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1.
Nat Immunol ; 22(9): 1127-1139, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34413521

RESUMEN

Follicular helper T (TFH) cells are a specialized subset of CD4+ T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of TFH cell survival remains unclear. Here we report that TFH cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for TFH cell survival. The deletion of GPX4 in T cells selectively abrogated TFH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFH cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium-GPX4-ferroptosis axis in regulating TFH homeostasis, which can be targeted to enhance TFH cell function in infection and following vaccination.


Asunto(s)
Ferroptosis/fisiología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Selenio/farmacología , Células T Auxiliares Foliculares/fisiología , Adolescente , Adulto , Animales , Supervivencia Celular/inmunología , Niño , Femenino , Centro Germinal/citología , Centro Germinal/inmunología , Homeostasis/efectos de los fármacos , Homeostasis/genética , Humanos , Inmunidad Humoral/inmunología , Vacunas contra la Influenza/inmunología , Peroxidación de Lípido/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias/fisiología , Ovalbúmina , Células T Auxiliares Foliculares/inmunología , Vacunación , Adulto Joven
3.
Allergy ; 79(5): 1230-1241, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38403941

RESUMEN

BACKGROUND: Identifying predictive biomarkers for allergen immunotherapy response is crucial for enhancing clinical efficacy. This study aims to identify such biomarkers in patients with allergic rhinitis (AR) undergoing subcutaneous immunotherapy (SCIT) for house dust mite allergy. METHODS: The Tongji (discovery) cohort comprised 72 AR patients who completed 1-year SCIT follow-up. Circulating T and B cell subsets were characterized using multiplexed flow cytometry before SCIT. Serum immunoglobulin levels and combined symptom and medication score (CSMS) were assessed before and after 12-month SCIT. Responders, exhibiting ≥30% CSMS improvement, were identified. The random forest algorithm and logistic regression analysis were used to select biomarkers and establish predictive models for SCIT efficacy in the Tongji cohort, which was validated in another Wisco cohort with 43 AR patients. RESULTS: Positive SCIT response correlated with higher baseline CSMS, allergen-specific IgE (sIgE)/total IgE (tIgE) ratio, and frequencies of Type 2 helper T cells, Type 2 follicular helper T (TFH2) cells, and CD23+ nonswitched memory B (BNSM) and switched memory B (BSM) cells, as well as lower follicular regulatory T (TFR) cell frequency and TFR/TFH2 cell ratio. The random forest algorithm identified sIgE/tIgE ratio, TFR/TFH2 cell ratio, and BNSM frequency as the key biomarkers discriminating responders from nonresponders in the Tongji cohort. Logistic regression analysis confirmed the predictive value of a combination model, including sIgE/tIgE ratio, TFR/TFH2 cell ratio, and CD23+ BSM frequency (AUC = 0.899 in Tongji; validated AUC = 0.893 in Wisco). CONCLUSIONS: A T- and B-cell signature combination efficiently identified SCIT responders before treatment, enabling personalized approaches for AR patients.


Asunto(s)
Biomarcadores , Desensibilización Inmunológica , Pyroglyphidae , Rinitis Alérgica , Humanos , Rinitis Alérgica/terapia , Rinitis Alérgica/inmunología , Masculino , Desensibilización Inmunológica/métodos , Animales , Femenino , Adulto , Pyroglyphidae/inmunología , Resultado del Tratamiento , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Persona de Mediana Edad , Adulto Joven , Alérgenos/inmunología , Alérgenos/administración & dosificación , Antígenos Dermatofagoides/inmunología , Inyecciones Subcutáneas , Adolescente , Pronóstico
4.
Chemistry ; 30(17): e202303553, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38251274

RESUMEN

Domino reaction of benzo[d]thiazole-2-methylamine (S1) has been developed in the presence of MnCl2 ⋅ 4H2O, leading to tetrasubstituted pyrrole coordinated dinuclear Mn(II) complex 1 ([MnClP]2, P-=2,3,4,5-tetrakis(benzo[d]thiazol-2-yl)pyrrol-1-ide). The reaction process has been studied by assigning a series of intermediates based on time-dependent mass spectrometry, control experiments, crystallography, and density functional theory (DFT) theoretical calculation. A plausible mechanism involving an unprecedented divergent-convergent domino sequence has been proposed. Compound S1 could be activated by MnCl2 ⋅ 4H2O via coordination, which divergently produces two intermediates imine II (1-(benzo[d]thiazol-2-yl)-N-(benzo[d]thiazol-2-ylmethyl)methanimine) and alkene C (1,2-bis(benzo[d]thiazol-2-yl)ethene) through oxidative self-condensation and free radical coupling followed by elimination, respectively. They could then react with each other convergently via formal [3+2] cycloaddition to give deprotonated tetrasubstituted pyrrole coordinated intermediate [MnClP] after aromatization. Dimerization of [MnClP] produces the final product 1. Three C-C bonds and one C-N bond are formed through this six-step domino sequence. The corresponding organic skeleton (HP: 2,2',2'',2'''-(1H-pyrrole-2,3,4,5-tetrayl)tetrakis(benzo[d]thiazole)) has been obtained from 1 and shows a higher fluorescent quantum yield (52 %) than the reported 3,4-diphenyl substituted analogue 2,2'-(3,4-diphenyl-1H-pyrrole-2,5-diyl)bis(benzo[d]thiazole) (DPB) (42 %).

5.
FASEB J ; 37(6): e22992, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37219513

RESUMEN

Oxidative stress and lipid metabolism disorder caused by estrogen deficiency are regarded as the main causes of postmenopausal atherosclerosis, but the underlying mechanisms remain still unclear. In this study, ovariectomized (OVX) female ApoE-/- mice fed with high-fat diet were used to imitate postmenopausal atherosclerosis. The atherosclerosis progression was significantly accelerated in OVX mice, accompanied by the upregulation of ferroptosis indicators, including increased lipid peroxidation and iron deposition in the plaque and the plasma. While both estradiol (E2) and ferroptosis inhibitor ferrostatin-1 alleviated atherosclerosis in OVX mice, with the inhibition of lipid peroxidation and iron deposition, as well as the upregulation of xCT and GPX4, especially in endothelial cells. We further investigated the effects of E2 on ferroptosis in endothelial cells induced by oxidized-low-density lipoprotein or ferroptosis inducer Erastin. It was found that E2 exhibited anti-ferroptosis effect through antioxidative functions, including improving mitochondrial dysfunction and upregulating GPX4 expression. Mechanistically, NRF2 inhibition attenuated the effect of E2 against ferroptosis as well as the upregulation of GPX4. Our findings revealed that endothelial cell ferroptosis played a pivotal role in postmenopausal atherosclerosis progression, and the NRF2/GPX4 pathway activation contributed to the protection of E2 against endothelial cell ferroptosis.


Asunto(s)
Aterosclerosis , Factor 2 Relacionado con NF-E2 , Animales , Femenino , Ratones , Células Endoteliales , Estrógenos/deficiencia , Hierro , Posmenopausia
6.
Cell Commun Signal ; 22(1): 41, 2024 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-38229167

RESUMEN

BACKGROUND: Tar is the main toxic of cigarettes, and its effect on atherosclerosis progression and the underlying mechanisms remain largely unknown. Vascular smooth muscle cells (VSMCs) play a key role in atherogenesis and plaque vulnerability. The present study sought to investigate the mechanism of atherosclerosis progression through tar-induced VSMC necroptosis, a recently described form of necrosis. METHODS: The effect of tar on atherosclerosis progression and VSMC necroptosis was examined in ApoE-/- mice and cultured VSMCs. The role of necroptosis in tar-induced plaque development was evaluated in RIPK3-deletion mice (ApoE-/-RIPK3-/-). The key proteins of necroptosis in carotid plaques of smokers and non-smokers were also examined. Quantitative proteomics of mice aortas was conducted to further investigate the underlying mechanism. Pharmacological approaches were then applied to modulate the expression of targets to verify the regulatory process of tar-induced necroptosis. RESULTS: Tar administration led to increased atherosclerotic plaque area and reduced collagen and VSMCs in ApoE-/- mice. The expression of RIPK1、RIPK3、and MLKL in VSMCs of plaques were all increased in tar-exposed mice and smokers. RIPK3 deletion protected against VSMC loss and plaque progression stimulated by tar. In mechanistic studies, quantitative proteomics analysis of ApoE-/- mice aortas suggested that tar triggered endoplasmic reticulum (ER) stress. PERK-eIF2α-CHOP axis was activated in tar-treated VSMCs and atherosclerotic plaque. Inhibition of ER stress using 4PBA significantly reduced plaque progression and VSMC necroptosis. Further study revealed that ER stress resulted in calcium (Ca2+) release into mitochondria and cytoplasm. Elevated Ca2+ levels lead to mitochondrial dysfunction and excessive reactive oxygen species (ROS) production, which consequently promote RIPK3-dependent necroptosis. In addition, Ca2+/calmodulin-dependent protein kinase II (CaMKII) activated by cytosolic Ca2+ overload binds to RIPK3, accounting for necroptosis. CONCLUSION: The findings revealed that cigarette tar promoted atherosclerosis progression by inducing RIPK3-dependent VSMC necroptosis and identified novel avenues of ER stress and Ca2+ overload.


Asunto(s)
Aterosclerosis , Placa Aterosclerótica , Breas , Ratones , Animales , Placa Aterosclerótica/metabolismo , Músculo Liso Vascular , Necroptosis , Aterosclerosis/metabolismo , Estrés del Retículo Endoplásmico , Apolipoproteínas E/metabolismo , Miocitos del Músculo Liso/metabolismo
7.
Inorg Chem ; 63(13): 6033-6041, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38500387

RESUMEN

We report the synthesis and structural characterization of a 2D metal-organic framework with AB-packing layers, [Co2(pybz)2(CH3COO)2]·DMF (Co2, pybz= 4-(4-pyridyl)benzoate), containing a stable (4,4)-grid network fabricated by paddle-wheel nodes, ditopic pybz, and acetate ligands. After removal of the guest, the layer structure is retained but reorganized into an ABCD packing mode in the activated phase (Co2a). Consequently, the intralayer square windows (7.2 × 5.0 Å2) close, while the interlayer separation is decreased slightly from 3.69 to 3.45 Å, leaving a narrow gap. Importantly, the dangling methyl group of the acetate with H-bonds to the adjacent layers and also the well-distributed π-π interactions between the aromatic rings of neighboring layers facilitate the structural stability. These weak supramolecular interactions further allow for favorable dynamic exfoliation of the layers, which promotes efficient adsorption of C2H2 (41.6 cm3 g-1) over CO2 with an adsorption ratio of 6.3 (0.5 bar, 298 K). The effective separation performance of equimolar C2H2/CO2 was verified by cycling breakthrough experiments and was even tolerable to moisture (R.H = 52%). DFT calculations, in situ PXRD, and PDF characterization reveal that the favorable retention of C2H2 rather than that of CO2 is due to its H-bond formation with the paddle-wheel oxygen atoms that triggers the increase in interlayer separation during C2H2 adsorption.

8.
Environ Res ; 247: 118113, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38199473

RESUMEN

The challenge of meeting discharge standards for tetrabromobisphenol A (TBBPA) production wastewater, characterized by high concentrations of organic by-products, necessitates effective treatment methods. This study identifies 2,4-dibromophenol, 2,6-dibromophenol, 2,4,6-tribromophenol, chlorobenzene, and toluene as the primary organic by-product pollutants. A coagulation-centered three-step approach was established for TBBPA industrial wastewater treatment. The initial step involves acidification treatment to exploit the reduced solubility of 2,4-dibromophenol, 2,6-dibromophenol, and 2,4,6-tribromophenol under acidic conditions, with the optimal pH determined as 2.7-3.1. An acid-activated montmorillonite coagulant (AMC), prepared through roasting and high-pressure acid leaching, exhibits a distinctive "Core-shell" structure, contributing significantly to the combined coagulation and adsorption mechanism. The acid-soluble aluminum salts in AMC form positively charged flocs, electrostatically attracting negatively charged organic compounds in the wastewater. Simultaneously, the porous insoluble silicon framework displays strong adsorption capacity for pollutants. The removal efficiencies for toluene, chlorobenzene, 2,4-dibromophenol, 2,6-dibromophenol, and 2,4,6-tribromophenol reached 88.2%, 89.1%, 88.8%, 87.1%, and 89.4%, respectively. Elemental analysis reveals that the coloration of the wastewater stems from complexation reactions between phenolic compounds and Fe3+, originating from the corrosion of iron or steel reaction vessel. Post-treatment with cation exchange resin resulted in removal efficiencies of 5.2%, 59.1%, 80.2%, 77.9%, and 88.3% for the five substances, respectively. This study outlines a crucial pathway for the effective purification of TBBPA wastewater.


Asunto(s)
Contaminantes Ambientales , Fenoles , Bifenilos Polibrominados , Contaminantes Químicos del Agua , Aguas Residuales , Contaminantes Ambientales/análisis , Contaminantes Químicos del Agua/análisis , Clorobencenos/análisis , Tolueno/análisis , Adsorción
9.
Artículo en Inglés | MEDLINE | ID: mdl-38401070

RESUMEN

Background: Diabetes, a chronic disease metabolic disorder, commonly affects people. It is well-documented that aerobic exercise significantly reduces blood glucose in diabetic conditions. This study aimed to demonstrate the role of aerobic exercise on T2DM patients and cognitive impairment. Methods: We selected studies that published random controlled trials (RCTs) on the effects of aerobic exercise on cognitive function in patients with T2DM. However, the animal trials were we excluded in this study. We retrieved the data of random controlled trials from 8 databases based on the influences of aerobic exercise on cognitive function in patients with type 2 diabetes mellitus (T2DM). We utilized RevMan 5.3 software to analyze the data after evaluating the literature. Results: We selected 685 studies based on the information in the abstract and title after deleting the duplicate references. Then, we investigated the full text of 15. After full-text evaluation,we selected 10 random controlled trials to perform this comprehensive meta-analysis. We found that 10 studies derived the information of cognitive function between the test and the control groups and the cognitive function is significantly higher in the experimental group (SMD: 1.88; 95% Cl: 0.91,2.84; P < .01) than the control group. Moreover, the experimental group showed significantly higher minimum mental state examination (MMSE) (SMD: 2.06; 95% Cl: 0.96,3.14; P < .01) and Montreal Cognitive Assessment (MoCA) (SMD:1.62; 95% Cl: 0.54, 2.69; P < .01) than the normal group. Conclusion: Our findings demonstrated that aerobic exercise is crucially potent in T2DM patients and cognitive impairment, as evidenced by total cognitive function, MMSE, and MoCA. The above results should be warranted to verify with sophisticated clinical trials. In the future, aerobic exercise is suggested to guide patients'srecovery.

10.
Ren Fail ; 46(2): 2365393, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38874139

RESUMEN

INTRODUCTION: The Agatston coronary artery calcification score (CACS) is an assessment index for coronary artery calcification (CAC). This study aims to explore the characteristics of CAC in end-stage kidney disease (ESKD) patients and establish a predictive model to assess the risk of severe CAC in patients. METHODS: CACS of ESKD patients was assessed using an electrocardiogram-gated coronary computed tomography (CT) scan with the Agatston scoring method. A predictive nomogram model was established based on stepwise regression. An independent validation cohort comprised of patients with ESKD from multicentres. RESULTS: 369 ESKD patients were enrolled in the training set, and 127 patients were included in the validation set. In the training set, the patients were divided into three subgroups: no calcification (CACS = 0, n = 98), mild calcification (0 < CACS ≤ 400, n = 141) and severe calcification (CACS > 400, n = 130). Among the four coronary branches, the left anterior descending branch (LAD) accounted for the highest proportion of calcification. Stepwise regression analysis showed that age, dialysis vintage, ß-receptor blocker, calcium-phosphorus product (Ca × P), and alkaline phosphatase (ALP) level were independent risk factors for severe CAC. A nomogram that predicts the risk of severe CAC in ESKD patients has been internally and externally validated, demonstrating high sensitivity and specificity. CONCLUSION: CAC is both prevalent and severe in ESKD patients. In the four branches of the coronary arteries, LAD calcification is the most common. Our validated nomogram model, based on clinical risk factors, can help predict the risk of severe coronary calcification in ESKD patients who cannot undergo coronary CT analysis.


Asunto(s)
Enfermedad de la Arteria Coronaria , Fallo Renal Crónico , Nomogramas , Calcificación Vascular , Humanos , Masculino , Femenino , Fallo Renal Crónico/complicaciones , Persona de Mediana Edad , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/complicaciones , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/complicaciones , Anciano , Factores de Riesgo , Índice de Severidad de la Enfermedad , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Tomografía Computarizada por Rayos X , Adulto , Medición de Riesgo
11.
J Formos Med Assoc ; 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38331636

RESUMEN

BACKGROUND: /Purpose: Leukocyte esterase strips have been widely used to detect the presence of leukocyte in human body fluids. We investigated the correlation between fecal leukocyte esterase (FLE) and fecal calprotectin (FC) levels and compared manual with machine automated interpretation of FLE level. METHODS: This prospective study enrolled inflammatory bowel disease and colitis patients in National Taiwan University Hospital from Dec 2021 to Feb 2022. FLE and FC measured using the same sample were compared with various FC cutoff values. The correlation between values indicated by the two tests was analyzed. Sensitivity, specificity, positive and negative predictive values, and area under the receiver operating characteristic curve (AUROC) were calculated using SAS. RESULTS: A total of 103 samples were analyzed. The correlation between FLE and FC level was moderate and positive (r = 0.3505, P = 0.0003). With an FLE reading more than 1+ indicating mucosa inflammation, when the FC cutoff was 50, 250, and 500 mg/kg, the sensitivities of FLE readings were 60.3 %, 74.3 %, and 84.6 %, respectively, and the specificities were 62.9 %, 58.8 %, and 58.4 %, respectively. With an FLE reading greater than 1+ indicating mucosa inflammation, FLE reflected FC with AUROC values at the optimal cutoff (500 mg/kg) of 0.72. No difference was noted between manual and machine readings for FLE. CONCLUSION: Positive FLE can predict FC levels of more than 500 mg/kg. The test is widely available, produces results on the same day, and is low cost; therefore, FLE should be further investigated for use in bowel inflammation monitoring.

12.
Nano Lett ; 23(9): 4066-4073, 2023 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-37097764

RESUMEN

Reticular chemistry provides opportunities to design solid-state electrolytes (SSEs) with modular tunability. However, SSEs based on modularly designed crystalline metal-organic frameworks (MOFs) often require liquid electrolytes for interfacial contact. Monolithic glassy MOFs can have liquid processability and uniform lithium conduction, which is promising for the reticular design of SSE without liquid electrolytes. Here, we develop a generalizable strategy for the modular design of noncrystalline SSEs based on a bottom-up synthesis of glassy MOFs. We demonstrate such a strategy by linking polyethylene glycol (PEG) struts and nanosized titanium-oxo clusters into network structures termed titanium alkoxide networks (TANs). The modular design allows the incorporation of PEG linkers with different molecular weights, which give optimal chain flexibility for high ionic conductivity, and the reticular coordinative network provides a controlled degree of cross-linking that gives adequate mechanical strength. This research shows the power of reticular design in noncrystalline molecular framework materials for SSEs.

13.
J Environ Manage ; 352: 120092, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38232596

RESUMEN

Heavy metals (HMs) have been widely reported to pose an adverse effect on anaerobic ammonia oxidation (anammox) bacteria, yet the underlying mechanisms remain unclear. This study provides new insights into the potential mechanisms of interaction between HMs and functional enzymes through big date analysis, molecular docking and molecular dynamics simulation. The statistical analysis indicated that 10 mg/L Cu(II) and Cd(II) reduced nitrogen removal rate (NRR) by 85% and 43%, while 5 mg/L Fe(II) enhanced NRR by 29%. Additionally, the results of molecular simulations provided a microscopic interpretation for these macroscopic data. Molecular docking revealed that Hg(II) formed a distinctive binding site on ferritin, while other HMs resided at iron oxidation sites. Furthermore, HMs exhibited distinct binding sites on hydrazine dehydrogenase. Concurrently, the molecular dynamics simulation results further substantiated their capacity to form complexes. Cu(II) displayed the strongest binding affinity with ferritin for -1576 ± 79 kJ/mol in binding free energy calculation. Moreover, Cd(II) bound to ferritin and HDH for -1052.67 ± 58.49 kJ/mol, -290.02 ± 49.68 kJ/mol, respectively. This research addressed a crucial knowledge gap, shedding light on potential applications for remediating heavy metal-laden industrial wastewater.


Asunto(s)
Cadmio , Metales Pesados , Simulación del Acoplamiento Molecular , Oxidación Anaeróbica del Amoníaco , Simulación de Dinámica Molecular , Macrodatos , Metales Pesados/química , Iones , Ferritinas , Oxidación-Reducción , Reactores Biológicos/microbiología , Nitrógeno , Aguas del Alcantarillado , Desnitrificación , Anaerobiosis
14.
Fish Physiol Biochem ; 50(1): 225-237, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37594622

RESUMEN

The aim of this study was to investigate the effect of dietary vitamin A on juvenile Chinese perch (Siniperca chuatsi). Chinese perch were fed with five experimental diets containing 0, 20, 40, 60, and 80 mg VA·kg-1 for 8 weeks. Results showed that dietary vitamin A significantly influenced the fish's growth, feed utilization, glucose and lipid metabolism, appetite, and antioxidant capacity. Vitamin A-supplemented groups had higher weight gain rate (WGR) and specific growth rate (SGR) compared to the control group. Feed conversion ratio (FCR) was also lower in the vitamin A-supplemented groups. Dietary vitamin A had no significant effect on the survival rate (SR). Compared to the control group, fish fed with vitamin A had increased feed intake (FI), and the expression of appetite-promoting genes (npy and agrp) was significantly higher in the 40 mg VA·kg-1 group. Vitamin A also enhanced the utilization of dietary protein by Chinese perch. The serum glucose content of the fish fed with 40 mg VA·kg-1 diet was significantly higher than that of the control group and 20 mg VA·kg-1 diet, indicating that the promoting effect of VA on gluconeogenesis was greater than that on glycolysis. Additionally, dietary vitamin A increased the expression of lipid metabolism-related genes (hl and fas) and antioxidant genes (nrf2 and gpx) in the fish. These results suggest that the optimal vitamin A requirement of juvenile Chinese perch bream was estimated to be 37.32 mg VA·kg-1 based on broken-line regression analysis of WGR. In conclusion, this study provides valuable insights into the potential benefits of dietary vitamin A on the growth, metabolism, and antioxidant capacity of Chinese perch.


Asunto(s)
Antioxidantes , Percas , Animales , Antioxidantes/metabolismo , Metabolismo de los Lípidos , Vitamina A/farmacología , Vitamina A/metabolismo , Apetito , Glucosa/metabolismo , Suplementos Dietéticos/análisis , Dieta/veterinaria , Alimentación Animal/análisis
15.
BMC Oral Health ; 24(1): 704, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890602

RESUMEN

BACKGROUND: Odontogenic carcinoma with dentinoid (OCD) is a rare and controversial entity, which has not yet been included in the current World Health Organization classification of odontogenic lesions. Owing to the small number of reported cases, the clinicopathological characteristics, biological behavior, prognosis, and appropriate treatment strategies for OCD remain to be defined. Herein, we present an additional case of OCD with a focus on the differential diagnosis and review of the pertinent literature, in order to enable better recognition by oral clinicians and pathologists and further characterization of this entity. CASE PRESENTATION: This paper reports a case of OCD in the posterior mandible of a 22-year-old female. Radiography showed a well-defined unilocular radiolucency with radiopaque materials. The intraoperative frozen section pathology gave a non-committed diagnosis of odontogenic neoplasm with uncertain malignant potential. Then a partial mandibulectomy with free iliac crest bone graft and titanium implants was performed. Microscopically, the tumor consisted of sheets, islands, and cords of round to polygonal epithelial cells associated with an abundant dentinoid matrix. Immunohistochemically, the tumor cells were diffusely positive for CK19, p63, and ß-catenin (cytoplasmic and nuclear). No rearrangement of the EWSR1 gene was detected. The final diagnosis was OCD. There has been no evidence of recurrence or metastasis for 58 months after surgery. We also provide a literature review of OCD cases, including one case previously reported as ghost cell odontogenic carcinoma from our hospital. CONCLUSIONS: OCD is a locally aggressive low grade malignancy without apparent metastatic potential. Wide surgical excision with clear margins and long-term period follow-up to identify any possible recurrence or metastases are recommended. Histopathological examination is essential to conclude the diagnosis. Special care must be taken to distinguish OCD from ghost cell odontogenic carcinoma and clear cell odontogenic carcinoma, as misdiagnosis might lead to unnecessary overtreatment. Study of additional cases is required to further characterize the clinicopathological features and clarify the nosologic status and biological behavior of this tumor.


Asunto(s)
Neoplasias Mandibulares , Tumores Odontogénicos , Femenino , Humanos , Adulto Joven , beta Catenina/análisis , Diagnóstico Diferencial , Queratina-19/análisis , Neoplasias Mandibulares/patología , Neoplasias Mandibulares/diagnóstico por imagen , Neoplasias Mandibulares/cirugía , Tumores Odontogénicos/patología , Tumores Odontogénicos/diagnóstico , Tumores Odontogénicos/diagnóstico por imagen , Tumores Odontogénicos/cirugía , Factores de Transcripción , Proteínas Supresoras de Tumor
16.
Mol Med ; 29(1): 73, 2023 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-37308812

RESUMEN

BACKGROUND: Elevated plasma homocysteine levels, known as hyperhomocysteinemia, have been identified as an independent risk factor for atherosclerosis and related cardiovascular diseases. Macrophage pyroptosis-mediated inflammation is crucial in the development of atherosclerosis, but the underlying mechanisms remain unclear. METHODS: A hyperhomocysteinemia atherosclerotic model with ApoE-/- mice fed with a high-methionine diet was constructed to investigate the role of plasma homocysteine in atherosclerosis. THP-1-derived macrophages were used to investigate the mechanisms by which Hcy regulates pyroptosis. RESULTS: We found that hyperhomocysteinemia resulted in larger atherosclerotic plaques and more secretion of inflammatory cytokines, while these effects were attenuated in Caspase-1 knockdown mice. Likewise, in vitro experiments demonstrated that treatment of macrophages with homocysteine resulted in NLRP3 inflammasome activation and pyroptosis, as evidenced by cleavage of Caspase-1, production of downstream IL-1ß, elevation of lactate dehydrogenase activity, and extensive propidium iodide-positive staining of cells. These were all inhibited by Caspase-1 inhibitor. In addition, excessive generation of reactive oxygen species was associated with mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential and ATP synthesis. Moreover, further experiments revealed that homocysteine induced endoplasmic reticulum stress, enhanced communication between the endoplasmic reticulum and mitochondria, and consequently contributed to calcium disorder. Furthermore, the endoplasmic reticulum stress inhibitor, 4PBA, the calcium chelator, BAPTA, and calcium channel inhibitor, 2-APB significantly improved macrophage pyroptosis. CONCLUSION: Homocysteine accelerates atherosclerosis progression by enhancing macrophages pyroptosis via promoting endoplasmic reticulum stress, endoplasmic reticulum-mitochondria coupling, and disturbing of calcium disorder.


Asunto(s)
Aterosclerosis , Hiperhomocisteinemia , Animales , Ratones , Piroptosis , Calcio , Caspasa 1 , Estrés del Retículo Endoplásmico
17.
Small ; 19(29): e2207785, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37052516

RESUMEN

Supramolecular rather than covalent molecular engineering on Feringa motors can provide an alternative toolkit for tuning the properties of motorized materials through appropriate supramolecular structural perturbations, which are underexplored. Herein, a multicomponent supramolecular gel system is successfully prepared by employing an ultra-low molecular weight gelator and a modulator-Feringa motor. The electron microscopic, spectroscopic, and rheological data revealed that the morphology and mechanical properties of the gel can be tuned via a crystallographic mismatch branching (CMB) mechanism simply by adding varied amounts of motor modulators. Notably, the rotary motion of the motor is preserved in such a multicomponent gel system, and the morphology and rheology of the gel can be further altered by the motor's rotary motion that promotes the structural perturbation, resulting in seldomly seen gel-to-gel transition events. The work shown here offers prospects to utilize a supramolecular perturbation strategy to deliver responsiveness from molecular motors to the corresponding bulk materials.

18.
Am Heart J ; 263: 159-168, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37327980

RESUMEN

BACKGROUND: Plaque rupture (PR) and plaque erosion (PE) are 2 distinct, different, and most common culprit lesion morphologies responsible for acute coronary syndrome (ACS). However, the prevalence, distribution, and characteristics of peripheral atherosclerosis in ACS patients with PR vs PE has never been studied. The aim of this study was to assess peripheral atherosclerosis burden and vulnerability evaluated by vascular ultrasound in ACS patients with coronary PR vs PE identified by optical coherence tomography (OCT). METHODS: Between October 2018 and December 2019, 297 ACS patients who underwent preintervention OCT examination of the culprit coronary artery were enrolled. Peripheral ultrasound examinations of carotid, femoral, and popliteal arteries were performed before discharge. RESULTS: Overall, 265 of 297 (89.2%) patients had at least one atherosclerotic plaque in a peripheral arterial bed. Compared with coronary PE, patients with coronary PR had a higher prevalence of peripheral atherosclerotic plaques (93.4% vs 79.1%, P < .001), regardless of location: carotid, femoral, or popliteal arteries. The number of peripheral plaques per patient was significantly larger in the coronary PR group than coronary PE (4 [2-7] vs 2 [1-5], P < .001). Additionally, there was a greater prevalence of peripheral vulnerable characteristics including plaque surface irregularity, heterogeneous plaque, and calcification in patients with coronary PR vs PE. CONCLUSIONS: Peripheral atherosclerosis exists commonly in patients presenting with ACS. Patients with coronary PR had greater peripheral atherosclerosis burden and more peripheral vulnerability compared to those with coronary PE, suggesting that comprehensive evaluation of peripheral atherosclerosis and multidisciplinary cooperative management maybe necessary, especially in patients with PR. TRIAL REGISTRATION: clinicaltrials.gov (NCT03971864).

19.
Opt Express ; 31(23): 38513-38528, 2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-38017955

RESUMEN

Optical communications at high bandwidth and high spectral efficiency rely on the use of a digital-to-analog converter (DAC). We propose the use of a neural network (NN) for digital pre-distortion (DPD) to mitigate the quantization and bandlimited impairments from a DAC in such systems. We experimentally validate our approach with a 64 Gbaud 8-level pulse amplitude modulation (PAM-8) signal. We examine the NN-DPD training with both direct and indirect learning methods. We compare the performance with typical Volterra, look-up table (LUT) and linear DPD solutions. We sweep regimes where nonlinear quantization becomes more prominent to highlight the advantages of NN-DPD. The proposed NN-DPD trained via direct learning outperforms the Volterra, LUT and linear DPDs by almost 0.9 dB, 1.9 dB and 2.9 dB, respectively. We find that an indirect learning recurrent NN offers better performance at the same complexity as Volterra, while a direct learning recursive NN pushes performance to a higher level than a Volterra can achieve.

20.
Opt Lett ; 48(18): 4829-4832, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37707913

RESUMEN

Recently, research about bound states in the continuum (BICs) has become more and more attractive. Nanostructures with rotational symmetry are usually utilized to realize polarization-independent quasi-BIC resonances. Here, we propose a new, to the best of our knowledge, scheme for a polarization-independent quasi-BIC without the help of rotational symmetry. With the rotation of the polarization direction of the incident light, a quasi-BIC resonance can be consistently observed in a dielectric cubic tetramer metasurface without rotational symmetry. Based on far-field multipolar decomposition and near-field electromagnetic distributions, it is found that different multipoles exhibit different dependences on the polarization direction, and the switch between electric and magnetic quadrupoles results in polarization-independent quasi-BIC resonance. Our findings provide an alternative scheme to design polarization-independent devices and promote wider potential applications.

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