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1.
Epilepsia Open ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38742825

RESUMO

OBJECTIVE: Closure surgery of patent foramen ovale (PFO) has been found to effectively control cryptogenic stroke and migraine, but it is uncertain whether PFO closure could also alleviate epileptic seizures. This study aims to observe the therapeutic effect of PFO closure on epileptic seizures. METHODS: Since July 11th, 2017, in the neurology department of West China Hospital, Sichuan University, Chengdu, we have been regularly monitoring patients with epilepsy who have undergone PFO closure. The patient's clinical information, such as frequency, duration, and severity of seizures, before and after surgery was recorded in detail as well as postoperative safety events. RESULTS: Of the 31 epilepsy patients who confirmed PFO observed (27 cases were drug-resistant epilepsy, 87.10%), average age of surgery was 23.74 years, and 12 cases were female (38.71%). After one-year follow-up, 26 patients (83.87%) achieved remission of seizure frequency, and 22 of whom (70.97%) experienced a remission of more than 50%. Additionally, compared to before surgery, 22 cases (70.97%) reported a decrease in the average seizure duration, and 20 cases (64.52%) reported a reduction in seizure severity. In the seizure indicators of frequency, average duration and severity, significant differences were identified between preoperative and postoperative comparisons with all test p values were <0.05. Furthermore, no serious safety events were reported except for one patient who briefly reported chest pain, and all patients expressed effective PFO closure. SIGNIFICANCE: The PFO closure has been shown for the first time to result in a significant reduction in the frequency, duration, and severity of seizures. Patients with drug-resistant epilepsy and PFO with a large shunt are ideal candidates for undergoing PFO closure. PLAIN LANGUAGE SUMMARY: Since PFO closure was found to have a good therapeutic effect on cryptogenic stroke and migraine, it has become a credible complementary therapy for the treatment of neurological diseases, and drug-resistant epilepsy with PFO is expected to become the next target disease that PFO closure could significantly improve.

2.
Korean J Radiol ; 25(5): 426-437, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685733

RESUMO

OBJECTIVE: Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with light-chain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. MATERIALS AND METHODS: In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49-63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At follow-up after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed. RESULTS: Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; P = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; P = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%-1.1%] vs. 1.7% [-5.5%-7.1%]; P = 0.017) and left ventricular ECV (-2.0% [-6.0%-1.3%] vs. 2.0% [-3.0%-5.0%]; P = 0.01) compared with those with inferior response. CONCLUSION: Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.


Assuntos
Cardiomiopatias , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Estudos de Viabilidade , Amiloidose/diagnóstico por imagem , Amiloidose/tratamento farmacológico , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico por imagem , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Resultado do Tratamento , Imagem Cinética por Ressonância Magnética/métodos , Antineoplásicos/uso terapêutico
3.
Plants (Basel) ; 13(6)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38592804

RESUMO

The carnivorous pitcher plants of the genus Nepenthes have long been known for their ethnobotanical applications. In this study, we prepared various extracts from the pitcher, stem, and leaf of Nepenthes miranda using 100% ethanol and assessed their inhibitory effects on key enzymes related to skin aging, including elastase, tyrosinase, and hyaluronidase. The cytotoxicity of the stem extract of N. miranda on H838 human lung carcinoma cells were also characterized by effects on cell survival, migration, proliferation, apoptosis induction, and DNA damage. The cytotoxic efficacy of the extract was enhanced when combined with the chemotherapeutic agent 5-fluorouracil (5-FU), indicating a synergistic effect. Flow cytometry analysis suggested that the stem extract might suppress H838 cell proliferation by inducing G2 cell cycle arrest, thereby inhibiting carcinoma cell proliferation. Gas chromatography-mass spectrometry (GC-MS) enabled the tentative identification of the 15 most abundant compounds in the stem extract of N. miranda. Notably, the extract showed a potent inhibition of the human RPA32 protein (huRPA32), critical for DNA replication, suggesting a novel mechanism for its anticancer action. Molecular docking studies further substantiated the interaction between the extract and huRPA32, highlighting bioactive compounds, especially the two most abundant constituents, stigmast-5-en-3-ol and plumbagin, as potential inhibitors of huRPA32's DNA-binding activity, offering promising avenues for cancer therapy. Overall, our findings position the stem extract of N. miranda as a promising source of natural compounds for anticancer therapeutics and anti-skin-aging treatments, warranting further investigation into its molecular mechanisms and potential clinical applications.

4.
Environ Sci Pollut Res Int ; 31(21): 31511-31523, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38632201

RESUMO

COVID-19 has been a significant global concern due to its contagious nature. In May 2021, Taiwan experienced a severe outbreak, leading the government to enforce strict Pandemic Alert Level 3 restrictions in order to curtail its spread. Although previous studies in Taiwan have examined the effects of these measures on air quality, further research is required to compare different time periods and assess the health implications of reducing particulate matter during the Level 3 lockdown. Herein, we analyzed the mass concentrations, chemical compositions, seasonal variations, sources, and potential health risks of PM1.0 and PM2.5 in Central Taiwan before and during the Level 3 lockdown. As a result, coal-fired boilers (47%) and traffic emissions (53%) were identified as the predominant sources of polycyclic aromatic hydrocarbons (PAHs) in PM1.0, while in PM2.5, the dominant sources of PAHs were coal-fired boilers (28%), traffic emissions (50%), and iron and steel sinter plants (22.1%). Before the pandemic, a greater value of 20.9 ± 6.92 µg/m3 was observed for PM2.5, which decreased to 15.3 ± 2.51 µg/m3 during the pandemic due to a reduction in industrial and anthropogenic emissions. Additionally, prior to the pandemic, PM1.0 had a contribution rate of 79% to PM2.5, which changed to 89% during the pandemic. Similarly, BaPeq values in PM2.5 exhibited a comparable trend, with PM1.0 contributing 86% and 65% respectively. In both periods, the OC/EC ratios for PM1.0 and PM2.5 were above 2, due to secondary organic compounds. The incremental lifetime cancer risk (ILCR) of PAHs in PM2.5 decreased by 4.03 × 10-5 during the pandemic, with PM1.0 contributing 73% due to reduced anthropogenic activities.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Monitoramento Ambiental , Material Particulado , Estações do Ano , Taiwan/epidemiologia , Material Particulado/análise , COVID-19/epidemiologia , Poluentes Atmosféricos/análise , Humanos , Poluição do Ar/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , SARS-CoV-2 , Pandemias
5.
J Pharm Biomed Anal ; 241: 116000, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38280234

RESUMO

An increasing number of drug research institutions consider genotoxic impurity research a core task in drug research and development. Peroxides in drugs may directly or indirectly attack and damage cell DNA, posing a potential carcinogenic risk to the human body. Currently, the literature only studies hydroperoxide impurities, and benzyl peroxide has not been studied yet. In this study, an effective method for ultra-performance liquid chromatographymass spectrometry (UPLCMS/MS) was established and verified to detect and quantify the potential genotoxic impurity (PGI), empagliflozin benzyl peroxide, in metformin-empagliflozin combination formulations, which has not been reported thus far. A Waters ACQUITY UPLC HSS T3 (3.0 ×100 mm, 1.8 µm) column was used to achieve chromatographic separation with gradient elution. The mass spectrometry conditions were optimized using electrospray ionization in the negative mode. Following the International Conference of Harmonization (ICH) guidelines, this methodology can quantify PGIs at 1.35 ng/mL (5.4 ppm) in samples. This validated method exhibited good linearity over a concentration range of 5.4 to 36 ppm, and the accuracy of this method was in the range of 83.2-95.0% for empagliflozin benzyl peroxide. This approach fills the gap in the detection method for benzyl peroxide impurities in metformin hydrochloride and empagliflozin tablets, providing technical support for the quality control of the drug.


Assuntos
Compostos Benzidrílicos , Glucosídeos , Metformina , Humanos , Metformina/análise , Cromatografia Líquida de Alta Pressão/métodos , Análise Espectral , Comprimidos , Peróxidos
6.
Rheumatology (Oxford) ; 63(4): 1172-1179, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-37094178

RESUMO

OBJECTIVE: Myocardial fibrosis occurs in the early subclinical stage of cardiac involvement in idiopathic inflammatory myopathies (IIMs). Soluble suppression of tumorigenicity 2 (sST2) is known to have an immunomodulatory impact during autoimmune disease development. The current study investigated the diagnostic value of sST2 for myocardial fibrosis during early stage of cardiac involvement in IIM. METHODS: A total of 44 IIM patients with normal heart function and 32 age- and gender-matched healthy controls (HCs) were enrolled. Serum sST2 levels were measured by ELISA and cardiac magnetic resonance (CMR) parameters for myocardial fibrosis [native T1, extracellular volume (ECV), late-gadolinium enhancement (LGE)] and oedema (T2 values) were analysed. RESULTS: IIM patients had significantly higher sST2 levels than HCs [67.5 ng/ml (s.d. 30.4)] vs 14.4 (5.5), P < 0.001] and levels correlated positively with diffuse myocardial fibrosis parameters, native T1 (r = 0.531, P = 0.000), ECV (r = 0.371, P = 0.013) and focal myocardial fibrosis index and LGE (r = 0.339, P = 0.024) by Spearman's correlation analysis. sST2 was an independent predictive factor for diffuse and focal myocardial fibrosis after adjustment for age, gender, BMI and ESR. Risk increased ≈15.4% for diffuse [odds ratio (OR) 1.154 (95% CI 1.021, 1.305), P = 0.022] and 3.8% for focal [OR 1.038 (95% CI 1.006, 1.072), P = 0.020] myocardial fibrosis per unit increase of sST2. Cut-off values for diagnosing diffuse and focal myocardial fibrosis were sST2 ≥51.3 ng/ml [area under the curve (AUC) = 0.942, sensitivity = 85.7%, specificity = 98.9%, P < 0.001] and 53.3 ng/ml (AUC = 0.753, sensitivity = 87.5%, specificity = 58.3%, P < 0.01), respectively. CONCLUSION: sST2 showed a marked elevation during the subclinical stage of cardiac involvement in IIM and has potential as a biomarker for predicting diffuse and focal myocardial fibrosis in IIM.


Assuntos
Cardiomiopatias , Miosite , Humanos , Meios de Contraste , Gadolínio , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/etiologia , Fibrose
7.
J Epidemiol ; 34(2): 87-93, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36908115

RESUMO

BACKGROUND: Ambient particulate matter is classified as a human Class 1 carcinogen, and recent studies found a positive relationship between fine particulate matter (PM2.5) and liver cancer. Nevertheless, little is known about which specific metal constituent contributes to the development of liver cancer. OBJECTIVE: To evaluate the association of long-term exposure to metal constituents in PM2.5 with the risk of liver cancer using a Taiwanese cohort study. METHODS: A total of 13,511 Taiwanese participants were recruited from the REVEAL-HBV in 1991-1992. Participants' long-term exposure to eight metal constituents (Ba, Cu, Mn, Sb, Zn, Pb, Ni, and Cd) in PM2.5 was based on ambient measurement in 2002-2006 followed by a land-use regression model for spatial interpolation. We ascertained newly developed liver cancer (ie, hepatocellular carcinoma [HCC]) through data linkage with the Taiwan Cancer Registry and national health death certification in 1991-2014. A Cox proportional hazards model was utilized to assess the association between exposure to PM2.5 metal component and HCC. RESULTS: We identified 322 newly developed HCC with a median follow-up of 23.1 years. Long-term exposure to PM2.5 Cu was positively associated with a risk of liver cancer. The adjusted hazard ratio (HR) was 1.13 (95% confidence interval [CI], 1.02-1.25; P = 0.023) with one unit increment on Cu normalized by PM2.5 mass concentration in the logarithmic scale. The PM2.5 Cu-HCC association remained statistically significant with adjustment for co-exposures to other metal constituents in PM2.5. CONCLUSION: Our findings suggest PM2.5 containing Cu may attribute to the association of PM2.5 exposure with liver cancer.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/epidemiologia , Estudos de Coortes , Carcinoma Hepatocelular/epidemiologia , Vírus da Hepatite B , Japão , Material Particulado/efeitos adversos , Metais , Exposição Ambiental/efeitos adversos
8.
Biomed Chromatogr ; 38(2): e5790, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38158853

RESUMO

In the production of doxofylline, the common occurrence of toxic p-toluene sulfonate generation prompted the development and validation of a method using HPLC with ultraviolet detection (HPLC-UV). This method is designed for detecting four potential genotoxic impurities (PGIs) present in both doxofylline drug substance and tablets, with a focus on the UV-absorbing group p-toluene sulfonate. The four impurities were methyl 4-methylbenzenesulfonate (PGI-1), ethyl 4-methylbenzenesulfonate (PGI-2), 2-hydroxyethyl 4-methylbenzenesulfonate (PGI-3), and 2-(4-methylphenyl)sulfonyloxyethyl 4-methylbenzenesulfonate (PGI-4). In this method, chromatographic separation was achieved using a Waters Symmetry C18 column (250 mm × 4.6 mm, 5 µm). The mobile phases consisted of 20% acetonitrile as mobile phase A and pure acetonitrile as mobile phase B, operating in gradient elution mode at a flow rate of 1.0 mL/min. According to the guidelines of the International Conference on Harmonization, it was determined that this method could quantify four PGIs at 0.0225 µg/mL in samples containing 60 mg/mL. The validated approach demonstrated excellent linearity (R2 > 0.999) across the concentration range of 30%-200% (relative to 0.075 µg/mL doxofylline) for the four PGIs. The accuracy of this method for the four PGIs ranged from 94.8% to 100.4%. The reverse-phase-HPLC-UV analytical method developed in this study is characterized by its speed and precision, making it suitable for the sensitive analysis of benzene sulfonate PGIs in doxofylline drug substances and tablets.


Assuntos
Benzeno , Benzenossulfonatos , Princípios Ativos , Teofilina/análogos & derivados , Cromatografia Líquida de Alta Pressão/métodos , Comprimidos/química , Acetonitrilas
9.
Sci Total Environ ; 912: 169428, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38104815

RESUMO

Wearing masks to prevent infectious diseases, especially during the COVID-19 pandemic, is common. However, concerns arise about inhalation exposure to microplastics (MPs) when disposable masks are improperly reused. In this study, we assessed whether disposable masks release inhalable MPs when reused in simulated wearing conditions. All experiments were conducted using a controlled test chamber setup with a constant inspiratory flow. Commercially available medical masks with a three-layer material, composition comprising polypropylene (PP in the outer and middle layers) and polyethylene (PE in the inner layer), were used as the test material. Brand-new masks with and without hand rubbing, as well as reused medical masks, were tested. Physical properties (number, size, and shape) and chemical composition (polymers) were identified using various analytical techniques such as fluorescence staining, fluorescence microscopy, and micro-Fourier Transform Infrared Spectroscopy (µFTIR). Scanning Electron Microscopy (SEM) was used to scrutinize the surface structure of reused masks across different layers, elucidating the mechanism behind the MP generation. The findings revealed that brand-new masks subjected to hand rubbing exhibited a higher cumulative count of MPs, averaging approximately 1.5 times more than those without hand rubbing. Fragments remained the predominant shape across all selected size classes among the released MPs from reused masks, primarily through a physical abrasion mechanism, accounting for >90 % of the total MPs. The numbers of PE particles were higher than PP particles, indicating that the inner layer of the mask contributed more inhalable MPs than the middle and outer layers combined. The released MPs from reused masks reached their peak after 8 h of wearing. This implies that regularly replacing masks serves as a preventive measure and mitigates associated health risks of inhalation exposure to MPs.


Assuntos
Exposição por Inalação , Poluentes Químicos da Água , Humanos , Exposição por Inalação/prevenção & controle , Máscaras , Microplásticos , Pandemias , Plásticos , Polietileno
10.
J Magn Reson Imaging ; 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37972587

RESUMO

BACKGROUND: First-pass perfusion cardiac MR imaging could reflect pulmonary hemodynamics. However, the clinical value of pulmonary transit time (PTT) derived from first-pass perfusion MRI in light-chain (AL) amyloidosis requires further evaluation. PURPOSE: To assess the clinical and prognostic value of PTT in patients with AL amyloidosis. STUDY TYPE: Prospective observational study. POPULATION: 226 biopsy-proven systemic AL amyloidosis patients (age 58.62 ± 10.10 years, 135 males) and 43 healthy controls (age 42 ± 16.2 years, 20 males). FIELD STRENGTH/SEQUENCE: SSFP cine and phase sensitive inversion recovery late gadolinium enhancement (LGE) sequences, and multislice first-pass myocardial perfusion imaging with a saturation recovery turbo fast low-angle shot (SR-TurboFLASH) pulse sequence at 3.0T. ASSESSMENT: PTT was measured as the time interval between the peaks of right and left ventricular cavity arterial input function curves on first-pass perfusion MR images. STATISTICAL TESTS: Independent-sample t test, Mann-Whitney U test, Chi-square test, Fisher's exact test, analysis of variance, or Kruskal-Wallis test, as appropriate; univariable and multivariable Cox proportional hazards models and Kaplan-Meier curves, area under receiver operating characteristic curve were used to determine statistical significance. RESULTS: PTT could differentiate AL amyloidosis patients with (N = 188) and without (N = 38) cardiac involvement (area under the curve [AUC] = 0.839). During a median follow-up of 35 months, 160 patients (70.8%) demonstrated all-cause mortality. After adjustments for clinical (Hazard ratio [HR] 1.061, confidence interval [CI]: 1.021-1.102), biochemical (HR 1.055, CI: 1.014-1.097), cardiac MRI-derived (HR 1.077, CI: 1.034-1.123), and therapeutic (HR 1.063, CI: 1.024-1.103) factors, PTT predicted mortality independently in patients with AL amyloidosis. Finally, PTT could identify worse outcomes in patients demonstrating New York Heart Association class III, Mayo 2004 stage III, and transmural LGE pattern. DATA CONCLUSION: PTT may serve as a new imaging predictor of cardiac involvement and prognosis in AL amyloidosis. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

11.
Acta Cardiol ; : 1-8, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37768132

RESUMO

BACKGROUND: This study aimed to report the genotypes and phenotypes of hereditary transthyretin cardiac amyloidosis (hATTR-CA) in a Western Chinese cohort and review the genetic profiles of this disorder in the Chinese population. METHODS: Transthyretin (TTR) gene sequencing of probands diagnosed with TTR cardiac amyloidosis and their relatives was performed at West China Hospital of Sichuan University from January 2018 to December 2021. All patients underwent endomyocardial biopsy for light and electron microscopy examinations. Clinical and essential examination materials were retrospectively collected and analysed. RESULTS: TTR gene alteration was demonstrated in five probands and their two relatives. Three TTR variants were identified, namely, Ser23Asn, Glu54Leu and Thr60Ala. This study is the first to report Glu54Leu as pathogenic mutations in Chinese hATTR-CA patients. The Ser23Asn mutation was the most common mutation in this cohort. Five probands, including two males and three females, were all ethnic Han-Chinese. The median age at diagnosis and delay in diagnosis (interval from onset to diagnosis) was 56 years (range, 54-69 years) and 8 years (range, from 1 to 30 years), respectively. Three cases showed a defined family history of amyloidosis. Endomyocardial biopsies and TTR immunohistochemistry showed positive results in all patients. Two probands died 17.0 months and 21.0 months after diagnosis. CONCLUSIONS: We identified one novel TTR variants causing hATTR-CA in the West Han Chinese population. To avoid misdiagnosis or delayed diagnosis of hATTR-CA, TTR genotypic screening and endomyocardial biopsy should be performed as soon as possible in cases with heightened clinical suspicion.

12.
Environ Sci Pollut Res Int ; 30(45): 101627-101636, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37653197

RESUMO

Schoolchildren are sensitive to airborne aldehyde exposures. The knowledge regarding inhalation exposure to aldehydes and the factors influencing exposure in schoolchildren is limited. This study aimed to assess the variability and potential health risks of exposure to aldehydes (including formaldehyde) in schoolchildren. The important factors affecting personal exposure to aldehydes were also explored. Forty schoolchildren were recruited from the urban and suburban areas of Taiwan for aldehyde samplings and questionnaire surveys. Personal and indoor home samples of aldehydes were collected simultaneously during warm and cold seasons. We also identified the potential variables associated with aldehyde exposure based on the participant's responses to the questionnaires using mixed-effects models. The dominant three abundant aldehydes identified in personal exposure samples were formaldehyde (geometric mean, GM = 12.2 µg/m3), acetaldehyde (GM = 5.53 µg/m3), and hexaldehyde (GM = 8.79 µg/m3), accounting for approximately 80% of the total selected aldehydes. Higher personal exposure to aldehydes was observed during the warm season. Moreover, the within-subject variance was predominant, accounting for 66.6 to > 99.9% of the total variance in exposure. Schoolchildren had a high probability of overexposure to formaldehyde and acrolein, which resulted in an incremental lifetime cancer risk of 1.59 × 10-4 (95th percentile = 4.64 × 10-4). Season, location, household refurbishment, and indoor ventilation variables were significantly associated with personal exposure to aldehydes. The results can improve our understanding of aldehyde exposure among schoolchildren to propose mitigation strategies. These findings may be applied to further epidemiological studies.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Humanos , Criança , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Aldeídos/análise , Formaldeído/análise , Inquéritos e Questionários
13.
MedComm (2020) ; 4(4): e334, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37576864

RESUMO

Patent foramen ovale (PFO) is a congenital defect in the partition between two atria, which may cause right-to-left shunt (RLS), leading to neurological chronic diseases with episodic manifestations (NCDEMs), such as migraine and epilepsy. However, whether PFO closure was effective in improving NCDEMs and the mechanism were unclear. Twenty-eight patients with migraine or epilepsy who underwent PFO closure were recruited. Notably, approximately half of patients received 50% or more reduction in seizure or headache attacks. Meanwhile, the postoperative blood oxygen partial pressure and oxygen saturation were elevated after PFO closure. Multisite (peripheral, right, and left atrial) and multitimepoint (before and after surgery) plasma proteomics from patients showed that the levels of free hemoglobin and cell adhesion molecules (CAMs) were significantly increased after PFO closure, which may be related to the relief of the hypoxic state. Furtherly, the omics data from multiple brain regions of mice revealed that a large number of proteins were differentially expressed in the occipital region in response to PFO, including redox molecules and CAMs, suggesting PFO-caused hypoxia may have great impacts on occipital region. Collectively, PFO may cause NCDEMs due to RLS-induced hypoxia, and PFO closure could prevent RLS to improve migraine and epilepsy.

14.
J Cardiovasc Magn Reson ; 25(1): 37, 2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37349765

RESUMO

BACKGROUND: There is a paucity of quantitative measurements of cardiac tumors and myocardium using parametric mapping techniques. This study aims to explore quantitative characteristics and diagnostic performance of native T1, T2, and extracellular volume (ECV) values of cardiac tumors and left ventricular (LV) myocardium. METHODS: Patients with suspected cardiac tumors who underwent cardiovascular magnetic resonance (CMR) between November 2013 and March 2021 were prospectively enrolled. The diagnoses of primary benign or malignant tumors were based on pathologic findings if available, comprehensive medical history evaluations, imaging, and long-term follow-up data. Patients with pseudo-tumors, cardiac metastasis, primary cardiac diseases, and prior radiotherapy or chemotherapy were excluded. Multiparametric mapping values were measured on both cardiac tumors and the LV myocardium. Statistical analyses were performed using independent-samples t-test, receiver operating characteristic, and Bland-Altman analyses. RESULTS: A total of 80 patients diagnosed with benign (n = 54), or primary malignant cardiac tumors (n = 26), and 50 age and sex-matched healthy volunteers were included. Intergroup differences in the T1 and T2 values of cardiac tumors were not significant, however, patients with primary malignant cardiac tumors showed significantly higher mean myocardial T1 values (1360 ± 61.4 ms) compared with patients with benign tumors (1259.7 ± 46.2 ms), and normal controls (1206 ± 44.0 ms, all P < 0.05) at 3 T. Patients with primary malignant cardiac tumors also showed significantly higher mean ECV (34.6 ± 5.2%) compared with patients with benign (30.0 ± 2.5%) tumors, and normal controls (27.3 ± 3.0%, all P < 0.05). For the differentiation between primary malignant and benign cardiac tumors, the mean myocardial native T1 value showed the highest efficacy (AUC: 0.919, cutoff value: 1300 ms) compared with mean ECV (AUC: 0.817) and T2 (AUC: 0.619) values. CONCLUSION: Native T1 and T2 of cardiac tumors showed high heterogeneity, while myocardial native T1 values in primary malignant cardiac tumors were elevated compared to patients with benign cardiac tumors, which may serve as a new imaging marker for primary malignant cardiac tumors.


Assuntos
Neoplasias Cardíacas , Imagem Cinética por Ressonância Magnética , Humanos , Estudos de Casos e Controles , Valor Preditivo dos Testes , Miocárdio/patologia , Imageamento por Ressonância Magnética , Neoplasias Cardíacas/diagnóstico por imagem , Meios de Contraste
15.
Sci Total Environ ; 880: 163275, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37028680

RESUMO

The Coronavirus Disease 2019 (COVID-19) pandemic provided an unprecedented natural experiment, that allowed us to investigate the impacts of different restrictive measures on personal exposure to specific volatile organic compounds (VOCs) and aldehydes and resulting health risks in the city. Ambient concentrations of the criteria air pollutants were also evaluated. Passive sampling for VOCs and aldehydes was conducted for graduate students and ambient air in Taipei, Taiwan, during the Level 3 warning (strict control measures) and Level 2 alert (loosened control measures) of the COVID-19 pandemic in 2021-2022. Information on the daily activities of participants and on-road vehicle counts nearby the stationary sampling site during the sampling campaigns were recorded. Generalized estimating equations (GEE) with adjusted meteorological and seasonal variables were used to estimate the effects of control measures on average personal exposures to the selected air pollutants. Our results showed that ambient CO and NO2 concentrations in relation to on-road transportation emissions were significantly reduced, which led to an increase in ambient O3 concentrations. Exposure to specific VOCs (benzene, methyl tert-butyl ether (MTBE), xylene, ethylbenzene, and 1,3-butadiene) associated with automobile emissions were remarkably decreased by ~40-80 % during the Level 3 warning, resulting in 42 % and 50 % reductions of total incremental lifetime cancer risk (ILCR) and hazard index (HI), respectively, compared with the Level 2 alert. In contrast, the exposure concentration and calculated health risks in the selected population for formaldehyde increased by ~25 % on average during the Level 3 warning. Our study improves knowledge of the influence of a series of anti-COVID-19 measures on personal exposure to specific VOCs and aldehydes and its mitigations.


Assuntos
Poluentes Atmosféricos , COVID-19 , Compostos Orgânicos Voláteis , Humanos , Aldeídos/análise , Compostos Orgânicos Voláteis/análise , Pandemias , COVID-19/epidemiologia , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos
16.
Nano Lett ; 23(7): 2502-2510, 2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-36926974

RESUMO

Self-propelled micro/nanomotors are emergent intelligent sensors for analyzing extracellular biomarkers in circulating biological fluids. Conventional luminescent motors are often masked by a highly dynamic and scattered environment, creating challenges to characterize biomarkers or subtle binding dynamics. Here we introduce a strategy to amplify subtle signals by coupling strong light-matter interactions on micromotors. A smart whispering-gallery-mode microlaser that can self-propel and analyze extracellular biomarkers is demonstrated through a liquid crystal microdroplet. Lasing spectral responses induced by cavity energy transfer were employed to reflect the abundance of protein biomarkers, generating exclusive molecular labels for cellular profiling of exosomes derived from 3D multicellular cancer spheroids. Finally, a microfluidic biosystem with different tumor-derived exosomes was employed to elaborate its sensing capability in complex environments. The proposed autonomous microlaser exhibits a promising method for both fundamental biological science and applications in drug screening, phenotyping, and organ-on-chip applications.


Assuntos
Vesículas Extracelulares , Neoplasias , Humanos , Luminescência , Microfluídica
17.
Int J Cardiovasc Imaging ; 39(5): 1055-1064, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36840896

RESUMO

To explore whether contrast agent administration will affect ventricular volume and strain parameters measured on cardiac magnetic resonance cine images. This prospective study enrolled 88 patients, including 32 patients with cardiac amyloidosis (CA), 32 patients with hypertrophic cardiomyopathy (HCM), and 24 control participants, to perform steady-state free precession (SSFP)-cine imaging twice, respectively before and after contrast agent injection. Indexed left and right ventricular (LV and RV) volume and LV strain parameters (peak radial strain [PRS], peak circumferential strain [PCS], peak longitudinal strain [PLS]) were analyzed and compared between the pre- and post-contrast cine groups. Compared to the group of pre-contrast cine, the end-diastolic volume index (EDVi) and end-systolic volume index (ESVi) significantly increased in the group using post-contrast cine images (all p < 0.05), especially in the right ventricle. After contrast injection, the right ventricular ejection fraction (RVEF) decreased significantly (p < 0.05), while the left ventricular ejection fraction (LVEF) only reduced for patients with HCM (p < 0.05). The PRS (37.1 ± 15.2 vs. 32.0 ± 15.4, p < 0.001) and PCS (- 14.9 ± 4.3 vs. - 14.0 ± 4.1, p < 0.001) derived from post-contrast cine images reduced significantly in all patients and this tendency remained in subgroup analysis except for PCS in the control group. The administration of a contrast agent may influence the measurements of ventricular volume and strain. Acquiring pre-contrast cine images were suggested for patients who required more accurate right ventricle evaluation or precise strain assessment.


Assuntos
Meios de Contraste , Função Ventricular Esquerda , Humanos , Volume Sistólico , Estudos Prospectivos , Valor Preditivo dos Testes , Função Ventricular Direita , Imageamento por Ressonância Magnética , Imagem Cinética por Ressonância Magnética/métodos , Ventrículos do Coração/diagnóstico por imagem
18.
Sci Total Environ ; 870: 161733, 2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-36682561

RESUMO

Submicron and ultrafine particle (UFP) exposure may be epidemiologically and toxicologically linked to pulmonary, neurodegenerative, and cardiovascular diseases. This study explores UFP and fine particle sources using a positive matrix factorization (PMF) model based on PM2.5 chemical compositions and particle number size distributions (PNSDs). The particle chemical composition and size distribution contributions are simultaneously identified to evaluate lung deposition and excess cancer risks. High correlations between the PNSD and chemical composition apportionment results were observed. Fresh and aged traffic particles dominated the number concentrations, while heterogeneous, photochemical reactions and/or regional transport may have resulted in secondary aerosol formation. Fresh and aged road traffic particle sources mostly contributed to the lung deposition dosage in the pulmonary region (~53 %), followed by the tracheobronchial (~30.4 %) and head regions (~16.6 %). However, lung-deposited surface area (LDSA) concentrations were dominated by aged road traffic (~39.2 %) and secondary aerosol (~33.2 %) sources. The excess cancer risks caused by Cr6+, Ni, and As were also mainly contributed to by aged road traffic (~31.7 %) and secondary aerosols (~67 %). The source apportionments based on the physical and chemical properties of aerosol particles are complementary, offering a health impact benchmark of UFPs in a Southeast Asia urban city.


Assuntos
Poluentes Atmosféricos , Neoplasias , Humanos , Idoso , Material Particulado/análise , Poluentes Atmosféricos/análise , Tamanho da Partícula , Monitoramento Ambiental , Pulmão , Aerossóis/análise
19.
Chem Biol Interact ; 369: 110294, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36460127

RESUMO

BACKGROUND: Liver ischemia-reperfusion injury (IRI) is a major complication in the perioperative period and often leads to liver failure and even systemic inflammation. Previous studies have suggested that the inflammatory response participated in the liver damage during liver IRI. Nicotinamide phosphoribosyl transferase (NAMPT) is required for the maintenance of cellular nicotinamide adenine dinucleotide (NAD+) levels, catalyzing the rate-limiting step in the NAD + salvage pathway. NAMPT is strongly upregulated during inflammation and constitutes an important mechanistic link between inflammatory, metabolic, and transcriptional pathways. The aim of our study was to investigate the role of NAMPT in liver IRI. METHODS: We investigated the effect of pharmacological inhibition of NAMPT with FK866 in models of liver IRI. Liver damage was assessed by HE staining, serum ALT/AST, and TUNEL staining. To examine the mechanism, primary hepatocytes, liver macrophages and RAW264.7 cells were treated with or without NAMPT inhibitors before hypoxia-reoxygenation. Liver macrophages and RAW 264.7 cells activation in vitro was evaluated by western blotting, flow cytometry, and ELISA. RESULT: We found that NAMPT was upregulated in liver IRI. Treatment with the NAMPT inhibitor FK866 ameliorated liver IRI and suppressed inflammation in mice. Although NAMPT plays an important role both in hepatocytes and liver macrophages, we focused on the impact of NAMPT on liver macrophages. The mechanism revealed that FK866 potently inhibited NAMPT activity, as demonstrated by reduced liver NAD+ and intracellular NAD+, resulting in reduced abundance and activity of NAD + -dependent enzymes, including poly (ADP-ribose) polymerase 1 (PARP1), thus inhibiting macrophage M1 polarization by reducing CD86, iNOS, TNF-α, and interleukin (IL)-1ß. Taken together, our data suggested that NAMPT can regulate macrophage polarization through NAD+/PARP1 to ameliorate liver injury, and that FK866-mediated NAMPT blockade may be a therapeutic approach in liver IRI.


Assuntos
NAD , Traumatismo por Reperfusão , Camundongos , Animais , NAD/metabolismo , Citocinas/metabolismo , Fígado/metabolismo , Macrófagos/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo
20.
Nano Lett ; 22(22): 8949-8956, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36367840

RESUMO

Amyloidogenesis is a critical hallmark for many neurodegenerative diseases and drug screening; however, identifying intermediate states of protein aggregates at an earlier stage remains challenging. Herein, we developed a peptide-encapsulated droplet microlaser to monitor the amyloidogenesis process and evaluate the efficacy of anti-amyloid drugs. The lasing wavelength changes accordingly with the amyloid peptide folding behaviors and nanostructure conformations in the droplet resonator. A 3D deep-learning strategy was developed to directly image minute spectral shifts through a far-field camera. By extracting 1D color information and 2D features from the laser images, the progression of the amyloidogenesis process could be monitored using arrays of laser images from microdroplets. The training set, validation set, and test set of the multimodal learning model achieved outstanding classification accuracies of over 95%. This study shows the great potential of deep-learning-empowered peptide microlaser yields for protein misfolding studies and paves the way for new possibilities for high-throughput imaging of cavity biosensing.


Assuntos
Amiloidose , Aprendizado Profundo , Humanos , Imageamento Tridimensional/métodos , Amiloide/metabolismo , Amiloidose/metabolismo
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