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1.
Ann Occup Environ Med ; 36(0): e25, 2024.
Article in English | MEDLINE | ID: mdl-39238397

ABSTRACT

BACKGROUND: The rise in single-person households is a global phenomenon with well-documented implications for both physical and mental well-being. However, there remains a scarcity of studies focusing specifically on the health impacts of single-person households on workers. This study aims to address this gap by comparing insomnia symptoms between single- and multi-person household workers, shedding light on the health implications of household composition. METHODS: This study utilized data from the Sixth Korean Working Conditions Survey. Insomnia symptoms were categorized into normal sleep and insomnia symptom groups utilizing the 3-item Minimal Insomnia Symptom Scale. Multiple logistic regression analysis was employed to examine the association between single-person household wage workers and insomnia symptoms. RESULTS: In comparison to wage workers from multi-person households, those from single-person households exhibited heightened risks of reporting insomnia symptoms. In the fully adjusted model, the odds ratios for symptoms of insomnia among single-person household wage workers was 1.173 (95% confidence interval: 1.020-1.349). CONCLUSIONS: This study underscores that single-person household wage workers in Korea face an elevated risk of insomnia symptoms compared to their counterparts in multi-person households.

2.
Int J Food Microbiol ; 425: 110897, 2024 Dec 02.
Article in English | MEDLINE | ID: mdl-39241349

ABSTRACT

Lactic acid bacteria are commonly used in plant-based fermentation to reduce off-flavor and improve sensory characteristics. However, there have been few studies on Latilactobacillus sakei for plant-based yogurt fermentation and, particularly, its metabolic features at the genomic level remain unclear. This study aims to analyze the fermentation characteristics of the L. sakei DCF0720 strain and compare genetics and metabolic relations. For this, DCF0720 was used to ferment the black soybean milk and conduct the physicochemical analysis and sensory test. The genomic and metabolic analyses were performed by complete genome sequencing and 500 MHz 1H NMR, respectively. As a result, DCF0720 exhibited enhanced fermentation performance and sensory evaluations at 37 °C compared to 30 °C, which is generally recognized as the optimal growth temperature for most L. sakei strains. It also produced flavor enhancing volatile compounds such as acetoin and hydroxyacetone, possessing all three key genes for acetoin biosynthesis. DCF0720 lacks 2,3-butanediol dehydrogenase, which leads to the inhibition of acetoin production. DCF0720 possesses a complete pathway to utilize primary black soybean carbon sources such as sucrose, raffinose, and stachyose. DCF0720 also possesses genes for the GH28 family, including the key enzymes in the hydrolysis of pectin substances, which means eliminating the main soybean nonstarch polysaccharides. This study demonstrates that DCF0720 is a suitable starter for plant-based yogurt fermentation, providing a better understanding of fermentation conditions with genetic and metabolic features for black soybean yogurt. Various carbon source utilization abilities with depth metabolic pathway analysis provide that DCF0720 can be employed to develop enhanced starter cultures for black soybean yogurt and diverse plant-based yogurts.


Subject(s)
Fermentation , Glycine max , Latilactobacillus sakei , Yogurt , Yogurt/microbiology , Latilactobacillus sakei/metabolism , Latilactobacillus sakei/genetics , Metabolomics , Taste , Genomics , Genome, Bacterial , Food Microbiology , Acetoin/metabolism , Flavoring Agents/metabolism , Soy Milk/metabolism
3.
Sci Prog ; 107(3): 368504241276768, 2024.
Article in English | MEDLINE | ID: mdl-39248181

ABSTRACT

OBJECTIVES: Injection laryngoplasty (IL) has been widely used as an initial treatment option for unilateral vocal fold paralysis (UVFP). An additional (second) IL is considered a salvage treatment for unsatisfactory outcomes of initial IL resulting from inadequate injection or early resorption of the injection material. This study aims to evaluate the efficacy of additional IL, distinguishing between "salvage" (within 4 months) and "repeated" injections (beyond 4 months), and to analyze prognostic factors for successful outcomes. METHODS: This retrospective study involved patients who received IL at Asan Medical Center from January 2014 to December 2020. Voice parameters were collected after each procedure, and those who conducted the statistical analysis were blinded to the study subjects. Among the 65 patients who underwent additional IL, 51 patients were enrolled in this study. Postinjection grade, roughness, breathiness, asthenia, strain (GRBAS) scales were used to determine satisfactory treatment outcomes. Success of the additional IL was defined as a postinjection grade of dysphonia score of 0 or 1, with a reduction in grade compared with the preinjection grade. RESULTS: The mean age of the patients was 61.6 years. Out of a total of 51 patients, 37 were men participating in the study. The odds ratio represents the likelihood of success in the second IL. Improved voice outcome after the additional IL was maintained in 23 (45%) patients. Compared with the failure group, the success group had a longer injection time interval between the initial and additional injection (9.1 vs. 7.4 months, respectively, p = 0.010). The success group had a higher proportion of patients with injection intervals >6 months (73.9% vs. 42.9%, p = 0.026). Logistic regression analysis revealed an injection interval >6 months had an odds ratio of 0.265 (confidence interval: 0.080-0.874, p = 0.029). CONCLUSIONS: Additional injections would benefit the patients whose voice outcomes are maintained for a longer period (>6 months) after the first injection.


Subject(s)
Laryngoplasty , Salvage Therapy , Vocal Cord Paralysis , Humans , Vocal Cord Paralysis/surgery , Vocal Cord Paralysis/physiopathology , Vocal Cord Paralysis/therapy , Male , Laryngoplasty/methods , Middle Aged , Female , Retrospective Studies , Salvage Therapy/methods , Treatment Outcome , Aged , Injections , Adult , Voice Quality
4.
Integr Med Res ; 13(3): 101065, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39224580

ABSTRACT

Background: Although several studies have reported the effectiveness of acupuncture treatment for adhesive capsulitis (AC), research on pharmacopuncture therapy for AC remains limited. We compared the effectiveness and safety of pharmacopuncture and physiotherapy for AC. Methods: This pragmatic, randomized, controlled, parallel-group pilot study enrolled patients with limitations of shoulder movement and a numeric rating scale (NRS) score for shoulder pain ≥5 randomized (1:1) to the pharmacopuncture therapy (PPT) and physiotherapy (PT) groups. Treatment sessions were administered twice weekly for 6 weeks, and the participants were followed up for 13 weeks after randomization. The primary outcome was the NRS score for shoulder pain, and the secondary outcomes were the visual analog scale (VAS), Shoulder Pain and Disability Index (SPADI), range of motion (ROM), patient global impression of change (PGIC), EuroQol 5-Dimension 5-Level (EQ-5D-5L), and Short Form 12 Health Survey (SF-12) scores. The intention-to-treat (ITT) analysis was set as the primary analysis. Results: Among 50 participants, for the primary endpoint (week 7) the PPT group showed a significantly superior improvement in NRS, VAS, SPADI, ROM for flexion, ROM for abduction, and EQ-5D-5L scores. The ROM for extension, ROM for adduction, physical component summary, and patient global impression of change were significantly better in the PPT than in the PT group, and these effects were sustained until week 13. Conclusion: In this pilot study, PPT showed better effects than PT, confirming the feasibility of a follow-up main study. Trial registration: Clinicaltrials.gov (NCT05292482) and cris.nih.go.kr (KCT0007198).

6.
Article in English | MEDLINE | ID: mdl-39115573

ABSTRACT

PURPOSE: Laryngopharyngeal reflux disease (LPRD) is mainly treated with proton pump inhibitors (PPI) such as esomeprazole, which have shortcomings like delayed absorption and increased osteoporosis. Fexuprazan is a novel potent potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset and long duration of action. To assess the efficacy and safety of fexuprazan compared to esomeprazole in patients with LPRD. METHODS: This prospective, randomized, double-blinded, multicenter, active-controlled trial was conducted in nine otolaryngologic clinics. Patients with reflux symptom index (RSI) ≥ 13 and reflux finding score (RFS) ≥ 7 were randomly assigned to the fexuprazan or esomeprazole groups, and received fexuprazan 40-mg or esomeprazole 40-mg once daily for 8 weeks. The outcomes were (1) mean change, change rate, and valid rate in RSI, RFS, and LPR-related questionnaires; and (2) adverse events. RESULTS: A total of 136 patients (fexuprazan n = 68, esomeprazole n = 68) were followed up for ≥ 1 month. Each parameter significantly improved after 4 and 8 weeks in each group, with no significant differences between the two groups. For those with severe symptoms (RSI ≥ 18), the fexuprazan group (n = 32) showed more improvement in the mean change and change rate in the RSI than esomeprazole group (n = 31) after 4 weeks (p = .036 and .045, respectively). This phenomenon was especially observed in hoarseness and troublesome cough. CONCLUSION: Fexuprazan improved symptoms and signs without no serious adverse events in patients with LPRD. In patients with severe symptoms, fexuprazan resulted in a faster symptom improvement than PPI. TRIAL REGISTRATION: KCT0007251, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22100 .

7.
Biology (Basel) ; 13(8)2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39194540

ABSTRACT

Intervertebral disc degeneration (IDD) progresses owing to damage and depletion of nucleus pulposus (NP) cells. Cytoprotection mitigates oxidative stress, nutrient deprivation, and mechanical stress, which lead to cell damage and necrosis. We aimed to examine the protective effect of Raphanus sativus Linne (RSL), common radish, against oxidative stress by H2O2 in human NP cells and whether the RSL extracts can inhibit triggering receptor expressed on myeloid cells 2 (TREM2), an inducer of apoptosis and degeneration in NP cells. We administered hydrogen peroxide (H2O2) to cultured human NP cells treated with RSL extracts. We used immunoblotting and quantitative PCR to investigate expression of the apoptosis-associated proteins in cultured cells. RSL significantly enhanced cell survival by suppressing the activation of cleaved caspase-3 and Bax. In contrast, RSL extract increased Bcl2 concentration to downregulate apoptosis. Additionally, RSL treatment notably enhanced the mRNA levels of ACAN and Col2a1 while significantly reducing those of ADAMTS-4, ADAMTS-5, MMP3, and MMP13, key genes involved in NP degeneration. While H2O2 elevated TREM2 expression, causing disc degeneration, RSL downregulated TREM2 expression. Thus, our findings imply that RSL supports human NP cells under oxidative stress and regulates the pathways underlying disc degeneration, particularly TREM2, and that RSL extracts may potentially prevent IDD.

8.
Medicine (Baltimore) ; 103(32): e39183, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39121270

ABSTRACT

The use of integrative Korean medicine treatment (IKMT) for patients with knee osteoarthritis (OA) has been reported previously; however, to date, no studies have investigated the long-term prognosis of these patients following IKMT for primary knee OA. We aimed to examine the long-term effects of IKMT in patients diagnosed with primary knee OA and receiving IKMT during hospitalization. This retrospective observational study, complemented by a follow-up survey, included patients with primary knee OA who received IKMT during hospitalization across 7 Korean medicine hospitals. The primary outcome was the Numerical Rating Scale knee-pain score, whereas the secondary outcomes were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQol-5 dimension-5 level questionnaire (EQ-5D-5L), and Patient Global Impression of Change scores. Patients were evaluated at admission, discharge, and during follow-up. Of the 180 included patients, 81 responded to the survey. Compared with the corresponding values at admission, the Numerical Rating Scale score decreased by 2.44 (2.08-2.81) points at discharge and 1.89 (1.5-2.26) points at follow-up. Additionally, compared with their scores at admission, the WOMAC score decreased by 17.20 (13.68-20.71) points at discharge and 25.74 (22.22-29.26) points at follow-up, whereas the EuroQol-5 dimension-5 level questionnaire score improved by -0.15 (-0.18 to -0.12) points at discharge and -0.12 (-0.15 to -0.09) points at follow-up. The patients expressed high satisfaction with pharmacopuncture (65.4%), acupuncture (54.03%), physical therapy (35.8%), and herbal medicine (34.6%). Regarding Patient Global Impression of Change, 96.30% of the patients reported improvement. IKMT was effective in improving pain, functional disability, and quality of life in patients with primary knee OA. Its effects were maintained throughout the long-term follow-up period, and physical functions continuously improved.


Subject(s)
Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/therapy , Female , Male , Retrospective Studies , Middle Aged , Aged , Republic of Korea , Medicine, Korean Traditional , Treatment Outcome , Integrative Medicine/methods , Pain Measurement , Quality of Life , Inpatients/statistics & numerical data
9.
Am J Cardiol ; 229: 56-62, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39122204

ABSTRACT

Although the adverse effects of long-term use of vitamin K oral anticoagulant (OAC), warfarin, on the coronary vasculature are well-established, it remains unknown whether nonvitamin K oral anticoagulants play a role in the attenuation of plaque progression and coronary calcification. This study aimed to compare the changes in atherosclerotic plaques and calcification of the coronary arteries in patients with atrial fibrillation (AF) treated with edoxaban and warfarin. A total of 150 OAC-naïve patients with AF and atherosclerotic lesions on coronary computed tomography angiography (CCTA) were enrolled and randomly assigned to the edoxaban or warfarin treatment groups. All enrolled patients received rosuvastatin 10 mg and 119 patients completed the entire study protocol. A total of 12 months after the assigned OAC treatment, follow-up CCTA was performed and changes in plaque and calcium volumes of the coronary arteries were analyzed. The baseline characteristics of the 2 groups were well-balanced. The percentage of time in therapeutic range in the warfarin group was 61.1%. Compared with the baseline CCTA, there was a significant reduction in plaque volume after 12 months of OAC and rosuvastatin administration in both groups, and the extent of regression did not differ significantly between the groups. The increase in calcium volume was greater in the warfarin group than in the edoxaban group; however, the difference was not significant. In OAC-naïve patients with AF and atherosclerotic coronary lesions who were treated with moderate-intensity statin, edoxaban use did not have a positive effect on atherosclerotic plaques and coronary calcification compared with warfarin use over a 12-month follow-up period.

10.
Materials (Basel) ; 17(16)2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39203284

ABSTRACT

Lithium-ion batteries are superior energy storage devices that are widely utilized in various fields, from electric cars to small portable electric devices. However, their susceptibility to thermal runaway necessitates improvements in battery case materials to improve their safety. This study used electrochemical analyses, including open-circuit potential (OCP), potentiodynamic polarization, and critical pitting temperature (CPT) analyses, to investigate the corrosion resistance of super duplex stainless steel (SAF 2507) applied to battery cases in relation to post-weld heat treatment (PWHT) time. The microstructure during the manufacture, laser welding, and PWHT was analyzed using field-emission scanning electron microscopy, X-ray diffraction, and electron backscatter diffraction, and the chemical composition was analyzed using dispersive X-ray spectroscopy and electron probe micro-analysis. The PWHT increased the volume fraction of austenite from 5% to 50% over 3 min at 1200 °C; this increased the OCP from -0.21 V to +0.03 V, and increased the CPT from 56 °C to 73 °C. The PWHT effectively improved the corrosion resistance, laying the groundwork for utilizing SAF 2507 in battery case materials. But the alloy segregation and heterogeneous grain morphology after PWHT needs improvement.

11.
Nutrients ; 16(16)2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39203748

ABSTRACT

Insomnia is a common sleep disorder with significant societal and economic impacts. Current pharmacotherapies for insomnia are often accompanied by side effects, necessitating the development of new therapeutic drugs. In this study, the hypnotic effects and mechanisms of Sedum kamtschaticum 30% ethanol extract (ESK) and one of its active compounds, myricitrin, were investigated using pentobarbital-induced sleep experiments, immunohistochemistry (IHC), receptor binding assays, and enzyme-linked immunosorbent assay (ELISA). The pentobarbital-induced sleep experiments revealed that ESK and myricitrin reduced sleep latency and prolonged total sleep time in a dose-dependent manner. Based on c-Fos immunostaining, ESK, and myricitrin enhanced the GABAergic neural activity in sleep-promoting ventrolateral preoptic nucleus (VLPO) GABAergic. By measuring the level of GABA released from VLPO GABAergic neurons, ESK and myricitrin were found to increase GABA release in the hypothalamus. These effects were significantly inhibited by SCH. Moreover, ESK exhibited a concentration-dependent binding affinity for the adenosine A2A receptors (A2AR). In conclusion, ESK and myricitrin have hypnotic effects, and their underlying mechanisms may be related to the activation of A2AR.


Subject(s)
Hypnotics and Sedatives , Plant Extracts , Receptor, Adenosine A2A , Animals , Receptor, Adenosine A2A/metabolism , Hypnotics and Sedatives/pharmacology , Mice , Male , Plant Extracts/pharmacology , Sleep/drug effects , Sleep Initiation and Maintenance Disorders/drug therapy , Pentobarbital/pharmacology , GABAergic Neurons/drug effects , GABAergic Neurons/metabolism , gamma-Aminobutyric Acid/metabolism , Flavonoids/pharmacology , Preoptic Area/drug effects , Preoptic Area/metabolism
12.
J Neurochem ; 2024 Aug 25.
Article in English | MEDLINE | ID: mdl-39183510

ABSTRACT

Epidermal growth factor (EGF) is known to be a critical stimulant for inducing the proliferation of glioma cancer cells. In our study, we observed that GST-RhoA binds to pyruvate kinase M2 (PKM2) in vitro. While EGF reduced the levels of RhoA protein, it significantly increased p-Y42 RhoA, as well as PKM1 and PKM2 in LN18 glioma cell line. We determined that RhoA undergoes degradation through ubiquitination involving SCF1 and Smurf1. Interestingly, we observed that p-Y42 RhoA binds to PKM2, while the dephosphomimetic form, RhoA Y42F, did not. Additionally, our observation revealed that PKM2 stabilized both RhoA and p-Y42 RhoA. Importantly, RhoA, p-Y42 RhoA, and PKM2, but not RhoA-GTP, were localized in the nucleus upon EGF stimulation. Knockdown of RhoA with siRNA resulted in the reduced levels of phosphoglycerate kinase1 (PGK1) and microtubule affinity-regulating kinase 4 (MARK). Furthermore, we found that the promoter of PGK1 was associated with ß-catenin and YAP. Notably, p-Y42 RhoA and PKM2 co-immunoprecipitated with ß-catenin and YAP. Based on these findings, we proposed a novel mechanism by which p-Y42 RhoA and PKM2, in conjunction with ß-catenin and YAP, regulate PGK1 expression, contributing to the progression of glioma upon EGF.

13.
Nat Commun ; 15(1): 6803, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39122743

ABSTRACT

Preclinical studies are crucial for developing amyotrophic lateral sclerosis drugs. Current FDA-approved drugs have been created by monitoring limb muscle function and histological analysis of amyotrophic lateral sclerosis model animals. Drug candidates for this disease have yet to be tested for bulbar-onset type due to the limitations of traditional preclinical tools: excessive animal use and discrete detection of disease progress. Here, our study introduces an all-in-one, wireless, integrated wearable system for facilitating continuous drug efficacy assessment of dysphagia-related muscles in animals during natural eating behaviors. By incorporating a kirigami-based strain-isolation mechanism, this device mounted on the skin of animals mitigates electromyography signal contamination caused by unpredictable animal movements. Our findings indicate this system, measuring the progression of motor neuron denervation, offers high precision in monitoring drug effects on dysphagia-responsible bulbar muscles. This study paves the way for more humane and efficient approaches to developing treatment solutions for degenerative neuromuscular diseases.


Subject(s)
Amyotrophic Lateral Sclerosis , Disease Models, Animal , Electromyography , Wearable Electronic Devices , Amyotrophic Lateral Sclerosis/physiopathology , Amyotrophic Lateral Sclerosis/drug therapy , Animals , Electromyography/methods , Drug Evaluation, Preclinical , Deglutition Disorders/physiopathology , Deglutition Disorders/etiology , Muscle, Skeletal/drug effects , Muscle, Skeletal/physiopathology , Muscle, Skeletal/innervation , Humans , Male , Motor Neurons/drug effects , Motor Neurons/physiology , Rats
14.
Emerg Infect Dis ; 30(8): 1726-1729, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39043392

ABSTRACT

A woman in South Korea who underwent a colonoscopy for occasional gastrointestinal discomfort had 4 adult flukes of Echinostoma cinetorchis showing 37 collar spines around the oral sucker recovered from the terminal ileum through the ascending colon. Partial gene sequencing showed high identity with E. cinetorchis.


Subject(s)
Echinostoma , Echinostomiasis , Animals , Echinostoma/genetics , Echinostoma/isolation & purification , Republic of Korea , Humans , Female , Echinostomiasis/diagnosis , Echinostomiasis/parasitology , Echinostomiasis/drug therapy , Middle Aged , Phylogeny
15.
J Control Release ; 372: 885-900, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38971425

ABSTRACT

Statins are widely used to treat hyperlipidemia; however, their mechanism-inhibiting cholesterol production without promoting its utilization-causes problems, such as inducing diabetes. In our research, we develop, for the first time, a chemically engineered statin conjugate that not only inhibits cholesterol production but also enhances its consumption through its multifunctional properties. The novel rosuvastatin (RO) and ursodeoxycholic acid (UDCA) conjugate (ROUA) is designed to bind to and inhibit the core of the apical sodium-dependent bile acid transporter (ASBT), effectively blocking ASBT's function in the small intestine, maintaining the effect of rosuvastatin. Consequently, ROUA not only preserves the cholesterol-lowering function of statins but also prevents the reabsorption of bile acids, thereby increasing cholesterol consumption. Additionally, ROUA's ability to self-assemble into nanoparticles in saline-attributable to its multiple hydroxyl groups and hydrophobic nature-suggests its potential for a prolonged presence in the body. The oral administration of ROUA nanoparticles in animal models using a high-fat or high-fat/high-fructose diet shows remarkable therapeutic efficacy in fatty liver, with low systemic toxicity. This innovative self-assembling multifunctional molecule design approach, which boosts a variety of therapeutic effects while minimizing toxicity, offers a significant contribution to the advancement of drug development.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Nanoparticles , Organic Anion Transporters, Sodium-Dependent , Rosuvastatin Calcium , Symporters , Animals , Nanoparticles/chemistry , Organic Anion Transporters, Sodium-Dependent/antagonists & inhibitors , Organic Anion Transporters, Sodium-Dependent/metabolism , Symporters/antagonists & inhibitors , Symporters/metabolism , Male , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemistry , Rosuvastatin Calcium/administration & dosage , Humans , Mice, Inbred C57BL , Bile Acids and Salts/metabolism , Bile Acids and Salts/chemistry , Cholesterol/chemistry , Rats, Sprague-Dawley , Mice
16.
Fitoterapia ; 177: 106135, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39047845

ABSTRACT

A naturally occurring stilbene, resveratrol, shows promising effects in the treatment of malignant pleural mesothelioma (MPM) both as a single agent and in combination with chemotherapeutic drugs. To discover new anticancer agents targeting MPM, stilbene-targeted isolation was performed on the roots of Polygonum multiflorum Thunb., an herbal medicine rich in stilbene compounds. In this study, seven stilbene glycosides (1-7) were isolated, along with four non-stilbenes (8-11), of which compounds 4 and 9-11 have not previously been isolated from this species. Stiquinoside A (1) is a previously undescribed stilbene glycoside, and its structure was elucidated as (E)-2,3,5,4'-tetrahydroxystilbene 2-O-ß-d-quinovopyranoside based on 1D and 2D-NMR, HR-ESI-MS, and acid hydrolysis experiments. Compounds 1, 4, 6, and 8 significantly inhibit the growth of MPM cancer cells H2452. These results demonstrate the potential utility of stilbenes in new strategies for the treatment of MPM.


Subject(s)
Antineoplastic Agents, Phytogenic , Fallopia multiflora , Mesothelioma, Malignant , Plant Roots , Stilbenes , Humans , Stilbenes/pharmacology , Stilbenes/isolation & purification , Plant Roots/chemistry , Molecular Structure , Cell Line, Tumor , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Mesothelioma, Malignant/drug therapy , Fallopia multiflora/chemistry , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Glycosides/pharmacology , Glycosides/isolation & purification , Mesothelioma/drug therapy , Lung Neoplasms/drug therapy , China
17.
Nature ; 632(8024): 390-400, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39048830

ABSTRACT

Most cases of herpes simplex virus 1 (HSV-1) encephalitis (HSE) remain unexplained1,2. Here, we report on two unrelated people who had HSE as children and are homozygous for rare deleterious variants of TMEFF1, which encodes a cell membrane protein that is preferentially expressed by brain cortical neurons. TMEFF1 interacts with the cell-surface HSV-1 receptor NECTIN-1, impairing HSV-1 glycoprotein D- and NECTIN-1-mediated fusion of the virus and the cell membrane, blocking viral entry. Genetic TMEFF1 deficiency allows HSV-1 to rapidly enter cortical neurons that are either patient specific or derived from CRISPR-Cas9-engineered human pluripotent stem cells, thereby enhancing HSV-1 translocation to the nucleus and subsequent replication. This cellular phenotype can be rescued by pretreatment with type I interferon (IFN) or the expression of exogenous wild-type TMEFF1. Moreover, ectopic expression of full-length TMEFF1 or its amino-terminal extracellular domain, but not its carboxy-terminal intracellular domain, impairs HSV-1 entry into NECTIN-1-expressing cells other than neurons, increasing their resistance to HSV-1 infection. Human TMEFF1 is therefore a host restriction factor for HSV-1 entry into cortical neurons. Its constitutively high abundance in cortical neurons protects these cells from HSV-1 infection, whereas inherited TMEFF1 deficiency renders them susceptible to this virus and can therefore underlie HSE.


Subject(s)
Brain , Encephalitis, Herpes Simplex , Herpesvirus 1, Human , Membrane Proteins , Virus Internalization , Animals , Female , Humans , Male , Brain/cytology , Brain/metabolism , Brain/virology , Encephalitis, Herpes Simplex/virology , Encephalitis, Herpes Simplex/metabolism , Herpesvirus 1, Human/pathogenicity , Herpesvirus 1, Human/physiology , Homozygote , Interferon Type I/metabolism , Interferon Type I/immunology , Membrane Proteins/deficiency , Membrane Proteins/genetics , Membrane Proteins/metabolism , Nectins/genetics , Nectins/metabolism , Neurons/cytology , Neurons/metabolism , Neurons/virology , Pluripotent Stem Cells/cytology , Virus Replication , Child, Preschool , Young Adult , Pedigree
18.
Viruses ; 16(7)2024 Jun 21.
Article in English | MEDLINE | ID: mdl-39066165

ABSTRACT

Foot-and-mouth disease virus (FMDV) is a highly contagious virus that affects cloven-hoofed animals and causes severe economic losses in the livestock industry. Given that this high-risk pathogen has to be handled in a biosafety level (BSL)-3 facility for safety reasons and the limited availability of BSL-3 laboratories, experiments on FMDV call for more attention. Therefore, we aimed to develop an FMDV experimental model that can be handled in BSL-2 laboratories. The NanoBiT luciferase (Nano-luc) assay is a well-known assay for studying protein-protein interactions. To apply the NanoBiT split luciferase assay to the diagnosis and evaluation of FMD, we developed an inactivated HiBiT-tagged Asia1 Shamir FMDV (AS-HiBiT), a recombinant Asia1 shamir FMDV with HiBiT attached to the VP1 region of Asia1 shamir FMDV. In addition, we established LgBiT-expressing LF-BK cell lines, termed LgBit-LF-BK cells. It was confirmed that inactivated AS-HiBiT infected LgBiT-LF-BK cells and produced a luminescence signal by binding to the intracellular LgBiT of LgBiT-LF-BK cells. In addition, the luminescence signal became stronger as the number of LgBiT-LF-BK cells increased or the concentration of inactivated AS-HiBiT increased. Moreover, we confirmed that inactivated AS-HiBiT can detect seroconversion in sera positive for FMDV-neutralizing antibodies. This NanoBiT split luciferase assay system can be used for the diagnosis and evaluation of FMD and expanded to FMD-like virus models to facilitate the evaluation of FMDV vaccines and antibodies.


Subject(s)
Foot-and-Mouth Disease Virus , Foot-and-Mouth Disease , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Cell Line , Foot-and-Mouth Disease/diagnosis , Foot-and-Mouth Disease/virology , Foot-and-Mouth Disease Virus/genetics , Luciferases/genetics , Luciferases/metabolism
19.
Development ; 151(20)2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39023164

ABSTRACT

Stable transgenesis is a transformative tool in model organism biology. Although the sea urchin is one of the oldest animal models in cell and developmental biology, studies in this animal have largely relied on transient manipulation of wild animals, without a strategy for stable transgenesis. Here, we build on recent progress to develop a more genetically tractable sea urchin species, Lytechinus pictus, and establish a robust transgene integration method. Three commonly used transposons (Minos, Tol2 and piggyBac) were tested for non-autonomous transposition, using plasmids containing a polyubiquitin promoter upstream of a H2B-mCerulean nuclear marker. Minos was the only transposable element that resulted in significant expression beyond metamorphosis. F0 animals were raised to sexual maturity, and spawned to determine germline integration and transgene inheritance frequency, and to characterize expression patterns of the transgene in F1 progeny. The results demonstrate transgene transmission through the germline, the first example of a germline transgenic sea urchin and, indeed, of any echinoderm. This milestone paves the way for the generation of diverse transgenic resources that will dramatically enhance the utility, reproducibility and efficiency of sea urchin research.


Subject(s)
Animals, Genetically Modified , DNA Transposable Elements , Gene Transfer Techniques , Germ Cells , Lytechinus , Transgenes , Animals , DNA Transposable Elements/genetics , Germ Cells/metabolism , Lytechinus/genetics , Female , Male , Sea Urchins/genetics , Mitochondria Associated Membranes
20.
Ann Coloproctol ; 40(3): 210-216, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38946091

ABSTRACT

PURPOSE: As introduced, multimodal pain management bundle for ileostomy reversal may be considered to reduce postoperative pain and hospital stay. The aim of this study was to evaluate clinical efficacy of perioperative multimodal pain bundle for ileostomy. METHODS: Medical records of patients who underwent ileostomy reversal after rectal cancer surgery from April 2017 to March 2020 were analyzed. Sixty-seven patients received multimodal pain bundle protocol with ileostomy reversal (group A) and 41 patients underwent closure of ileostomy with conventional pain management (group B). RESULTS: Baseline characteristics, including age, sex, body mass index, American Society of Anesthesiologists classification, diabetes mellitus, and smoking history, were not significantly different between the groups. The pain score on postoperative day 1 was significant lower in group A (visual analog scale, 2.6 ± 1.3 vs. 3.2 ± 1.2; P = 0.013). Overall consumption of opioid in group A was significant less than group B (9.7 ± 9.5 vs. 21.2 ± 8.8, P < 0.001). Hospital stay was significantly shorter in group A (2.3 ± 1.5 days vs. 4.1 ± 1.5 days, P < 0.001). There were no significant differences between the groups in postoperative complication rate. CONCLUSION: Multimodal pain protocol for ileostomy reversal could reduce postoperative pain, usage of opioid and hospital stay compared to conventional pain management.

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