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1.
Microb Pathog ; 195: 106875, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39173849

RESUMEN

This study evaluated the probiotic properties, safety profile, and antioxidative and immune system-enhancing effects of Enterococcus faecium strains isolated from human infant feces. E. faecium KU22001, E. faecium KU22002, and E. faecium KU22005 exhibited potential probiotic properties; however, to eliminate concerns about toxin production and antibiotic resistance, the E. faecium strains were heat-treated prior to experimental usage. E. faecium KU22001 showed the highest antioxidant activity and lowest reactive oxygen species production among the three strains. The immune system-enhancing effects of heat-killed E. faecium strains were evaluated using a nitric oxide assay. E. faecium KU22001 induced an increase in the mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, and proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß, and interleukin-6 in RAW 264.7 cells. Furthermore, E. faecium KU22001 activated the mitogen-activated protein kinase pathway, which was a key regulator of the immune system. These results demonstrate the potential use of E. faecium KU22001 as a multifunctional food material.


Asunto(s)
Antioxidantes , Citocinas , Enterococcus faecium , Heces , Probióticos , Probióticos/farmacología , Ratones , Animales , Células RAW 264.7 , Humanos , Antioxidantes/metabolismo , Citocinas/metabolismo , Heces/microbiología , Óxido Nítrico/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/genética , Calor , Interleucina-6/metabolismo , Interleucina-6/genética , Factores Inmunológicos/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Interleucina-1beta/metabolismo , Interleucina-1beta/genética
2.
BMC Ophthalmol ; 24(1): 359, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39169293

RESUMEN

PURPOSE: To investigate the incidence of and risk factors for failure of detection of active fellow-eye neovascularization on optical coherence tomography(OCT) crosshair scans in patients with unilateral neovascular age-related macular degeneration(AMD). METHODS: In this retrospective study, patients who experienced the development of active neovascularization in the fellow eye during the follow-up period were included(n = 75). Cases in which the neovascularization in the fellow eye could be identified solely through crosshair scans were defined as the crosshair scan detection group(n = 63). Cases in which the aforementioned findings could not be identified through crosshair scans but could be identified through raster scans were defined as the raster scan detection group(n = 12). The factors were compared between the two groups. Risk factors related to undetected neovascularization on crosshair scans were additionally identified. RESULTS: Active fellow-eye neovascularization, was not detected on OCT crosshair scans in 12 cases(16.0%) but was identified on raster scans in all cases. There was a significant difference in the proportion of neovascularization types between the crosshair scan detection group and the raster scan detection group(P = 0.023). Among the 35 fellow-eye neovascularization cases in patients with type 3 macular neovascularization(MNV), 10(28.6%) were not detected on crosshair scans. Multivariate analysis revealed a significantly higher risk for undetectable fellow-eye neovascularization on crosshair scans in patients with type 3 MNV than in those with typical neovascular AMD(P = 0.037,ß = 9.600). CONCLUSIONS: Our findings suggest the need for routine OCT raster scans during fellow-eye examinations in patients with unilateral neovascular AMD, particularly when the first-affected eye is diagnosed with type 3 MNV.


Asunto(s)
Tomografía de Coherencia Óptica , Degeneración Macular Húmeda , Humanos , Tomografía de Coherencia Óptica/métodos , Estudios Retrospectivos , Masculino , Femenino , Anciano , Degeneración Macular Húmeda/diagnóstico , Anciano de 80 o más Años , Agudeza Visual , Neovascularización Coroidal/diagnóstico , Neovascularización Coroidal/diagnóstico por imagen , Diagnóstico Precoz , Angiografía con Fluoresceína/métodos , Factores de Riesgo , Estudios de Seguimiento , Persona de Mediana Edad
3.
Psychiatry Investig ; 21(7): 718-725, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39089697

RESUMEN

OBJECTIVE: Tacrolimus intrapatient variability (Tac IPV) has been considered a marker for post-graft risk. We investigated pre-transplant psychometric testing to predict Tac IPV after living kidney transplantation. METHODS: Minnesota Multiphasic Personality Inventory-2 (MMPI-2) examined during pre-transplant evaluation by 102 recipients were analyzed. Subjects were divided into two groups, low IPV (L-IPV) and high IPV (H-IPV), by cutoffs of Tac IPV: median of 24 and value of 30. T-scores of MMPI-2 scales were used to analyze difference between L-IPV and H-IPV using independent t-tests. Stepwise multiple logistic regression was used to test whether MMPI-2 scales affected Tac IPV. Confusion matrix of logistic regression was used to explain statistical power. Cutoff values of significant scales for H-IPV were analyzed by constructing receiver operating characteristic curves. RESULTS: Hysteria (Hy) and depression (D) scale scores and Tac IPV were associated in IPV 24 (odds ratio [OR]: 1.08, p<0.01 for Hy; OR: 0.93, p<0.01 for D) and IPV 30 models (OR: 1.09, p<0.01 for Hy; OR: 0.92, p<0.01 for D). Paranoia (Pa) scale scores were associated with Tac IPV in IPV 24 model (OR=1.10, p<0.01) and were significantly higher in H-IPV 24 (p<0.01). F1 scores of confusion matrix in IPV 24 and 30 models were 0.70 and 0.71, respectively. Cutoffs of Hy, D, and Pa scales were 51, 57, and 47, respectively. CONCLUSION: MMPI-2 profile is suggested as a predictor for high Tac IPV after living kidney transplantation.

4.
Ann Surg Treat Res ; 107(1): 42-49, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38978687

RESUMEN

Purpose: Intracorporeal anastomosis (IA) in laparoscopic right hemicolectomy has been associated with faster recovery in bowel function compared to extracorporeal anastomosis (EA). However, the technical difficulty of laparoscopic suturing technique and intraabdominal fecal contamination hinder many surgeons from implementing such a procedure. We introduce and compare a bridging technique designated as "semi-extracorporeal" anastomosis (SEA), which embraces the advantages and amends the drawbacks of IA and EA. Methods: Between May 2016 and October 2022, 100 patients who underwent laparoscopic right hemicolectomy were analyzed. All patients who received laparoscopic right hemicolectomy underwent one of the 3 anastomosis methods (EA, SEA, and IA) by a single colorectal surgeon at a single tertiary care hospital. Data including perioperative parameters and postoperative outcomes were analyzed by each group. Results: A total of 100 patients were reviewed. Thirty patients underwent EA; 50 and 20 patients underwent SEA and IA, respectively. Operation time (minute) was 170 (range, 100-285), 170 (range, 110-280), and 147.5 (range, 80-235) in EA, SEA, and IA, respectively (P = 0.010). Wound size was smaller in SEA and IA compared to EA (P < 0.001). IA was associated with a shorter time (day) to first flatus compared to SEA and EA (4 [range, 2-13] vs. 4 [range, 2-7] vs. 2.5 [range, 1-4], P < 0.001). Postoperative complication showed no statistical significance between the 3 groups. Conclusion: Semi-extracorporeal was an attractive bridging option for colorectal surgeons worrisome of the technical difficulty of IA while maintaining faster bowel recovery and smaller wound incisions compared to EA.

5.
Sci Adv ; 10(21): eadk3321, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38781340

RESUMEN

Symmetry plays a key role in determining the physical properties of materials. By Neumann's principle, the properties of a material remain invariant under the symmetry operations of the space group to which the material belongs. Continuous phase transitions are associated with a spontaneous reduction in symmetry. Less common are examples where proximity to a continuous phase transition leads to an increase in symmetry. We find signatures of an emergent tetragonal symmetry close to a charge density wave (CDW) bicritical point in a fundamentally orthorhombic material, ErTe3, for which the two distinct CDW phase transitions are tuned via anisotropic strain. We first establish that tension along the a axis favors an abrupt rotation of the CDW wave vector from the c to a axis and infer the presence of a bicritical point where the two continuous phase transitions meet. We then observe a divergence of the nematic elastoresistivity approaching this putative bicritical point, indicating an emergent tetragonality in the critical behavior.

6.
PLoS One ; 19(5): e0303871, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38768233

RESUMEN

This study aimed to investigate the impact of the cumulative burden of metabolic syndrome (MetS) on the incidence of retinal vein occlusion (RVO) in young adults. We included 1,408,093 subjects aged ≥20 and <40 years without a history of RVO who underwent four consecutive annual health examinations during 2009-2012 from the database of the Korean National Health Insurance Service. The metabolic burden was evaluated based on the cumulative number of MetS diagnoses at each health examination (0-4 times) and the cumulative number of each MetS component diagnosed at each health examination (0-4 times per MetS component). Cox proportional hazards models were used to estimate the risk of RVO according to metabolic burden. The risk of RVO was positively correlated with the cumulative number of MetS diagnoses over the four health examinations. All five MetS components were independently associated with an increased risk of RVO. Subgroup analysis for the impact of MetS on RVO occurrence revealed that MetS had a greater impact on female subjects (P <0.001). Prompt detection of metabolic derangements and their treatment might be important to decrease the risk of RVO in young adults, especially women.


Asunto(s)
Síndrome Metabólico , Oclusión de la Vena Retiniana , Humanos , Síndrome Metabólico/epidemiología , Síndrome Metabólico/complicaciones , Oclusión de la Vena Retiniana/epidemiología , Oclusión de la Vena Retiniana/etiología , Femenino , Masculino , Adulto , República de Corea/epidemiología , Factores de Riesgo , Adulto Joven , Modelos de Riesgos Proporcionales , Incidencia
7.
Front Psychiatry ; 15: 1336656, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38699452

RESUMEN

Background: Hwabyung is a Korean culture-bound syndrome characterized by anger-related physical and psychological symptoms. Depressive disorder is a common mental illness occurring worldwide, and has been reported to have a high comorbidity rate with Hwabyung. For patients with depressive disorders, differential diagnosis and combined treatment for Hwabyung should be considered. Mindfulness and Qigong may be effective alternatives for regulating emotions such as depression, anxiety, and anger. This study aims to investigate whether Mindfulness and Qigong Training for Self-Healing (MQT-SH) would improve emotional problems in patients with Hwabyung and depressive disorder. Methods: This study will be a two-arm block randomized controlled trial. A total of 64 participants will be recruited and randomly assigned to either experimental or control group. While the experimental group will perform MQT-SH for the first six weeks, the control group will receive no treatment. During the next six weeks, the control group will perform MQT-SH for ethical equity. Assessments will be conducted at baseline, post-intervention (6 weeks) and follow-up (12 weeks). The primary outcomes would be Hwabyung and depression, while the secondary outcomes would include anxiety, anger, and vitality. Discussion: This study will provide a basis for assessing the effectiveness of mindfulness and Qigong training in patients with Hwabyung and depressive disorder. Ethics and dissemination: This study was approved by the Institutional Review Board of Kyung-Hee University Oriental Medicine Hospital in Gangdong (KHNMCOH 2023-09-003). The results will be disseminated through peer-reviewed publications. Trial registration: This trial was registered with the Clinical Research Information Service (CRIS), Republic of Korea, No. KCT0008937 and was registered on November 10, 2023.

8.
Virus Res ; 342: 199325, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38309472

RESUMEN

The COVID-19 pandemic caused by SARS-CoV-2 becomes a serious threat to global health and requires the development of effective antiviral therapies. Current therapies that target viral proteins have limited efficacy with side effects. In this study, we investigated the antiviral activity of MIT-001, a small molecule reactive oxygen species (ROS) scavenger targeting mitochondria, against SARS-CoV-2 and other zoonotic viruses in vitro. The antiviral activity of MIT-001 was quantified by RT-qPCR and plaque assay. We also evaluated the functional analysis of MIT-001 by JC-1 staining to measure mitochondrial depolarization, total RNA sequencing to investigate gene expression changes, and immunoblot to quantify protein expression levels. The results showed that MIT-001 effectively inhibited the replication of B.1.617.2 and BA.1 strains, Zika virus, Seoul virus, and Vaccinia virus. Treatment with MIT-001 restored the expression of heme oxygenase-1 (HMOX1) and NAD(P)H: quinone oxidoreductase 1 (NqO1) genes, anti-oxidant enzymes reduced by SARS-CoV-2, to normal levels. The presence of MIT-001 also alleviated mitochondrial depolarization caused by SARS-CoV-2 infection. These findings highlight the potential of MIT-001 as a broad-spectrum antiviral compound that targets for zoonotic RNA and DNA viruses, providing a promising therapeutic approach to combat viral infection.


Asunto(s)
COVID-19 , Infección por el Virus Zika , Virus Zika , Humanos , Animales , SARS-CoV-2 , Especies Reactivas de Oxígeno , Pandemias , Peces , Antivirales/farmacología
9.
Front Psychiatry ; 15: 1302245, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38410677

RESUMEN

Background: The development of clinical practice guidelines in traditional medicine requires evidence that sufficiently reflects the medical field. Cardiac neurosis is a disease that occurs because of problems in the autonomic nervous system and is characterized by symptoms of the circulatory system that are representative of autonomic dysfunction. In traditional medicine, the heart is considered to be involved in mental health problems, and cardiac neurosis is accompanied by a variety of mental symptoms. Furthermore, there is a categorized diagnosis for cardiac neurosis, and active empirical research is being conducted in China. Objective: This study aimed to systematically review and quantitatively synthesize the effects of Korean medicine treatments in patients with cardiac neurosis to develop evidence-based clinical practice guidelines for the treatment of autonomic dysfunction. Methods: Nine databases were searched for articles published before September 13, 2022. The methodological quality of the studies was assessed using the RoB tool. The primary outcomes were somatization, depression, anxiety, and effectiveness rate. The secondary outcome was the rate of adverse effects. Results: Based on a systematic literature review, 151 randomized controlled trials were selected and analyzed. For patients with cardiac neurosis, herbal medicine, combined treatment of herbal medicine and Western medicine, combined treatment of herbal medicine and acupuncture, acupuncture, and combined treatment of acupuncture and Western medicine showed better overall effects than Western medicine alone. Furthermore, the combined treatment of herbal medicine and psychotherapy and that of herbal medicine, psychotherapy, and Western medicine showed an overall better effect than the combined treatment of Western medicine and psychotherapy. Conclusion: A meta-analysis of articles revealed the effectiveness of Korean medicine treatments and verified the effectiveness of a Korean medicine treatment alone, Korean medicine combined treatment, and combined treatment of Korean medicine and Western medicine on cardiac neurosis. Limitations included the inability to verify the cause of high heterogeneity between studies and the poor quality of the included studies. Nevertheless, this systematic review and meta-analysis of cardiac neurosis showed that the disease concept of traditional medicine can also be organized based on the latest research. Future research related to traditional diseases such as these should be conducted. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022347992, identifier CRD42022347992.

10.
Asian J Surg ; 47(1): 296-302, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37648541

RESUMEN

BACKGROUND: With a 5-year overall survival of less than 5%, colorectal peritoneal metastasis (CPM) patients are often managed with palliative chemotherapy (CTx). In the past few decades, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been introduced as a possible curative treatment for highly selective CPM patients. We share our experience of CRS and HIPEC given the unique characteristics of the medical system and the benefit of CRS and HIPEC in palliative setting. METHODS: From April 2017 to October 2021, CPM patients who underwent CRS and HIPEC were analyzed. Patients were allocated into perioperative and palliative CTx arm based on the duration between initial diagnosis of CPM to undergoing CRS and HIPEC of 6 months. Data including perioperative parameters, postoperative outcomes, and survival were analyzed with a median follow-up of 28.5 months. RESULTS: Twenty-six CPM patients underwent CRS and HIPEC. Mean time from diagnosis of CPM to CRS and HIPEC was 5.5 months with 14 patients in the perioperative arm and 12 patients in the palliative arm. Perioperative group showed a longer RFS of 13.5 months compared to 8 months in the palliative group. Median overall survival of palliative group was 41.50 months, and 18 patients among all groups are alive at the time of this report. CONCLUSION: CRS and HIPEC could be a treatment option for a carefully selected CPM patients performed by experienced surgeons. Overall survival of 41.50 months in palliative group compared to 16.8 months from conventional systemic CTx supports CRS and HIPEC even in palliative patients.


Asunto(s)
Neoplasias Colorrectales , Hipertermia Inducida , Neoplasias Peritoneales , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Terapia Combinada , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/secundario , Procedimientos Quirúrgicos de Citorreducción , Neoplasias Colorrectales/patología , Quimioterapia del Cáncer por Perfusión Regional , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tasa de Supervivencia , Estudios Retrospectivos
11.
Retina ; 44(4): 723-730, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37973042

RESUMEN

PURPOSE: To evaluate the predictive characteristics of fellow-eye geographic atrophy (GA) without neovascularization in patients with unilateral Type 3 macular neovascularization. METHODS: This retrospective study included 84 patients who were diagnosed with unilateral Type 3 macular neovascularization. Patients who developed fellow-eye neovascularization and those exhibiting GA without neovascularization at the final follow-up were included in the neovascularization and GA groups, respectively. The patient demographics and baseline fellow-eye characteristics were compared between the two groups. RESULTS: The mean follow-up period was 40.5 ± 11.5 months after diagnosis. Patients included in the GA group (n = 28) were significantly older (mean 77.4 ± 5.2 years vs. 74.2 ± 5.8 years, P = 0.016), had significantly thinner subfoveal choroidal thickness (mean 109.4 ± 36.8 µ m vs. 173.1 ± 77.6 µ m, P < 0.001), and had a significantly higher incidence of baseline GA (39.3% vs. 16.1%, P = 0.019) than those included in the neovascularization group (n = 56). In the multivariate analysis, subfoveal choroidal thickness showed a close negative association with the risk of GA rather than neovascularization ( P = 0.004, ß = 0.982, 95% confidence interval = 0.970-0.994). CONCLUSION: In patients with unilateral Type 3 macular neovascularization, older age, the presence of GA, and a thin choroid in the fellow eye were found to be indicative of a higher probability of progression toward fellow-eye GA instead of neovascularization may be potential candidates for future complement inhibitor treatments targeting fellow-eye GA.


Asunto(s)
Neovascularización Coroidal , Atrofia Geográfica , Degeneración Macular , Humanos , Atrofia Geográfica/diagnóstico , Estudios Retrospectivos , Neovascularización Coroidal/diagnóstico , Angiografía con Fluoresceína , Degeneración Macular/diagnóstico , Estudios de Seguimiento
12.
Nano Lett ; 23(24): 11409-11415, 2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38095312

RESUMEN

A prominent characteristic of 2D magnetic systems is the enhanced spin fluctuations, which reduce the ordering temperature. We report that a magnetic field of only 1000th of the Heisenberg superexchange interaction can induce a crossover, which for practical purposes is the effective ordering transition, at temperatures about 6 times the Néel transition in a site-diluted two-dimensional anisotropic quantum antiferromagnet. Such a strong magnetic response is enabled because the system directly enters the antiferromagnetically ordered state from the isotropic disordered state, skipping the intermediate anisotropic stage. The underlying mechanism is achieved on a pseudospin-half square lattice realized in the [(SrIrO3)1/(SrTiO3)2] superlattice thin film that is designed to linearly couple the staggered magnetization to external magnetic fields by virtue of the rotational symmetry-preserving Dzyaloshinskii-Moriya interaction. Our model analysis shows that the skipping of the anisotropic regime despite finite anisotropy is due to the enhanced isotropic fluctuations under moderate dilution.

13.
Quant Imaging Med Surg ; 13(11): 7459-7466, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37969625

RESUMEN

Background: Coronary bifurcation angles influence plaque initiation in the coronary artery, and changes in blood flow caused by tortuosity in the coronary arteries can reduce blood pressure distal to the tortuous portion of the coronary artery, leading to myocardial ischemia. We aimed to describe two factors (coronary artery tortuosity and bifurcation angle) as one descriptor for the evaluation of proximal left anterior descending coronary artery (LAD) disease. Methods: We reviewed the medical records of 133 consecutive patients who underwent computed tomography angiography (CTA) for angina symptoms between November 2019 and January 2020. The patients were divided into two groups according to the presence of significant LAD stenosis on CTA (defined as LAD stenosis >50%). The straight length of the vessel was measured using the central luminal line of the flow path, and, calculated using proprietary algorithms in TeraRecon software. We used three-dimensional volume rendering and two-dimensional axial images to measure the left main coronary artery (LM)-LAD angles. Results: In the univariate analysis, there were significant differences in the linear distance between the endpoints of the 20 mm actual curve of the LAD (d20), cosine value for LM-LAD angle (cosθ) <0.8, age, presence of hypertension or diabetes, and number of pack years [hazard ratio (HR): 2.70, 8.04, 1.05, 3.70, 2.82, and 1.04; P=0.029, P<0.001, P=0.020, P=0.024, P=0.021, and P=0.002, respectively]. However, in the multivariate analysis, the cosθ multiplied by d20 (d20*cosθ) <15.5, presence of hypertension and number of pack years (HR: 11.36, 4.54, and 1.04; P<0.001, P=0.019, and P=0.003, respectively) were predictors of significant proximal LAD stenosis. Conclusions: As the tortuosity and LM-LAD angle increased (d20 and cosθ decreased, respectively), the chance of proximal LAD lesions formation increased. d20*cosθ might be useful as a predictor of proximal LAD stenosis.

14.
Sci Adv ; 9(47): eadj5200, 2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-38000034

RESUMEN

Field-induced superconductivity is a rare phenomenon where an applied magnetic field enhances or induces superconductivity. Here, we use applied stress as a control switch between a field-tunable superconducting state and a robust non-field-tunable state. This marks the first demonstration of a strain-tunable superconducting spin valve with infinite magnetoresistance. We combine tunable uniaxial stress and applied magnetic field on the ferromagnetic superconductor Eu(Fe0.88Co0.12)2As2 to shift the field-induced zero-resistance temperature between 4 K and a record-high value of 10 K. We use x-ray diffraction and spectroscopy measurements under stress and field to reveal that strain tuning of the nematic order and field tuning of the ferromagnetism act as independent control parameters of the superconductivity. Combining comprehensive measurements with DFT calculations, we propose that field-induced superconductivity arises from a novel mechanism, namely, the uniquely dominant effect of the Eu dipolar field when the exchange field splitting is nearly zero.

15.
Phys Rev Lett ; 131(18): 186701, 2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37977621

RESUMEN

The Fe intercalated transition metal dichalcogenide (TMD), Fe_{1/3}NbS_{2}, exhibits remarkable resistance switching properties and highly tunable spin ordering phases due to magnetic defects. We conduct synchrotron x-ray scattering measurements on both underintercalated (x=0.32) and overintercalated (x=0.35) samples. We discover a new charge order phase in the overintercalated sample, where the excess Fe atoms lead to a zigzag antiferromagnetic order. The agreement between the charge and magnetic ordering temperatures, as well as their intensity relationship, suggests a strong magnetoelastic coupling as the mechanism for the charge ordering. Our results reveal the first example of a charge order phase among the intercalated TMD family and demonstrate the ability to stabilize charge modulation by introducing electronic correlations, where the charge order is absent in bulk 2H-NbS_{2} compared to other pristine TMDs.

16.
Nat Commun ; 14(1): 5728, 2023 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-37714840

RESUMEN

Arachidonic and adrenic acids in the membrane play key roles in ferroptosis. Here, we reveal that lipoprotein-associated phospholipase A2 (Lp-PLA2) controls intracellular phospholipid metabolism and contributes to ferroptosis resistance. A metabolic drug screen reveals that darapladib, an inhibitor of Lp-PLA2, synergistically induces ferroptosis in the presence of GPX4 inhibitors. We show that darapladib is able to enhance ferroptosis under lipoprotein-deficient or serum-free conditions. Furthermore, we find that Lp-PLA2 is located in the membrane and cytoplasm and suppresses ferroptosis, suggesting a critical role for intracellular Lp-PLA2. Lipidomic analyses show that darapladib treatment or deletion of PLA2G7, which encodes Lp-PLA2, generally enriches phosphatidylethanolamine species and reduces lysophosphatidylethanolamine species. Moreover, combination treatment of darapladib with the GPX4 inhibitor PACMA31 efficiently inhibits tumour growth in a xenograft model. Our study suggests that inhibition of Lp-PLA2 is a potential therapeutic strategy to enhance ferroptosis in cancer treatment.


Asunto(s)
Ferroptosis , Neoplasias , Humanos , 1-Alquil-2-acetilglicerofosfocolina Esterasa/antagonistas & inhibidores , Metabolismo de los Lípidos/efectos de los fármacos , Neoplasias/tratamiento farmacológico
17.
Cell Death Dis ; 14(8): 567, 2023 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-37633973

RESUMEN

Ferroptosis, a type of cell death induced by lipid peroxidation, has emerged as a novel anti-cancer strategy. Cancer cells frequently acquire resistance to ferroptosis. However, the underlying mechanisms are poorly understood. To address this issue, we conducted a thorough investigation of the genomic and transcriptomic data derived from hundreds of human cancer cell lines and primary tissue samples, with a particular focus on non-small cell lung carcinoma (NSCLC). It was observed that mutations in Kelch-like ECH-associated protein 1 (KEAP1) and subsequent nuclear factor erythroid 2-related factor 2 (NRF2, also known as NFE2L2) activation are strongly associated with ferroptosis resistance in NSCLC. Additionally, AIFM2 gene, which encodes ferroptosis suppressor protein 1 (FSP1), was identified as the gene most significantly correlated with ferroptosis resistance, followed by multiple NRF2 targets. We found that inhibition of NRF2 alone was not sufficient to reduce FSP1 protein levels and promote ferroptosis, whereas FSP1 inhibition effectively sensitized KEAP1-mutant NSCLC cells to ferroptosis. Furthermore, we found that combined inhibition of FSP1 and NRF2 induced ferroptosis more intensely. Our findings imply that FSP1 is a crucial suppressor of ferroptosis whose expression is partially dependent on NRF2 and that synergistically targeting both FSP1 and NRF2 may be a promising strategy for overcoming ferroptosis resistance in cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Ferroptosis , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Ferroptosis/genética , Proteína 1 Asociada A ECH Tipo Kelch/genética , Neoplasias Pulmonares/genética , Factor 2 Relacionado con NF-E2/genética
18.
Korean J Intern Med ; 38(5): 641-650, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37635283

RESUMEN

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.


Asunto(s)
Artritis Gotosa , Gota , Humanos , Gota/diagnóstico , Gota/tratamiento farmacológico , Pueblo Asiatico , Consenso , República de Corea
19.
Exp Mol Med ; 55(8): 1620-1631, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37612411

RESUMEN

Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. This process contributes to cellular and tissue damage in various human diseases, such as cardiovascular diseases, neurodegeneration, liver disease, and cancer. Although polyunsaturated fatty acids (PUFAs) in membrane phospholipids are preferentially oxidized, saturated/monounsaturated fatty acids (SFAs/MUFAs) also influence lipid peroxidation and ferroptosis. In this review, we first explain how cells differentially synthesize SFA/MUFAs and PUFAs and how they control fatty acid pools via fatty acid uptake and ß-oxidation, impacting ferroptosis. Furthermore, we discuss how fatty acids are stored in different lipids, such as diacyl or ether phospholipids with different head groups; triglycerides; and cholesterols. Moreover, we explain how these fatty acids are released from these molecules. In summary, we provide an integrated view of the diverse and dynamic metabolic processes in the context of ferroptosis by revisiting lipidomic studies. Thus, this review contributes to the development of therapeutic strategies for ferroptosis-related diseases.


Asunto(s)
Ferroptosis , Metabolismo de los Lípidos , Humanos , Lipidómica , Ácidos Grasos , Transporte Biológico
20.
J Ocul Pharmacol Ther ; 39(9): 653-660, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37504966

RESUMEN

Purpose: To compare the effectiveness of intravitreal injections of brolucizumab and aflibercept in patients with polypoidal choroidal vasculopathy (PCV). Methods: In total, 62 treatment-naive PCV eyes (62 patients) treated with intravitreal brolucizumab or aflibercept were analyzed retrospectively. All patients received a monthly loading injection of antivascular endothelial growth factor for 3 months, followed by further injections as required. Visual and anatomical outcomes were compared between drugs after 12 months of treatment. Results: The improvement in best-corrected visual acuity after 12 months of treatment was not significantly different between the brolucizumab-treated (22 eyes) and aflibercept-treated groups (40 eyes). However, in the brolucizumab-treated group, there was a significantly greater decrease in central retinal thickness (172 vs. 147 µm; P = 0.031) and subfoveal choroidal thickness after treatment (51 vs. 29 µm; P = 0.025). In addition, the regression rate of polypoidal lesions was significantly higher in the brolucizumab-treated group (77.3%, 17/22 eyes) than that in the aflibercept-treated group (45.0%, 18/40 eyes; P = 0.014). Sterile intraocular inflammation showing mild vitritis was observed in 1 of the 22 eyes (4.5%) of brolucizumab-treated patients. Conclusion: Intravitreal brolucizumab injections for PCV showed visual improvement comparable to that of aflibercept during the 12-month treatment period. However, brolucizumab was more effective than aflibercept for the regression of polypoidal lesions and caused a greater decrease in central retinal thickness and subfoveal choroidal thickness.


Asunto(s)
Inhibidores de la Angiogénesis , Neovascularización Coroidal , Humanos , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Vasculopatía Coroidea Polipoidea , Neovascularización Coroidal/diagnóstico , Neovascularización Coroidal/tratamiento farmacológico , Estudios Retrospectivos , Factor A de Crecimiento Endotelial Vascular , Tomografía de Coherencia Óptica , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/farmacología , Proteínas Recombinantes de Fusión/uso terapéutico , Inyecciones Intravítreas , Resultado del Tratamiento , Angiografía con Fluoresceína
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