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1.
Eur J Pharmacol ; 973: 176573, 2024 Jun 15.
Article En | MEDLINE | ID: mdl-38642669

Parkinson's disease (PD) is characterised by severe movement defects and the degeneration of dopaminergic neurones in the midbrain. The symptoms of PD can be managed with dopamine replacement therapy using L-3, 4-dihydroxyphenylalanine (L-dopa), which is the gold standard therapy for PD. However, long-term treatment with L-dopa can lead to motor complications. The central renin-angiotensin system (RAS) is associated with the development of neurodegenerative diseases in the brain. However, the role of the RAS in dopamine replacement therapy for PD remains unclear. Here, we tested the co-treatment of the angiotensin-converting enzyme inhibitor (ACEI) with L-dopa altered L-dopa-induced dyskinesia (LID) in a 6-hydroxydopamine (6-OHDA)-lesioned mouse model of PD. Perindopril, captopril, and enalapril were used as ACEIs. The co-treatment of ACEI with L-dopa significantly decreased LID development in 6-OHDA-lesioned mice. In addition, the astrocyte and microglial transcripts involving Ccl2, C3, Cd44, and Iigp1 were reduced by co-treatment with ACEI and L-dopa in the 6-OHDA-lesioned striatum. In conclusion, co-treatment with ACEIs and L-dopa, such as perindopril, captopril, and enalapril, may mitigate the severity of L-DOPA-induced dyskinesia in a mouse model of PD.


Angiotensin-Converting Enzyme Inhibitors , Disease Models, Animal , Dyskinesia, Drug-Induced , Levodopa , Oxidopamine , Animals , Levodopa/adverse effects , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Mice , Dyskinesia, Drug-Induced/drug therapy , Dyskinesia, Drug-Induced/prevention & control , Male , Mice, Inbred C57BL , Captopril/pharmacology , Captopril/therapeutic use , Parkinson Disease/drug therapy , Perindopril/pharmacology , Perindopril/therapeutic use , Enalapril/pharmacology , Enalapril/therapeutic use , Astrocytes/drug effects , Astrocytes/metabolism , Microglia/drug effects , Microglia/metabolism , Antiparkinson Agents/pharmacology
2.
Front Microbiol ; 15: 1342098, 2024.
Article En | MEDLINE | ID: mdl-38633706

A novel Gram-negative, obligate anaerobe, non-motile, flagella-lacking, catalase- and oxidase-negative, coccobacilli-shaped bacterial strain designated AGMB02718T was isolated from swine feces. The 16S rRNA gene analysis indicated that strain AGMB02718T belonged to the genus Mesosutterella with the highest similarity to M. multiformis 4NBBH2T (= DSM 106860T) (sequence similarity of 96.2%), forming a distinct phylogenetic lineage. Its growth occurred at 25-45°C (optimal 37°C) and in 0.5-1% NaCl (optimal 0.5%). Strain AGMB02718T was asaccharolytic and contained menaquinone 6 (MK-6) and methylmenaquinone 6 (MMK-6) as the predominant respiratory quinones. The major cellular fatty acids in the isolate were C18:1ω9c and C16:0. Based on the whole-genome sequencing analysis, strain AGMB02718T had a 2,606,253 bp circular chromosome with a G + C content of 62.2%. The average nucleotide identity value between strain AGMB02718T and M. multiformis 4NBBH2T was 72.1%, while the digital DNA-DNA hybridization value was 20.9%. Interestingly, genome analysis suggested that strain AGMB02718T possessed a low-toxicity lipopolysaccharide (LPS) because the genome of the isolate does not include lpxJ and lpxM genes for Kdo2-Lipid A (KLA) assembly, which confers high toxicity to LPS. Moreover, in vitro macrophage stimulation assay confirmed that AGMB02718T produced LPS with low toxicity. Because the low-toxicity LPS produced by the Sutterellaceae family is involved in regulating host immunity and low-toxicity LPS-producing strains can help maintain host immune homeostasis, we evaluated the anti-inflammatory activity of strain AGMB02718T against inflammatory bowel disease (IBD). As a result, strain AGMB02718T was able to prevent the inflammatory response in a dextran sulfate sodium (DSS)-induced colitis model. Therefore, this strain represents a novel species of Mesosutterella that has a protective effect against DSS-induced colitis, and the proposed name is Mesosutterella faecium sp. nov. The type strain is AGMB02718T (=GDMCC 1.2717T = KCTC 25541T).

3.
Small ; : e2308317, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38564785

Proactive management of foodborne illness requires routine surveillance of foodborne pathogens, which requires developing simple, rapid, and sensitive detection methods. Here, a strategy is presented that enables the detection of multiple foodborne bacteria using a 3D nanostructure swab and deep learning-based Raman signal classification. The nanostructure swab efficiently captures foodborne pathogens, and the portable Raman instrument directly collects the Raman signals of captured bacteria. a deep learning algorithm has been demonstrated, 1D convolutional neural network with binary labeling, achieves superior performance in classifying individual bacterial species. This methodology has been extended to mixed bacterial populations, maintaining accuracy close to 100%. In addition, the gradient-weighted class activation mapping method is used to provide an investigation of the Raman bands for foodborne pathogens. For practical application, blind tests are conducted on contaminated kitchen utensils and foods. The proposed technique is validated by the successful detection of bacterial species from the contaminated surfaces. The use of a 3D nanostructure swab, portable Raman device, and deep learning-based classification provides a powerful tool for rapid identification (≈5 min) of foodborne bacterial species. The detection strategy shows significant potential for reliable food safety monitoring, making a meaningful contribution to public health and the food industry.

4.
Gut Liver ; 18(2): 257-264, 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38384180

Background/Aims: : Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases. This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers. Methods: : Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed. Results: : One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups. Conclusions: : Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.


Benzene Derivatives , Endoscopic Mucosal Resection , Imidazoles , Stomach Neoplasms , Stomach Ulcer , Humans , Esomeprazole/therapeutic use , Ulcer/drug therapy , Ulcer/etiology , Proton Pump Inhibitors/therapeutic use , Stomach Ulcer/drug therapy , Stomach Ulcer/surgery , Stomach Ulcer/etiology , Stomach Neoplasms/etiology , Endoscopic Mucosal Resection/adverse effects
5.
Toxicon ; 240: 107635, 2024 Mar.
Article En | MEDLINE | ID: mdl-38364981

The role of the inflammatory process in the pathogenesis of local edema-related envenomation has not been explored with endemic venomous snakebites in Korea. Gloydius species are responsible for most snakebites in South Korea. In this study we aimed to investigate whether the neutrophil-lymphocyte ratio is relevant to snake envenomation-induced local edema in South Korea. This retrospective study divided 126 patients into two groups according to local edema severity at presentation. Logistic regression models were used to investigate the association between the neutrophil-lymphocyte ratio and local edema. Sixty-one (48.4%) patients had grade 2 or higher local edema at presentation despite 21 of them being given antivenom before presentation. During hospitalization, local edema progressed in 61 patients 48 (11.5-48) hours after presentation, and 54 patients demonstrated grade 3 or higher local edema. A higher neutrophil-lymphocyte ratio at presentation after adjustment for factors related to envenomation and antivenom administration and factors influencing the neutrophil-lymphocyte ratio were associated with both a higher grade of local edema at presentation and a higher peak local edema grade during hospitalization. The delta neutrophil-lymphocyte ratio during the first 24 h after presentation was related to the local edema progression after presentation. The neutrophil-lymphocyte ratio at presentation is associated with the severity of local edema-related envenomation. Furthermore, the change in the neutrophil-lymphocyte ratio during the first 24 h is related to the risk of local edema progression. Further clinical and experimental research aimed at investigating the role of inflammation on the pathogenesis of local edema should be conducted. This study may suggest the introduction of short-term anti-inflammatory agents considering the failure of antivenom to curb local edema.


Snake Bites , Animals , Humans , Snake Bites/epidemiology , Antivenins/therapeutic use , Neutrophils , Retrospective Studies , Edema/chemically induced , Republic of Korea/epidemiology , Lymphocytes
6.
Cornea ; 43(4): 531-533, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38166178

PURPOSE: The aim of this study was to present the surgical management of a patient with ocular copper deposition associated with monoclonal gammopathy of undetermined significance (MGUS). METHODS: This is a case report of a 44-year-old man with MGUS who presented to us with bilateral diffuse deposition of copper in the cornea and lens. RESULTS: Despite initiating systemic therapy for MGUS, no corneal clearing was observed. A decision was made to proceed with cataract extraction in the left eye given worsening vision. Despite trypan blue staining and a central descemetorhexis, visualization remained too poor to complete phacoemulsification. Pars plana lensectomy and vitrectomy to remove the residual lens material and placement of a posterior chamber intraocular lens in the sulcus with endoillumination was subsequently performed. As vision in the left eye steadily improved postoperatively, cataract surgery was then performed in the right eye. With use of trypan blue, creation of a 6-mm central descemetorhexis, and a retinal light pipe for endoillumination anteriorly to augment visualization, capsulorhexis, phacoemulsification, and insertion of intraocular lens in the bag were completed without difficulty. The patient's vision improved at subsequent follow-ups, reaching a final best-corrected visual acuity of 20/20-1 in the right eye and 20/25-1 in the left eye. CONCLUSIONS: Ocular copper deposition is a rare manifestation of MGUS. Cataract extraction is challenging, often requiring advanced techniques. Endoillumination is useful to improve visualization through the dense corneal copper deposition.


Cataract , Monoclonal Gammopathy of Undetermined Significance , Phacoemulsification , Male , Humans , Adult , Copper , Cataract/complications , Monoclonal Gammopathy of Undetermined Significance/complications , Trypan Blue , Visual Acuity , Phacoemulsification/methods , Vitrectomy/methods
7.
Food Sci Biotechnol ; 33(1): 171-180, 2024 Jan.
Article En | MEDLINE | ID: mdl-38186621

Following 3R (reduction, refinement, and replacement) principles, we employed the rat liver S9 fraction to mimic liver metabolism of curcumol having high in vitro IC50 on cancer cells. In HCT116 and HT29 colon cancer cells, the metabolites of curcumol by S9 fraction exerted more enhanced activity in inducing cell cycle arrest and apoptosis via regulating the expression of cyclin D1, CDK1, p21, PARP and Bcl-2 than curcumol. In addition, oral administration of curcumol at 4 mg/kg BW significantly suppressed the development of colon tumor induced by azoxymethane/dextran sulfate sodium, and induced cell cycle arrest and apoptosis in tumor tissues. In mass analysis, curcumenol and curzerene were identified as the metabolites of curcumol by S9 fraction metabolism. Taken together, curcumol metabolites showed the enhanced suppressive effect on colon cancer, suggesting that S9 fraction can be considered as simple, fast, and bio-mimicking platform for the screening of chemical libraries on different chronic diseases.

8.
Science ; 383(6678): 70-76, 2024 Jan 05.
Article En | MEDLINE | ID: mdl-38175890

Block copolymer self-assembly affords diverse nanostructures, spanning from spheres and cylinders to networks, offering meticulous control over properties and functionalities at the nanoscale. However, creating thermodynamically stable network structures with high packing frustration remains a challenge. In this study, we report a methodology to access diverse network structures such as gyroid, diamond, and primitive phases from diblock copolymers using end group and linker chemistry. The stability of the medial packing of polymer chain ends (plumber's nightmare structure) over skeletal aggregation (gyroid) is attributed to the interplay between the strength of the end-end interactions and the initial shape of the curvature. Our study establishes an approach to develop tailored network structures from block copolymers, providing an important platform for using block copolymers in nanotechnology applications.

9.
Food Sci Biotechnol ; 33(3): 711-720, 2024 Feb.
Article En | MEDLINE | ID: mdl-38274180

In this study, we investigated the effect of cycloastragenol (CAG), a triterpenoid isolated from Astragalus membranaceus roots, on regulating the adipogenesis and fat accumulation in vitro and in vivo. During the adipogenesis of 3T3-L1 cells, CAG inhibited lipid accumulation and the expression of key adipogenic factors, proliferator-activated receptor γ (PPARγ) and CCAAT enhancer binding protein α (C/EBPα) and increased the expression of Gli1, a key mediator in Hedgehog (Hh) signaling. In HFD-induced animal experiment, CAG significantly reduced body weight gain without affecting brown fat weight. In addition, CAG regulated the expression of PPARγ, C/EBPα, and Gli1 in visceral white adipose tissue (vWAT). We also confirmed the inhibitory effect of CAG on specifically targeting white adipose tissue (WAT) formation in stromal vascular fraction (SVF) cell differentiation. Taken together, these results suggest that CAG may be a potent phytochemical preventing adipogenesis and obesity via Hh signaling. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01403-0.

11.
Ann Surg Oncol ; 31(2): 735-743, 2024 Feb.
Article En | MEDLINE | ID: mdl-37952018

BACKGROUND: Intraperitoneal chemotherapy is promising for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of intraperitoneal paclitaxel combined with S-1 and intravenous paclitaxel, the sensitivity analysis suggested clinical efficacy. Thus, attempts to combine intraperitoneal paclitaxel with other systemic therapies with higher efficacy have been warranted. We sought to explore the efficacy of intraperitoneal paclitaxel with S-1 and cisplatin. PATIENTS AND METHODS: Gastric cancer patients with peritoneal metastasis were enrolled in the phase II trial. In addition to the established S-1 and cisplatin regimen every 5 weeks, intraperitoneal paclitaxel was administered on days 1, 8, and 22 at a dose of 20 mg/m2. The primary endpoint was overall survival rate at 1 year after treatment initiation. Secondary endpoints were progression-free survival and toxicity. RESULTS: Fifty-three patients were enrolled and fully evaluated for efficacy and toxicity. The 1-year overall survival rate was 73.6% (95% confidence interval 59.5-83.4%), and the primary endpoint was met. The median survival time was 19.4 months (95% confidence interval, 16.1-24.6 months). The 1-year progression-free survival rate was 49.6% (95% confidence interval, 34.6-62.9%). The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (25%), anemia (30%), diarrhea (13%), and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in four patients. There was one treatment-related death. CONCLUSIONS: Intraperitoneal paclitaxel combined with S-1 and cisplatin is well tolerated and active in gastric cancer patients with peritoneal metastasis.


Peritoneal Neoplasms , Stomach Neoplasms , Humans , Cisplatin , Stomach Neoplasms/pathology , Paclitaxel , Peritoneal Neoplasms/secondary , Antineoplastic Combined Chemotherapy Protocols
12.
Materials (Basel) ; 16(23)2023 Nov 22.
Article En | MEDLINE | ID: mdl-38068019

Wire bonding, one of the methods for electrically connecting a semiconductor chip with a substrate, involves attaching thin metal wires to pads. It is the oldest electrical connection method that exhibits high compatibility with other processes. The metal wires used for electrical connection in wire bonding are mainly made of Au, Cu, and Ag. After the wire bonding, molding is performed using the epoxy molding compound (EMC). However, EMC inevitably contains ions such as halogen elements. In addition, it absorbs moisture due to its hydrophilicity, creating a corrosive environment with electrolytes. In this study, we evaluated the influence of hydrochloric acid concentration on corrosion behavior between Au or Cu bonding wires and sputtered Al bond pads. The electrochemical factors such as corrosion potential difference (ΔE), galvanic corrosion current density (ig), and anodic and cathodic Tafel slopes were found to influence galvanic corrosion behavior. Galvanic corrosion tendency in first bond and second bond areas of PCB unit specimen was confirmed.

13.
Arch Microbiol ; 206(1): 19, 2023 Dec 12.
Article En | MEDLINE | ID: mdl-38086977

Obesity is a global health threat that causes various complications such as type 2 diabetes and nonalcoholic fatty liver disease. Gut microbiota is closely related to obesity. In particular, a higher Firmicutes to Bacteroidetes ratio has been reported as a biomarker of obesity, suggesting that the phylum Bacteroidetes may play a role in inhibiting obesity. Indeed, the genus Bacteroides was enriched in the healthy subjects based on metagenome analysis. In this study, we determined the effects of Bacteroides stercoris KGMB02265, a species belonging to the phylum Bacteroidetes, on obesity both in vitro and in vivo. The cell-free supernatant of B. stercoris KGMB02265 inhibited lipid accumulation in 3T3-L1 preadipocytes, in which the expression of adipogenic marker genes was repressed. In vivo study showed that the oral administration of B. stercoris KGMB02265 substantially reduced body weight and fat weight in high-fat diet induced obesity in mice. Furthermore, obese mice orally administered with B. stercoris KGMB02265 restored glucose sensitivity and reduced leptin and triglyceride levels. Taken together, our study reveals that B. stercoris KGMB02265 has anti-obesity activity and suggests that it may be a promising candidate for treating obesity.


Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Humans , Mice , Animals , Diabetes Mellitus, Type 2/complications , Obesity , Bacteroides/genetics , Mice, Inbred C57BL
14.
BMC Gastroenterol ; 23(1): 447, 2023 Dec 18.
Article En | MEDLINE | ID: mdl-38110901

BACKGROUND: Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE). METHODS: We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups. RESULTS: By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups. CONCLUSIONS: The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD. TRIAL REGISTRATION: NCT04080726 ( https://classic. CLINICALTRIALS: gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.


Esophagitis, Peptic , Esophagitis , Gastroesophageal Reflux , Peptic Ulcer , Humans , Double-Blind Method , Esomeprazole/adverse effects , Esophagitis, Peptic/drug therapy , Gastroesophageal Reflux/drug therapy , Gastroesophageal Reflux/diagnosis , Proton Pump Inhibitors/adverse effects , Treatment Outcome
15.
Heliyon ; 9(12): e22728, 2023 Dec.
Article En | MEDLINE | ID: mdl-38107318

Background: Extracorporeal membrane oxygenation (ECMO) patients have a high incidence of acute kidney injury (AKI). Extracorporeal cardiopulmonary resuscitation (ECPR) patients are more likely to develop AKI than ECMO patients because of serious injury during cardiac arrest (CA). Objectives: This study aims to assess the occurrence and outcomes of AKI in ECPR and ECMO, and to identify specific risk factors and clinical implications of AKI in ECPR. Methods: This is a retrospective observational study from a single tertiary care hospital in Gwangju, Korea. Adults (≥18 years) who received ECMO with cardiac etiology in the emergency and inpatient departments from January 2015 to December 2021 were included. The patients (n = 169) were divided into two groups, ECPR and ECMO without CA, and the occurrence of AKI was investigated. The primary outcome of the study was in-hospital mortality, and the secondary outcomes were six-month cerebral performance category (CPC) and AKI during hospitalization. Results: The incidence of AKI was significantly higher with ECPR (67.5 %) than with ECMO without CA (38.4 %). ECPR was statistically significant for Expire (adjusted OR (aOR) 2.45, 95 % CI 1.28-4.66) and Poor CPC (2.59, 1.32-5.09). AKI was also statistically significant for Expire (6.69, 3.37-13.29) and Poor CPC (5.45, 2.73-10.88). AKI was the determining factor for the outcomes of ECPR (p = 0.01). Conclusions: ECPR patients are more likely to develop AKI than ECMO without CA patients. In ECPR patients, AKI leads to poor outcomes. Therefore, clinicians should be careful not to develop AKI in ECPR patients.

16.
Nat Commun ; 14(1): 7504, 2023 11 18.
Article En | MEDLINE | ID: mdl-37980404

Nucleic acid detection powered by CRISPR technology provides a rapid, sensitive, and deployable approach to molecular diagnostics. While exciting, there remain challenges limiting its practical applications, such as the need for pre-amplification and the lack of quantitative ability. Here, we develop an asymmetric CRISPR assay for cascade signal amplification detection of nucleic acids by leveraging the asymmetric trans-cleavage behavior of competitive crRNA. We discover that the competitive reaction between a full-sized crRNA and split crRNA for CRISPR-Cas12a can induce cascade signal amplification, significantly improving the target detection signal. In addition, we find that CRISPR-Cas12a can recognize fragmented RNA/DNA targets, enabling direct RNA detection by Cas12a. Based on these findings, we apply our asymmetric CRISPR assay to quantitatively detect microRNA without the need for pre-amplification, achieving a detection sensitivity of 856 aM. Moreover, using this method, we analyze and quantify miR-19a biomarker in plasma samples from bladder cancer patients. This asymmetric CRISPR assay has the potential to be widely applied for simple and sensitive nucleic acid detection in various diagnostic settings.


MicroRNAs , Nucleic Acids , Humans , RNA, Guide, CRISPR-Cas Systems , MicroRNAs/genetics , Biological Assay , Technology , CRISPR-Cas Systems/genetics , Nucleic Acid Amplification Techniques
17.
J Chem Phys ; 159(17)2023 Nov 07.
Article En | MEDLINE | ID: mdl-37921254

We present a strategic approach for enhancing the ionic conductivity of block copolymer electrolytes. This was achieved by introducing mixed ionic liquids (ILs) with varying molar ratios, wherein the imidazolium cation was paired with either tetrafluoroborate (BF4) anion or bis(trifluoromethylsulfonyl)imide (TFSI) anion. Two polymer matrices, poly(4-styrenesulfonate)-b-polymethylbutylene (SSMB) and poly(4-styrenesulfonyl (trifluoromethanesulfonyl)imide)-b-polymethylbutylene (STMB), were synthesized for this purpose. All the SSMB and STMB containing mixed ILs showed hexagonal cylindrical structures, but the type of tethered acid group significantly influenced the interfacial properties. STMB electrolytes demonstrated enhanced segregation strength, which was attributed to strengthened Coulomb and hydrogen bonding interactions in the ionic domains, where the ILs were uniformly distributed. In contrast, the SSMB electrolytes exhibited increased concentration fluctuations because the BF4 anions were selectively sequestered at the block interfaces. This resulted in the effective confinement of imidazolium TFSI along the ionic domains, thereby preventing ion trapping in dead zones and facilitating rapid ion diffusion. Consequently, the SSMB electrolytes with mixed ILs demonstrated significantly improved ionic conductivities, surpassing the expected values based on the arithmetic average of the conductivities of each IL, whereas the ionic conductivity of the STMB was aligned with the expected average. The methodology explored in this study holds great promise for the development of solid-state polymer electrolytes.

18.
Biochimie ; 2023 Nov 04.
Article En | MEDLINE | ID: mdl-37931793

Mesenchymal stem cells (MSCs) have potential as a viable treatment option in the field of regenerative medicine, but MSC-based therapy needs to be more efficient. Preconditioning is a method to improve MSC-based therapy, and dimethyl fumarate (DMF) - an agent that can enhance the antioxidative capacity of cells - can be considered for preconditioning of MSCs. In this study, we treated bone marrow-derived MSCs with DMF and evaluated their proteome using bottom-up proteomics. The MSCs were exposed to 10 µM DMF for 24 h, followed by lysis with an SDS solution, digestion with trypsin using an s-trap column, and analysis using nanoLC-MS/MS, which identified 2262 proteins with confidence. Bioinformatic analysis of the identified proteins revealed 47 upregulated proteins and 81 downregulated proteins upon DMF treatment. Pathway enrichment analysis suggested a possible decrease in autophagy and a decrease in the activity of the TCA cycle, while indicating a potential increase in proliferation and antioxidant activity in DMF-treated MSCs compared to untreated MSCs. Our findings suggest that DMF can enhance the proliferation of MSCs and increase their stability, and that preconditioning could improve the therapeutic efficacy of MSCs for the treatment of regenerative diseases.

19.
Nucleic Acids Res ; 51(20): 11178-11196, 2023 11 10.
Article En | MEDLINE | ID: mdl-37850636

Von Hippel-Lindau (VHL) is a tumor suppressor that functions as the substrate recognition subunit of the CRL2VHL E3 complex. While substrates of VHL have been identified, its tumor suppressive role remains to be fully understood. For further determination of VHL substrates, we analyzed the physical interactome of VHL and identified the histone H3K9 methyltransferase SETBD1 as a novel target. SETDB1 undergoes oxygen-dependent hydroxylation by prolyl hydroxylase domain proteins and the CRL2VHL complex recognizes hydroxylated SETDB1 for ubiquitin-mediated degradation. Under hypoxic conditions, SETDB1 accumulates by escaping CRL2VHL activity. Loss of SETDB1 in hypoxia compared with that in normoxia escalates the production of transposable element-derived double-stranded RNAs, thereby hyperactivating the immune-inflammatory response. In addition, strong derepression of TEs in hypoxic cells lacking SETDB1 triggers DNA damage-induced death. Our collective results support a molecular mechanism of oxygen-dependent SETDB1 degradation by the CRL2VHL E3 complex and reveal a role of SETDB1 in genome stability under hypoxia.


Genomic Instability , Histone-Lysine N-Methyltransferase , Hypoxia , Humans , Genes, Tumor Suppressor , Histone-Lysine N-Methyltransferase/metabolism , Hypoxia/genetics , Hypoxia/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Oxygen/metabolism , Ubiquitin-Protein Ligases/genetics , Von Hippel-Lindau Tumor Suppressor Protein/genetics , Von Hippel-Lindau Tumor Suppressor Protein/metabolism
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