


Subject(s)
Anti-Bacterial Agents , Ceftriaxone , Haemophilus Infections , Haemophilus influenzae , Microbial Sensitivity Tests , beta-Lactamases , Ceftriaxone/pharmacology , Haemophilus influenzae/drug effects , Haemophilus influenzae/isolation & purification , Haemophilus influenzae/genetics , Humans , Anti-Bacterial Agents/pharmacology , Republic of Korea , beta-Lactamases/genetics , beta-Lactamases/metabolism , Child , Haemophilus Infections/microbiology , Haemophilus Infections/drug therapy , Penicillin-Binding Proteins/genetics , Child, Preschool , Drug Resistance, Bacterial , Infant , Female , Male , Bacterial Proteins/genetics , Bacterial Proteins/metabolism
3.
BMC Infect Dis ; 24(1): 259, 2024 Feb 24.
Article in English | MEDLINE | ID: mdl-38402154

ABSTRACT

BACKGROUND: While there is a high burden of methicillin-resistant Staphylococcus aureus (MRSA) infections among pediatric patients, studies on the molecular epidemiology of MRSA infections in Korean children since the 2010s are lacking. This study aimed to investigate the molecular genotypes and clinical characteristics of MRSA isolates from children with MRSA bacteremia at Asan Medical Center Children's Hospital from 2016 to 2021. METHODS: Clinical data were retrospectively reviewed, and the molecular types of MRSA were determined using multilocus sequence typing (MLST) and Staphylococcal cassette chromosome mec (SCCmec) typing. RESULTS: The overall methicillin resistance rate of S. aureus bacteremia was 44.8% (77/172); 49.5% in the period 2016-2018 (period 1) and 37.3% in the period 2019-2021 (period 2) (P = 0.116). Community-acquired infections accounted for only 3.9% of cases. The predominant ST group was ST72 group (67.6%), followed by ST5 group (18.9%) and ST1 group (5.4%). The proportion of ST5 was significantly lower in period 2 compared to period 1 (P = 0.02). Compared to the ST5 and ST1 groups, the ST72 group exhibited lower overall antibiotic resistance and multidrug-resistant (MDR) rates (12.0% [6/50] in ST72 group vs. 100.0% [14/14] in ST5 group vs. 50.0% [2/4] in ST1 group; P < 0.001). In the multivariate analysis, the ST1 group was an independent risk factor for 30-day all-cause mortality (aOR, 44.12; 95% CI, 3.46-562.19). CONCLUSION: The ST72-MRSA strain remained the most frequently isolated genotype in Korean children, while the ST1 group emerged as an independent risk factor for 30-day all-cause mortality in pediatric MRSA bacteremia. Ongoing efforts to uncover the evolving epidemiology of MRSA are essential for developing effective strategies for prevention and treatment.


Subject(s)
Bacteremia , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Child , Staphylococcus aureus , Molecular Epidemiology , Multilocus Sequence Typing , Retrospective Studies , Staphylococcal Infections/epidemiology , Microbial Sensitivity Tests , Bacteremia/epidemiology , Genotype , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use
4.
Biochem Biophys Res Commun ; 696: 149469, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38194806

ABSTRACT

Accumulating data suggest that ribosomal protein S6 kinase 1 (S6K1), an effector in the mammalian target of rapamycin (mTOR) pathway, plays pleiotropic roles in tumor progression. However, to date, while the tumorigenic function of S6K1 in tumor cells has been well elucidated, its role in the tumor stroma remains poorly understood. We recently showed that S6K1 mediates vascular endothelial growth factor A (VEGF-A) production in macrophages, thereby supporting tumor angiogenesis and growth. As macrophage-derived VEGF-A is crucial for both tumor cell intravasation and extravasation across the vascular endothelium, our previous findings suggest that stromal S6K1 signaling is required for tumor metastatic spread. Therefore, we aimed to determine the impact of host S6K1 depletion on tumor metastasis using a murine model of pulmonary metastasis (S6k1-/- mice implanted with B16F10 melanoma). The ablation of S6K1 in the host microenvironment significantly reduced the metastasized B16F10 melanoma cells on the lung surface in both spontaneous and intravenous lung metastasis mouse models without affecting the incidence of metastasis to distant lymph nodes. In addition, stromal S6K1 loss decreased the number of tumor cells circulating in the peripheral blood of mice bearing B16F10 xenografts without affecting the vascular leakage induced by VEGF-A in vivo. These observations demonstrate that S6K1 signaling in host cells other than endothelial cells is required to modulate the host microenvironment to facilitate the metastatic spread of tumors via blood circulation, thus revealing its novel role in the tumor stroma during tumor progression.


Subject(s)
Lung Neoplasms , Melanoma , Ribosomal Protein S6 Kinases, 90-kDa , Animals , Humans , Mice , Endothelial Cells/metabolism , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Mammals/metabolism , Melanoma/metabolism , Melanoma/pathology , Signal Transduction , Tumor Microenvironment , Vascular Endothelial Growth Factor A/metabolism , Ribosomal Protein S6 Kinases, 90-kDa/metabolism
5.
Sci Adv ; 9(44): eadj0461, 2023 Nov 03.
Article in English | MEDLINE | ID: mdl-37910607

ABSTRACT

The automation of organic compound synthesis is pivotal for expediting the development of such compounds. In addition, enhancing development efficiency can be achieved by incorporating autonomous functions alongside automation. To achieve this, we developed an autonomous synthesis robot that harnesses the power of artificial intelligence (AI) and robotic technology to establish optimal synthetic recipes. Given a target molecule, our AI initially plans synthetic pathways and defines reaction conditions. It then iteratively refines these plans using feedback from the experimental robot, gradually optimizing the recipe. The system performance was validated by successfully determining synthetic recipes for three organic compounds, yielding that conversion rates that outperform existing references. Notably, this autonomous system is designed around batch reactors, making it accessible and valuable to chemists in standard laboratory settings, thereby streamlining research endeavors.

6.
Pharmaceuticals (Basel) ; 16(9)2023 Sep 06.
Article in English | MEDLINE | ID: mdl-37765069

ABSTRACT

Artificial intelligence (AI) has permeated various sectors, including the pharmaceutical industry and research, where it has been utilized to efficiently identify new chemical entities with desirable properties. The application of AI algorithms to drug discovery presents both remarkable opportunities and challenges. This review article focuses on the transformative role of AI in medicinal chemistry. We delve into the applications of machine learning and deep learning techniques in drug screening and design, discussing their potential to expedite the early drug discovery process. In particular, we provide a comprehensive overview of the use of AI algorithms in predicting protein structures, drug-target interactions, and molecular properties such as drug toxicity. While AI has accelerated the drug discovery process, data quality issues and technological constraints remain challenges. Nonetheless, new relationships and methods have been unveiled, demonstrating AI's expanding potential in predicting and understanding drug interactions and properties. For its full potential to be realized, interdisciplinary collaboration is essential. This review underscores AI's growing influence on the future trajectory of medicinal chemistry and stresses the importance of ongoing synergies between computational and domain experts.

7.
J Korean Med Sci ; 38(33): e252, 2023 Aug 21.
Article in English | MEDLINE | ID: mdl-37605494

ABSTRACT

BACKGROUND: Ralstonia mannitolilytica is a causative organism of nosocomial infections, particularly associated with contaminated water, and resistant to various antibiotics, including carbapenems. Several clusters of R. mannitolilytica infections appeared in children at our institute from August 2018 to November 2019. METHODS: From March 2009 to March 2023, all patients admitted to Asan Medical Center Children's Hospital in Seoul, Korea, with culture-confirmed R. mannitolilytica and corresponding clinical signs of infection were identified. Epidemiological and environmental investigations were conducted. Polymerase chain reaction (PCR) was performed for the genes of OXA-443 and OXA-444 on R. mannitolilytica isolates. RESULTS: A total of 18 patients with R. mannitolilytica infection were included in this study, with 94.4% (17/18) and 5.6% (1/18) being diagnosed with pneumonia and central line-associated bloodstream infection, respectively. All-cause 30-day mortality rate was 61.1% (11/18), and seven of the fatal cases were caused by R. mannitolilytica infection itself. The resistance rates to meropenem and imipenem werew 94.4% (17/18) and 5.6% (1/18), respectively. Although four out of nine meropenem-resistant R. mannitolilytica isolates had positive PCR results for OXA-443 and OXA-444 genes, there were no significant differences in antimicrobial susceptibility patterns. Environmental sampling identified R. mannitolylica at two sites: a cold-water tap of a water purifier and an exhalation circuit of a patient mechanical ventilator. After implementing and improving adherence to infection control policies, no additional R. mannitolilytica infection cases have been reported since December 2019. CONCLUSION: R. mannitolilytica can cause life-threatening infections with high mortality in fragile pediatric populations. To prevent outbreaks, healthcare workers should be aware of R. mannitolilytica infections and strive to comply with infection control policies.


Subject(s)
Anti-Bacterial Agents , Disease Outbreaks , Humans , Child , Meropenem/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Hospitals, Pediatric
8.
Sensors (Basel) ; 23(12)2023 Jun 12.
Article in English | MEDLINE | ID: mdl-37420693

ABSTRACT

Solubility measurements are essential in various research and industrial fields. With the automation of processes, the importance of automatic and real-time solubility measurements has increased. Although end-to-end learning methods are commonly used for classification tasks, the use of handcrafted features is still important for specific tasks with the limited labeled images of solutions used in industrial settings. In this study, we propose a method that uses computer vision algorithms to extract nine handcrafted features from images and train a DNN-based classifier to automatically classify solutions based on their dissolution states. To validate the proposed method, a dataset was constructed using various solution images ranging from undissolved solutes in the form of fine particles to those completely covering the solution. Using the proposed method, the solubility status can be automatically screened in real time by using a display and camera on a tablet or mobile phone. Therefore, by combining an automatic solubility changing system with the proposed method, a fully automated process could be achieved without human intervention.


Subject(s)
Algorithms , Neural Networks, Computer , Humans , Solubility , Automation
9.
J Liver Cancer ; 23(2): 341-349, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37488925

ABSTRACT

BACKGROUND/AIM: Cancer-associated fibroblasts (CAFs) play an immunosuppressive role in the tumor microenvironment (TME) of human cancers; however, their characteristics and role in hepatocellular carcinoma (HCC) remain to be elucidated. METHODS: Nine tumor and surrounding liver tissue samples from patients with HCC who underwent surgery were used to isolate patient-derived CAFs. Cell morphology was observed using an optical microscope after culture, and cell phenotypes were evaluated using flow cytometry and immunoblotting. Cytokines secreted by CAFs into culture medium were quantified using a multiplex cytokine assay. RESULTS: CAFs were abundant in the TME of HCC and were adjacent to immune cells. After culture, the CAFs and non-tumor fibroblasts exhibited spindle shapes. We observed a robust expression of alpha-smooth muscle actin and fibroblast activation protein in CAFs, whereas alpha-fetoprotein, epithelial cell adhesion molecule, platelet/endothelial cell adhesion molecule-1, and E-cadherin were not expressed in CAFs. Furthermore, CAFs showed high secretion of various cytokines, namely C-X-C motif chemokine ligand 12, interleukin (IL)-6, IL-8, and C-C motif chemokine ligand 2. CONCLUSIONS: CAFs are abundant in the TME of HCC and play a crucial role in tumor progression. These fibroblasts secrete cytokines that promote tumor growth and metastasis.

10.
Pain Pract ; 23(1): 123-126, 2023 01.
Article in English | MEDLINE | ID: mdl-35638334

ABSTRACT

BACKGROUND: Lumbar spinal stenosis is a common degenerative disease that causes low back and lower-extremity pain that increases with age. The treatment of lumbar spinal stenosis is either conservative or surgical. ESI is a commonly performed conservative treatment, but evidence of its effectiveness in lumbar spinal stenosis is limited. CASE SERIES: We encountered the three patients with back pain and claudication due to lumbar spinal stenosis, which could not be controlled by conservative therapy including ESIs. Trimacinolone acetonide was injected into the patients' ligamentum flavum. All patients experienced dramatic improvement in their symptoms. CONCLUSIONS: Trimacinolone acetonide injection into the ligamentum flavum may be effective for lumbar spinal stenosis that does not improve with ESIs.


Subject(s)
Ligamentum Flavum , Pain, Intractable , Spinal Stenosis , Humans , Spinal Stenosis/complications , Spinal Stenosis/drug therapy , Pain Management/methods , Steroids/therapeutic use , Lumbar Vertebrae/surgery
11.
Int J Nanomedicine ; 17: 6317-6334, 2022.
Article in English | MEDLINE | ID: mdl-36536939

ABSTRACT

Background: Ototoxicity currently has no available treatment other than medication withdrawal as soon as toxicity is suspected. The human inner ear organs have little potential for regeneration; thus, ototoxicity-induced hair cell injury is deemed permanent. Dexamethasone (Dexa) is a synthetic steroid analog that has significant potential for otoprotection in the treatment of various inner ear diseases; however, its low absorption into the inner ear prevents significant recovery of function. Nanoparticles facilitate targeted drug delivery, stabilize drug release, and increase half-life of the drug. Methods: This study aimed to develop poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded superparamagnetic iron oxide nanoparticles (SPIONs) and Dexa (PSD-NPs) to control localized drug delivery by magnetic attraction in the treatment of ototoxicity-induced hearing loss. PSD-NPs and without SPIONs (PD-NPs) were prepared using a nanoprecipitation method. Results: Using an inner ear simulating system, we confirmed that PSD-NPs has an otoprotective effect in organotypic culture that is enhanced by magnetic attraction. PSD-NPs delivered via intrabullar injection in a magnetic field penetrated the inner ear and prevented hearing loss progression to a greater degree than equivalent doses of Dexa or PSD-NPs alone (day 28: ototoxic: 80.0 ± 0.0 dB; Dexa 100: 60.0 ± 15.5 dB; PSD 100: 50.0 ± 8.2 dB; PSD 100 with magnet: 22.5 ± 5.0 dB; P < 0.05). The protective effects were confirmed in various in vivo and in vitro models of ototoxicity. Conclusion: Our findings suggest that SPIONs with Dexa and magnetic field application prevent the progression of ototoxicity-induced hearing loss through anti-apoptotic mechanisms in the inner ear.


Subject(s)
Hearing Loss , Nanoparticles , Ototoxicity , Mice , Humans , Animals , Disease Models, Animal , Magnetic Iron Oxide Nanoparticles , Dexamethasone/pharmacology , Magnetic Phenomena
12.
Biomater Res ; 26(1): 58, 2022 Oct 22.
Article in English | MEDLINE | ID: mdl-36273198

ABSTRACT

BACKGROUND: Recombinant tissue plasminogen activator (rtPA) has a short half-life, and additional hemorrhagic transformation (HT) can occur when treatment is delayed. Here, we report the design and thrombolytic performance of 3 [Formula: see text]m discoidal polymeric particles loaded with rtPA and superparamagnetic iron oxide nanoparticles (SPIONs), referred to as rmDPPs, to address the HT issues of rtPA. METHODS: The rmDPPs consisted of a biodegradable polymeric matrix, rtPA, and SPIONs and were synthesized via a top-down fabrication. RESULTS: The rmDPPs could be concentrated at the target site with magnetic attraction, and then the rtPA could be released under acoustic stimulus. Therefore, we named that the particles had magnetoacoustic properties. For the in vitro blood clot lysis, the rmDPPs with magnetoacoustic stimuli could not enhance the lytic potential compared to the rmDPPs without stimulation. Furthermore, although the reduction of the infarcts in vivo was observed along with the magnetoacoustic stimuli in the rmDPPs, more enhancement was not achieved in comparison with the rtPA. A notable advantage of rmDPPs was shown in delayed administration of rmDPPs at poststroke. The late treatment of rmDPPs with magnetoacoustic stimuli could reduce the infarcts and lead to no additional HT issues, while rtPA alone could not show any favorable prognosis. CONCLUSION: The rmDPPs may be advantageous in delayed treatment of thrombotic patients.

13.
J Korean Med Sci ; 36(36): e246, 2021 Sep 13.
Article in English | MEDLINE | ID: mdl-34519187

ABSTRACT

In 2017, the Korean government launched an unprecedentedly large-scaled latent tuberculosis infection (LTBI) screening project which covered more than a million individuals in congregate settings. A total of 1,047,689 participants of source population (n = 2,336,157) underwent LTBI testing from 2017 to 2018. The overall LTBI test uptake rate during this project was 44.8%. Workers in daycare centers (83.5%) and kindergartens (78.9%) showed high participation rate. A total of 1,012,206 individuals with valid results of interferon-gamma release assay (IGRA) were selected to constitute the IGRA cohort. Most of the enrolled participants in the IGRA cohort were in their working age. Approximately, three-quarters of total enrolled population were female. Investigating the LTBI prevalence, stages of LTBI care cascade, natural history of LTBI, efficacy of LTBI treatment and cost-effectiveness of LTBI screening are feasible within this IGRA cohort.


Subject(s)
Interferon-gamma Release Tests/methods , Latent Tuberculosis/diagnosis , Mass Screening/economics , Adult , Antitubercular Agents/therapeutic use , Cohort Studies , Cost-Benefit Analysis , Female , Humans , Latent Tuberculosis/drug therapy , Male , Middle Aged , Prevalence , Republic of Korea
14.
Bioorg Med Chem ; 45: 116312, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34332211

ABSTRACT

Phosphatidylinositol 3-kinases (PI3Ks) mediate intracellular signal transduction. Aberrant PI3K signaling is associated with oncogenesis and disease progression in solid tumors and hematologic malignancies. Idelalisib (1), a first-in-class PI3Kδ inhibitor for the treatment of hematologic malignancies, was developed, but its sales were limited by black box warnings due to unexpected adverse effects. Therefore, to overcome these adverse events, various quinazolinone derivatives were synthesized and evaluated in vitro based on their inhibitory activity against the PI3K enzyme and the viability of cell lines such as MOLT and SUDHL. Among them, 6f (IC50 = 0.39 nM) and 6m (IC50 = 0.09 nM) showed excellent enzyme activity, and 6m displayed an approximately four-fold higher selectivity for PI3Kγ/δ compared with Idelalisib (1). Furthermore, in vivo PK experiments with 6f and 6m revealed that 6f (AUClast = 81.04 h*ng/mL, Cmax = 18.34 ng/mL, Tmax = 0.5 h, t1/2 = 10.2 h in 1 mpk dose) had improved PK compared with 1. Finally, further experiments will be conducted with 6f selected as a candidate, and the potential for it to be developed as a treatment with good efficacy for hematologic malignancies will be determined.


Subject(s)
Antineoplastic Agents/pharmacology , Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors , Hematologic Neoplasms/drug therapy , Phosphoinositide-3 Kinase Inhibitors/pharmacology , Purines/pharmacology , Quinazolinones/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Class I Phosphatidylinositol 3-Kinases/metabolism , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Hematologic Neoplasms/metabolism , Hematologic Neoplasms/pathology , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Molecular Structure , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Phosphoinositide-3 Kinase Inhibitors/chemical synthesis , Phosphoinositide-3 Kinase Inhibitors/chemistry , Purines/chemistry , Quinazolinones/chemical synthesis , Quinazolinones/chemistry , Structure-Activity Relationship
15.
Int J Biol Macromol ; 158: 443-451, 2020 Apr 29.
Article in English | MEDLINE | ID: mdl-32360470

ABSTRACT

The structural complexity of lignins necessitates characterization and isolation methodologies for assessing their appropriateness for thermo-chemical systems and material applications. Lignins prepared via two pulping methods (organosolv and soda) were comprehensively investigated by analyzing the properties, including lignin purity, yield, and thermal and chemical properties. The extracted organosolv lignin has high purity (93.13-98.12%), however, the purity of soda lignin was relatively low (87.58-89.61%). Organosolv lignin produced the highest heating value of 26.79-26.95 MJ kg-1, with a fixed carbon content of 39.47-41.06 wt%, high purity, and low ash content, making it suitable for biofuel applications. The content of total phenolic OH groups was higher for the organosolv lignins; however, for the phenolic OH groups, the 4-vinylphenol content was significantly higher in the soda lignins, and increased with increasing NaOH concentration. Overall, the thermal and chemical properties related to the lignin structure changed with the fractionation method and solvent concentration, which in turn influences the design of lignin valorization strategies for prospective depolymerization and material applications.

16.
Proc Natl Acad Sci U S A ; 116(39): 19288-19293, 2019 09 24.
Article in English | MEDLINE | ID: mdl-31501346

ABSTRACT

Bacterial cellulose nanofiber (BCNF) with high thermal stability produced by an ecofriendly process has emerged as a promising solution to realize safe and sustainable materials in the large-scale battery. However, an understanding of the actual thermal behavior of the BCNF in the full-cell battery has been lacking, and the yield is still limited for commercialization. Here, we report the entire process of BCNF production and battery manufacture. We systematically constructed a strain with the highest yield (31.5%) by increasing metabolic flux and improved safety by introducing a Lewis base to overcome thermochemical degradation in the battery. This report will open ways of exploiting the BCNF as a "single-layer" separator, a good alternative to the existing chemical-derived one, and thus can greatly contribute to solving the environmental and safety issues.

17.
Int J Mol Sci ; 20(16)2019 Aug 13.
Article in English | MEDLINE | ID: mdl-31412537

ABSTRACT

In this study, we synthesized a Zr-89-labeled anti-adenosine triphosphate synthase monoclonal antibody (ATPS mAb) for applications in immuno-positron emission tomography (PET) and evaluated its feasibility for angiogenesis imaging. The cellular uptake of Zr-89 ATPS mAb was measured after treatment of cancer cell lines in vitro, and its biodistribution was evaluated at 4, 24 and 48 h in vivo in mice bearing xenografts. PET images were acquired at 4, 24, 48, and 96 h after Zr-89 ATPS mAb administration. Tumor angiogenesis was analyzed using anti-CD31 immunofluorescence staining. The cellular uptake of Zr-89 ATPS mAb increased over time in MDA-MB-231 breast cancer cells but did not increase in PC3 prostate cancer cells. The tumor uptake of Zr-89 ATPS mAb at 24 h was 9.4 ± 0.9% ID/g for MDA-Mb-231 cells and was 3.8 ± 0.6% ID/g for PC3 cells (p = 0.004). Zr-89 ATPS mAb uptake in MDA-MB-231 xenografts was inhibited by the administration of cold ATPS mAb (4.4 ± 0.5% ID/g, p = 0.011). Zr-89 ATPS mAb uptake could be visualized by PET for up to 96 h in MDA-MB-231 tumors. In contrast, there was no distinct tumor uptake detected by PET in the PC3 xenograft model. CD31-positive tumor vessels were abundant in MDA-MB-231 tumors, whereas they were scarcely detected in PC3 tumors. In conclusion, ATPS mAb was successfully labeled with Zr-89, which could be used for immuno-PET imaging targeting tumor angiogenesis.


Subject(s)
Adenosine Triphosphate , Molecular Imaging , Neoplasms/diagnostic imaging , Neoplasms/pathology , Neovascularization, Pathologic/diagnostic imaging , Positron-Emission Tomography , Radioisotopes , Radiopharmaceuticals , Zirconium , Adenosine Triphosphate/metabolism , Animals , Antibodies, Monoclonal , Cell Line, Tumor , Disease Models, Animal , Female , Heterografts , Humans , Immunoconjugates , Male , Mice , Molecular Imaging/methods , Positron-Emission Tomography/methods , Radioisotopes/chemistry , Radioisotopes/metabolism , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/metabolism , Tissue Distribution , Zirconium/chemistry , Zirconium/metabolism
18.
Nutrients ; 11(5)2019 May 24.
Article in English | MEDLINE | ID: mdl-31137609

ABSTRACT

Obesity is one of major health challenges in the industrial world. Although rice hull has been reported to show various bioactivities, no studies have evaluated its anti-obesity effect. We hope to demonstrate the anti-obesity effect of rice hull extract (RHE) and the underlying mechanism in high-fat diet (HFD)-induced obese mice and 3T3-L1 preadipocytes. Serum lipid profiles were determined by enzymatic methods. Histological analysis of liver and epididymis fat tissues was carried out with hematoxylin and eosin stain. The mRNA expression of adipogenic markers was analyzed with qRT-PCR and western blotting. Oral administration of RHE reduced body weight gain and fat accumulation in HFD-fed mice. RHE also reduced lipid accumulation by inhibiting the mRNA expression of adipogenic-related genes in HFD-fed obese mice and differentiated preadipocytes. The downregulation of adipogenesis by RHE was mediated through the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). In addition, RHE induced the phosphorylation of c-Jun N-terminal kinases (JNK) and extracellular-signal-regulated kinases (ERK) in liver and epididymis adipose tissues of HFD-fed obese mice. Taken together, these findings indicate that RHE could inhibit the differentiation of adipose cell and prevent HFD-induced obesity, suggesting its potential in the prevention of obesity and metabolic syndrome and related-disorders.


Subject(s)
Adipocytes/drug effects , Adipogenesis/drug effects , Adiposity/drug effects , Anti-Obesity Agents/pharmacology , Diet, High-Fat , Obesity/prevention & control , Oryza , Plant Extracts/pharmacology , Seeds , 3T3-L1 Cells , AMP-Activated Protein Kinases/metabolism , Adipocytes/metabolism , Adipocytes/pathology , Adipogenesis/genetics , Animals , Anti-Obesity Agents/isolation & purification , Disease Models, Animal , Lipids/blood , Male , Mice , Mice, Inbred C57BL , Mitogen-Activated Protein Kinases/metabolism , Obesity/blood , Obesity/pathology , Obesity/physiopathology , Oryza/chemistry , Phosphorylation , Plant Extracts/isolation & purification , Seeds/chemistry , Signal Transduction , Weight Gain/drug effects
19.
J Phys Ther Sci ; 30(8): 958-959, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30154580

ABSTRACT

[Purpose] The purpose of this research was to examine differences in muscle activity between the resting forearm position (RFP) and the straight forearm position (SFP) during upper arm strengthening exercises. [Participants and Methods] In total, 35 healthy college students were randomly sampled (18 males and 17 females). Surface electromyography data were collected from the medial and lateral sides of the biceps and triceps brachii muscles. [Results] The medial muscles showed greater activity during SFP versus RFP, but no difference in overall activation was found between the two positions. [Conclusion] Carrying angle less affected to biceps and triceps brachii muscles activation during upper arm strengthening exercises.

20.
Food Microbiol ; 61: 72-82, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27697172

ABSTRACT

Prokaryotes were extracted from skates and fermented skates purchased from fish markets and a local manufacturer in South Korea. The prokaryotic community composition of skates and fermented skates was investigated using 16S rRNA pyrosequencing. The ranges for pH and salinity of the grinded tissue extract from fermented skates were 8.4-8.9 and 1.6-6.6%, respectively. Urea and ammonia concentrations were markedly low and high, respectively, in fermented skates compared to skates. Species richness was increased in fermented skates compared to skates. Dominant and predominant bacterial groups present in the fermented skates belonged to the phylum Firmicutes, whereas those in skates belonged to Gammaproteobacteria. The major taxa found in Firmicutes were Atopostipes (Carnobacteriaceae, Lactobacillales) and/or Tissierella (Tissierellaceae, Tissierellales). A combination of RT-PCR and pyrosequencing for active bacterial composition showed that the dominant taxa i.e., Atopostipes and Tissierella, were active in fermented skate. Those dominant taxa are possibly marine lactic acid bacteria. Marine bacteria of the taxa Lactobacillales and/or Clostridia seem to be important in alkaline fermentation of skates.


Subject(s)
Bacteria/isolation & purification , Fermentation , Microbial Consortia , Seafood/microbiology , Skates, Fish/microbiology , Animals , Bacteria/classification , Bacteria/genetics , Clostridium/genetics , Clostridium/isolation & purification , Firmicutes/genetics , Firmicutes/isolation & purification , High-Throughput Nucleotide Sequencing , Hydrogen-Ion Concentration , Lactobacillales/genetics , Lactobacillales/isolation & purification , Microbial Consortia/genetics , Republic of Korea
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