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1.
Front Neurosci ; 18: 1455131, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39224578

RESUMEN

Background: Patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis often experience severe symptoms. Resting-state functional MRI (rs-fMRI) has revealed widespread impairment of functional networks in patients. However, the changes in information flow remain unclear. This study aims to investigate the intrinsic functional connectivity (FC) both within and between resting-state networks (RSNs), as well as the alterations in effective connectivity (EC) between these networks. Methods: Resting-state functional MRI (rs-fMRI) data were collected from 25 patients with anti-NMDAR encephalitis and 30 healthy controls (HCs) matched for age, sex, and educational level. Changes in the intrinsic functional connectivity (FC) within and between RSNs were analyzed using independent component analysis (ICA). The functional interaction between RSNs was identified by granger causality analysis (GCA). Results: Compared to HCs, patients with anti-NMDAR encephalitis exhibited lower performance on the Wisconsin Card Sorting Test (WCST), both in terms of correct numbers and correct categories. Additionally, these patients demonstrated decreased scores on the Montreal Cognitive Assessment (MoCA). Neuroimaging studies revealed abnormal intra-FC within the default mode network (DMN), increased intra-FC within the visual network (VN) and dorsal attention network (DAN), as well as increased inter-FC between VN and the frontoparietal network (FPN). Furthermore, aberrant effective connectivity (EC) was observed among the DMN, DAN, FPN, VN, and somatomotor network (SMN). Conclusion: Patients with anti-NMDAR encephalitis displayed noticeable deficits in both memory and executive function. Notably, these patients exhibited widespread impairments in intra-FC, inter-FC, and EC. These results may help to explain the pathophysiological mechanism of anti-NMDAR encephalitis.

2.
Chemistry ; : e202402199, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39117600

RESUMEN

Isoindigo, an electron-withdrawing building block for polymeric field-effect transistors, has long been considered to be non-fluorescent. Moreover, using electron-deficient heterocycle to replace the phenyl ring in the isoindigo core for better electron transport behaviour is synthetically challenging. Here we report the syntheses of a series of tetraazaisoindigos, including pyrazinoisoindigo (PyrII), pyrimidoisoindigo (PymII) and their hybrid (PyrPymII), and the investigation on their photophysical and electric properties. Proper flanking groups need to be chosen to stabilize these highly electron-deficient bislactams. Both PyrII and PymII derivatives show lower LUMO energy levels than that of naphthalene bisimide (NDI). Interestingly, PyrII is instinctively unstable and can be easily reduced, while both PymII derivatives are stable. More surprisingly, PymII derivatives are highly fluorescent and their photoluminescence quantum yields are around 40%, 133 times higher than that of reported isoindigo derivatives. UV-vis spectroscopic results and theoretical calculations show that strong intramolecular hydrogen-bond exists in PymII, which prohibits it from non-radiative decay and accounts for its fluorescent behaviour.  PymII deriviatives are n-type semiconductors, while Ph-PyrII and the hybrid show balanced ambipolar charge transport behaviour, all among the best isoindigo derivatives. Our study not only discloses the structure-property relationship of tetraazaisoindigos, but also provides electron-deficient monomers for conjugated polymers.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39208026

RESUMEN

BACKGROUND: We investigated clinical characteristics and prostate cancer (PCa) survival patterns among Latino patients considering nativity compared to non-Latino Black (NLB) and non-Latino White (NLW) patients. METHODS: We used data from the California Cancer Registry (1995-2021), which included 347,540 NLW, 50,032 NLB, and 75,238 Latino PCa patients. Frequencies of sociodemographic and clinical variables were assessed with Chi-square tests. Multivariable regression models were fitted to evaluate determinants of treatment reception, Gleason upgrade, and survival differences. Exploratory analyses were conducted grouping Latino cases into US-born and non-US-born by country-of-origin. RESULTS: Compared to NLW, NLB cases had the greatest proportion of younger patients, whereas non-US-born Latino patients had the greatest proportion of low socio-economic status and uninsured patients. Non-US-born Latinos showed greater proportion of diagnoses completed with <6 core biopsies, Gleason >8, stage IV tumors and metastasis. Multivariable analyses showed that compared to NLW, Latino patients were as likely to receive treatment, whereas NLB cases were less likely (OR = 0.81, 95% CI: 0.67-0.98, p = 0.029). Compared to NLW, Non-US-born Latino cases were less likely to die of PCa (HR = 0.78; 95% CI = 0.64-0.94, p=0.011), with no difference reported for NLB cases. CONCLUSIONS: Considering sociodemographic and clinical characteristics, non-US-born Latino PCa patients had better survival than NLW. This highlights the need to identify key determinants of these survival differences, and the importance of sociodemographic and clinical determinants in survival disparities. IMPACT: Our study emphasizes the importance of considering nativity among Latino patients to understand PCa disparities and outcomes in this population.

5.
Sci Total Environ ; 951: 175392, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39122037

RESUMEN

Phytoplankton growth in freshwater is often limited by the availability of phosphorus (P), and thorough understandings of P availability are essential to prevent algal blooms. However, the differences in bioavailability and utilization mechanisms of different P forms remain unclear, especially whether organophosphorus could be used as P sources. This study investigated the effects of 0.5, 1.0, and 2.0 mg/L P on Microcystis aeruginosa, including dissolved organic P (DOP) (1-hydroxyethane 1,1-diphosphonic acid) and dissolved inorganic P (DIP) (dipotassium phosphate). Compared with DIP, intracellular P content absorbed in DOP treatment was significantly lower. DOP was more conducive to the synthesis of soluble protein and the release of extracellular polymeric substances. Alkaline phosphatase activity was generally enhanced in response to DIP deficiency. Both DIP and DOP promoted carbon uptake to the same extent. DOP groups absorbed carbon to synthesize energy and proteins in response to stress, while DIP groups were mainly used carbon for growth. They all reduced the content of microcystin releasing into the aquatic environment and therefore reduced ecological risk caused by microcystin. Compared with DIP, the expressions of photosynthesis-related genes were significantly down-regulated in DOP group, while the expressions of nucleoside phosphate catabolism, P transporter, and amino acid biosynthesis and metabolism were significantly up-regulated in response to P deficiency environment and the stress of 1.0 mg/L DOP concentration. In summary, the bioavailability of different P forms on cyanobacteria is different, so it is not sufficient to only use total P for assessing environmental risk. P forms should also be considered for risk management of freshwater ecosystems.


Asunto(s)
Microcystis , Fósforo , Microcystis/metabolismo , Microcystis/efectos de los fármacos , Fósforo/metabolismo , Contaminantes Químicos del Agua , Eutrofización
6.
Gene ; 930: 148853, 2024 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-39147111

RESUMEN

Leber's hereditary optic neuropathy (LHON) is a maternal inherited disorder, primarily due to mitochondrial DNA (mtDNA) mutations. This investigation aimed to assess the pathogenicity of m.3635G>A alteration known to confer susceptibility to LHON. The disruption of electrostatic interactions among S110 of the MT-ND1 and the side chain of E4, along with the carbonyl backbone of M1 in the NDUFA1, was observed in complex I of cybrids with m.3635G>A. This disturbance affected the complex I assembly activity by changing the mitochondrial respiratory chain composition and function. In addition, the affected cybrids exhibited notable deficiencies in complex I activities, including impaired mitochondrial respiration and depolarization of its membrane potential. Apoptosis was also stimulated in the mutant group, as witnessed by the secretion of cytochrome c and activation of PARP, caspase 3, 7, and 9 compared to the control. Furthermore, the mutant group exhibited decreased levels of autophagy protein light chain 3, accumulation of autophagic substrate P62, and impaired PINK1/Parkin-dependent mitophagy. Overall, the current study has confirmed the crucial involvement of the alteration of the m.3635G>A gene in the development of LHON. These findings contribute to a deeper comprehension of the pathophysiological mechanisms underlying LHON, providing a fundamental basis for further research.


Asunto(s)
Apoptosis , Mitocondrias , Mitofagia , NADH Deshidrogenasa , Atrofia Óptica Hereditaria de Leber , Atrofia Óptica Hereditaria de Leber/genética , Atrofia Óptica Hereditaria de Leber/metabolismo , Atrofia Óptica Hereditaria de Leber/patología , Humanos , Mitofagia/genética , Apoptosis/genética , Mitocondrias/metabolismo , Mitocondrias/genética , Mitocondrias/patología , NADH Deshidrogenasa/genética , NADH Deshidrogenasa/metabolismo , Mutación , ADN Mitocondrial/genética , Potencial de la Membrana Mitocondrial/genética , Proteínas Quinasas
7.
Ecotoxicol Environ Saf ; 283: 116860, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39126815

RESUMEN

INTRODUCTION: While ambient formaldehyde (HCHO) concentrations are increasing worldwide, there was limited research on its health effects. OBJECTIVES: To assess the association of long-term exposure to ambient HCHO with the risk of respiratory (RESP) mortality and the associated mortality burden in China. METHODS: Annual and seasonal RESP death and tropospheric HCHO vertical columns data were collected in 466 counties/districts across China during 2013-2016. A difference-in-differences approach combined with a generalized linear mixed-effects regression model was employed to assess the exposure-response association between long-term ambient HCHO exposure and RESP mortality risk. Additionally, we computed the attributable fraction (AF) to gauge the proportion of RESP mortality attributable to HCHO exposure. RESULTS: This analysis encompassed 560,929 RESP deaths. The annual mean ambient HCHO concentration across selected counties/districts was 8.02×1015 ± 2.22×1015 molec.cm-2 during 2013-2016. Each 1.00×1015 molec.cm-2 increase in ambient HCHO was associated with a 1.61 % increase [excess risk (ER), 95 % confidence interval (CI): 1.20 %, 2.03 %] in the RESP mortality risk. The AF of RESP mortality attributable to HCHO was 12.16 % (95 %CI:9.33 %, 14.88 %), resulting in an annual average of 125,422 (95 %CI:96,404, 153,410) attributable deaths in China. Stratified analyses suggested stronger associations in individuals aged ≥65 years old (ER=1.87 %, 95 %CI:1.43 %, 2.32 %), in cold seasons (ER=1.00 %, 95 %CI:0.56 %, 1.44 %), in urban areas (ER=1.65 %, 95 %CI:1.15 %, 2.16 %), and in chronic obstructive pulmonary disease patients (ER=1.95 %, 95 %CI:1.42 %, 2.48 %). CONCLUSIONS: This study suggested that long-term HCHO exposure may significantly increase the risk of RESP mortality, leading to a substantial mortality burden. Targeted measures should be implemented to control ambient HCHO pollution promptly.


Asunto(s)
Contaminantes Atmosféricos , Exposición a Riesgos Ambientales , Formaldehído , Formaldehído/análisis , Formaldehído/toxicidad , Formaldehído/efectos adversos , China/epidemiología , Humanos , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Enfermedades Respiratorias/mortalidad , Enfermedades Respiratorias/inducido químicamente , Estaciones del Año , Contaminación del Aire/efectos adversos , Contaminación del Aire/estadística & datos numéricos , Anciano , Medición de Riesgo , Masculino
8.
J Biol Chem ; 300(9): 107728, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39214298

RESUMEN

Leber's Hereditary Optic Neuropathy (LHON) is a rare, maternally inherited eye disease, predominantly due to the degeneration of retinal ganglion cells (RGCs). It is associated with a mitochondrial DNA (mtDNA) point mutation. Our previous study identified that the m.15927G > A homoplasmic mutation damaged the highly conserved base pairing (28C-42G) in anticodon stem of tRNAThr, caused deficient t6A modification and significantly decreased efficiency in aminoacylation and steady-state levels of tRNAThr, and led to mitochondrial dysfunction. Meanwhile, mechanisms underlying mtDNA mutations regulate intracellular signaling related to mitochondrial and cellular integrity are less explored. Here, we manifested that defective nucleotide modification induced by the m.15927G > A mutation interfered with the expression of nuclear genes involved in cytoplasmic proteins essential for oxidative phosphorylation system (OXPHOS), thereby impacting the assemble and integrity of OXPHOS complexes. As a result of these mitochondrial dysfunctions, there was an imbalance in mitochondrial dynamics, particularly distinguished by an increased occurrence of mitochondrial fission. Excessive fission compromised the autophagy process, including the initiation phase, formation, and maturation of autophagosomes. Both Parkin-mediated mitophagy and receptor-dependent mitophagy were significantly impaired in cybrids haboring the m.15927G > A mutation. These changes facilitated intrinsic apoptosis, as indicated by increased cytochrome c release and elevated levels of apoptosis-associated proteins (e.g., BAK, BAX, cleaved caspase 9, cleaved caspase 3, and cleaved PARP) in the mutant cybrids. This study demonstrates that the m.15927G > A mutation contributes to LHON by dysregulating OXPHOS biogenesis, aberrant quality control, increased autophagy, inhibited mitophagy, and abnormal apoptosis.

9.
Front Pharmacol ; 15: 1447677, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39130633

RESUMEN

Edible fungus polysaccharides have garnered significant attention from scholars due to their safety and potential anti-inflammatory activity. However, comprehensive summaries of their anti-inflammatory properties are still rare. This paper provides a detailed overview of the anti-inflammatory effects and mechanisms of these polysaccharides, as well as their impact on inflammation-related diseases. Additionally, the relationship between their structure and anti-inflammatory activity is discussed. It is believed that this review will greatly enhance the understanding of the application of edible fungus polysaccharides in anti-inflammatory treatments, thereby significantly promoting the development and utilization of edible fungi.

10.
BMC Cancer ; 24(1): 1033, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39169309

RESUMEN

OBJECTIVE: Transfer RNA-derived fragments (tRFs) are short non-coding RNA (ncRNA) sequences, ranging from 14 to 30 nucleotides, produced through the precise cleavage of precursor and mature tRNAs. While tRFs have been implicated in various diseases, including cancer, their role in lung adenocarcinoma (LUAD) remains underexplored. This study aims to investigate the impact of tRF-Val-CAC-010, a specific tRF molecule, on the phenotype of LUAD cells and its role in tumorigenesis and progression in vivo. METHODS: The expression level of tRF-Val-CAC-010 was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Specific inhibitors and mimics of tRF-Val-CAC-010 were synthesized for transient transfection. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8), while cell invasion and migration were evaluated through Transwell invasion and scratch assays. Flow cytometry was utilized to analyze cell cycle and apoptosis. The in vivo effects of tRF-Val-CAC-010 on tumor growth and metastasis were determined through tumor formation and metastasis imaging experiments in nude mice. RESULTS: The expression level of tRF-Val-CAC-010 was upregulated in A549 and PC9 LUAD cells (P < 0.01). Suppression of tRF-Val-CAC-010 expression resulted in decreased proliferation of A549 and PC9 cells (P < 0.001), reduced invasion and migration of A549 (P < 0.05, P < 0.001) and PC9 cells (P < 0.05, P < 0.01), enhanced apoptosis in both A549 (P < 0.05) and PC9 cells (P < 0.05), and increased G2 phase cell cycle arrest in A549 cells (P < 0.05). In vivo, the tumor formation volume in the tRF-inhibitor group was significantly smaller than that in the model and tRF-NC groups (P < 0.05). The metastatic tumor flux value in the tRF-inhibitor group was also significantly lower than that in the model and tRF-NC groups (P < 0.05). CONCLUSION: This study demonstrates that tRF-Val-CAC-010 promotes proliferation, migration, and invasion of LUAD cells and induces apoptosis in vitro, however, its specific effects on the cell cycle require further elucidation. Additionally, tRF-Val-CAC-010 enhances tumor formation and metastasis in vivo. Therefore, tRF-Val-CAC-010 may serve as a novel diagnostic biomarker and potential therapeutic target for LUAD.


Asunto(s)
Adenocarcinoma del Pulmón , Apoptosis , Movimiento Celular , Proliferación Celular , Neoplasias Pulmonares , Ratones Desnudos , Humanos , Animales , Ratones , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Células A549 , Carcinogénesis/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Metástasis de la Neoplasia
11.
Front Pediatr ; 12: 1419495, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39205667

RESUMEN

Background: Neonatal deaths often result from preventable conditions that can be addressed with appropriate interventions. This study aims to analyze the distribution of the causes of neonatal death and explore genetic variations that lead to congenital anomalies in Northwest China. Methods: This multi-center observational study was conducted across six medical centers in Shaanxi province, Northwest China. Clinical data were retrospectively collected from neonates admitted between 2016 and 2020. Kaplan-Meier analysis was utilized to estimate survival rates, while high-throughput sequencing platforms were employed to detect mutations causing congenital anomalies. Results: Among 73,967 neonates requiring hospital care, 424 neonatal deaths were recorded, leading to a neonatal mortality rate of 0.57%. The primary causes of death included neonatal respiratory distress syndrome (23.8%), birth asphyxia (19.8%), neonatal septicemia (19.3%), and congenital anomalies (13.6%). The leading causes of neonatal deaths due to congenital anomalies were congenital heart defects (38.6%), bronchopulmonary dysplasia (14.0%), and inherited metabolic disorders (10.5%). Genetic analysis identified 83 pathogenic or likely pathogenic variants in 23 genes among the neonates with congenital anomalies, including four novel mutations (c.4198+1G>T, c.1075delG, c.610-1G>A, c.7769C>T) in the ABCC8, CDKL5, PLA2G6, and NIPBL genes. Conclusion: Congenital anomalies represent a significant and preventable cause of neonatal deaths in Northwest China. Early detection of congenital anomalies through genetic testing and comprehensive prenatal care are crucial for reducing neonatal mortality rates and improving pregnancy outcomes.

12.
World J Clin Cases ; 12(19): 3807-3814, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38994320

RESUMEN

BACKGROUND: Patients in neurology intensive care units (ICU) are prone to pressure injuries (PU) due to factors such as severe illness, long-term bed rest, and physiological dysfunction. PU not only causes pain and complications to patients, but also increases medical burden, prolongs hospitalization time, and affects the recovery process. AIM: To evaluate and optimize the effectiveness of pressure injury prevention nursing measures in neurology ICU patients. METHODS: A retrospective study was conducted, and 60 patients who were admitted to the ICU of the Department of Neurology were selected and divided into an observation group and a control group according to the order of admission, with 30 people in each group. The observation group implemented pressure injury prevention and nursing measures, while the control group adopted routine care. RESULTS: Comparison between observation and control groups following pressure injury prevention nursing intervention revealed significantly lower incidence rates in the observation group compared to the control group at 48 h (8.3% vs 26.7%), 7 d (16.7% vs 43.3%), and 14 d (20.0% vs 50.0%). This suggests a substantial reduction in pressure injury incidence in the observation group, with the gap widening over time. Additionally, patients in the observation group exhibited quicker recovery, with a shorter average time to get out of bed (48 h vs 72 h) and a shorter average length of stay (12 d vs 15 d) compared to the control group. Furthermore, post-intervention, patients in the observation group reported significantly improved quality of life scores, including higher scores in body satisfaction, feeling and function, and comfort (both psychological and physiological), indicating enhanced overall well-being and comfort following the implementation of pressure injury prevention nursing measures. CONCLUSION: Implementing pressure injury preventive care measures for neurology ICU patients will have better results.

13.
J Mol Neurosci ; 74(3): 73, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39046556

RESUMEN

Low back pain (LBP) has become a leading cause of disability worldwide. Astrocyte activation in the spinal cord plays an important role in the maintenance of latent sensitization of dorsal horn neurons in LBP. However, the role of spinal c-Jun N-terminal kinase (JNK) in astrocytes in modulating pain behavior of LBP model rats and its neurobiological mechanism have not been elucidated. Here, we investigate the role of the JNK signaling pathway on hypersensitivity and anxiety-like behavior caused by repetitive nerve growth factor (NGF) injections in male non-specific LBP model rats. LBP was produced by two injections (day 0, day 5) of NGF into multifidus muscle of the low backs of rats. We observed prolonged mechanical and thermal hypersensitivity in the low backs or hindpaws. Persistent anxiety-like behavior was observed, together with astrocyte, p-JNK, and neuronal activation and upregulated expression of monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-X-C motif) ligand 1 (CXCL1) proteins in the spinal L2 segment. Second, the JNK inhibitor SP600125 was intrathecally administrated in rats from day 10 to day 12. It attenuated mechanical and thermal hypersensitivity of the low back or hindpaws and anxiety-like behavior. Meanwhile, SP600125 decreased astrocyte and neuronal activation and the expression of MCP-1 and CXCL1 proteins. These results showed that hypersensitivity and anxiety-like behavior induced by NGF in LBP rats could be attenuated by the JNK inhibitor, together with downregulation of spinal astrocyte activation, neuron activation, and inflammatory cytokines. Our results indicate that intervening with the spinal JNK signaling pathway presents an effective therapeutic approach to alleviating LBP.


Asunto(s)
Ansiedad , Dolor de la Región Lumbar , Sistema de Señalización de MAP Quinasas , Ratas Sprague-Dawley , Animales , Masculino , Ratas , Ansiedad/etiología , Dolor de la Región Lumbar/metabolismo , Dolor de la Región Lumbar/etiología , Antracenos/farmacología , Antracenos/uso terapéutico , Hiperalgesia/metabolismo , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Factor de Crecimiento Nervioso/metabolismo , Médula Espinal/metabolismo , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo
14.
Aquat Toxicol ; 272: 106967, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38833998

RESUMEN

Microplastics (MPs) are ubiquitous in aquatic environments, which can act as carriers to affect the bioavailability of heavy metals. The aging process in the environment changes the physicochemical properties of MPs, thereby affecting their environmental behavior and co-toxicity with other pollutants. However, relevant research is limited. In this study, we compared the properties and Cu2+ adsorption capacity of pristine and aged polytetrafluoroethylene (PTFE) MPs and further explored the influence on copper bioavailability and bio-effects on Microcystis aeruginosa. Aging process induced surface oxidation and cracks of PTFE MPs, and decreased the stability of MPs in water by increasing zeta potential. PTFE MPs had a strong adsorption capacity for Cu2+ and increased the bioavailability of copper to microalgae, which was not affected by the aging process. Pristine and aged PTFE MPs adhered to cyanobacterium surfaces and caused shrinkage and deformation of cells. Inhibition of cyanobacterium growth, photosynthesis and reduction of total antioxidant capacity were observed in the treatment of PTFE MPs. Combined exposure of pristine MPs and Cu2+ had stronger toxic effects to cyanobacterium, and increased Microcystin-LR release, which could cause harm to aquatic environment. Aging reduced the toxic effects of PTFE MPs on microalgae. Furthermore, soluble exopolysaccharide (EPS) content was significantly higher in co-exposure of aged MPs and Cu2+, which could reduce the toxicity to cyanobacterium cells. These results indicate that aging process alleviates the toxicity to microalgae and environmental risks caused by PTFE MPs. This study improves understanding of the combined toxicity of aged MPs and metals in freshwater ecosystems.


Asunto(s)
Disponibilidad Biológica , Cobre , Microcystis , Microplásticos , Politetrafluoroetileno , Contaminantes Químicos del Agua , Microcystis/efectos de los fármacos , Cobre/toxicidad , Contaminantes Químicos del Agua/toxicidad , Microplásticos/toxicidad , Politetrafluoroetileno/química , Politetrafluoroetileno/toxicidad , Rayos Ultravioleta , Adsorción , Microalgas/efectos de los fármacos
15.
J Cell Mol Med ; 28(11): e18466, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38847482

RESUMEN

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by pulmonary and systemic congestion resulting from left ventricular diastolic dysfunction and increased filling pressure. Currently, however, there is no evidence on effective pharmacotherapy for HFpEF. In this study, we aimed to investigate the therapeutic effect of total xanthones extracted from Gentianella acuta (TXG) on HFpEF by establishing an high-fat diet (HFD) + L-NAME-induced mouse model. Echocardiography was employed to assess the impact of TXG on the cardiac function in HFpEF mice. Haematoxylin and eosin staining, wheat germ agglutinin staining, and Masson's trichrome staining were utilized to observe the histopathological changes following TXG treatment. The results demonstrated that TXG alleviated HFpEF by reducing the expressions of genes associated with myocardial hypertrophy, fibrosis and apoptosis. Furthermore, TXG improved cardiomyocyte apoptosis by inhibiting the expression of apoptosis-related proteins. Mechanistic investigations revealed that TXG could activate the inositol-requiring enzyme 1α (IRE1α)/X-box-binding protein 1 (Xbp1s) signalling pathway, but the knockdown of IRE1α using the IRE1α inhibitor STF083010 or siRNA-IRE1α impaired the ability of TXG to ameliorate cardiac remodelling in HFpEF models. In conclusion, TXG alleviates myocardial hypertrophy, fibrosis and apoptosis through the activation of the IRE1α/Xbp1s signalling pathway, suggesting its potential beneficial effects on HFpEF patients.


Asunto(s)
Apoptosis , Endorribonucleasas , Insuficiencia Cardíaca , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Proteína 1 de Unión a la X-Box , Xantonas , Animales , Endorribonucleasas/metabolismo , Endorribonucleasas/genética , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Proteína 1 de Unión a la X-Box/metabolismo , Proteína 1 de Unión a la X-Box/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Transducción de Señal/efectos de los fármacos , Ratones , Masculino , Xantonas/farmacología , Xantonas/aislamiento & purificación , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Dieta Alta en Grasa/efectos adversos , Fibrosis , Volumen Sistólico/efectos de los fármacos
16.
Front Oncol ; 14: 1395144, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38919535

RESUMEN

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL), also known as MALT lymphoma, is an extranodal multiorgan-invasive proliferative lymphoma composed of small B cells with variable morphology. It most commonly occurs in the digestive tract, with a high prevalence in the stomach, but EMZL originating in the small intestine is rare and lacks specificity in clinical manifestations, which makes it easy to be misdiagnosed. Herein, we report a rare case of small intestinal EMZL presentation as intussusception in a 32-year-old man. A colonoscopy performed at the local hospital revealed a pedicled polyp about 5 cm × 5 cm in size with a rough surface, and hyperemia was seen in the ileocecal region. He was admitted to our hospital for a polypectomy. A contrast-enhanced computed tomographic (CT) scan suggested ileocolic intussusception, which was subsequently confirmed by a colonoscopy in our hospital. Adult intussusception is relatively rare, with 90% of cases having a known causative mechanism and 40% of cases caused by primary or secondary malignancies. Therefore, we performed a laparoscopic-assisted right hemicolectomy for the patient. The resected specimen showed that the terminal ileum was intussuscepted into the ascending colon, and the intussusception was hyperemia and edema. A 2.5 cm × 2.5 cm × 1.5 cm mass was seen at the end of the intussusception. Postoperative pathology revealed that the mass was EMZL, partially transformed into a large B-cell lymphoma. The patient was transferred to the hematology department and completed a PET-CT showing postoperative manifestations of primary intestinal lymphoma, Lugano staging IE2. Although EMZL was an indolent lymphoma and the patient was in the early stages, the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen was given in view of the histological transformation. The patient is in regular follow-up. This was a rare case of small intestinal mass due to EMZL presented as intussusception in adults, which highlighted laparoscopic-assisted enterectomy as a potential therapeutic approach in the multidisciplinary collaborative therapy of small intestine EMZL.

17.
Clin Microbiol Infect ; 30(9): 1183-1189, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38852851

RESUMEN

OBJECTIVES: With remarkable progress in the field of respiratory syncytial virus (RSV) prophylaxis, it is critical to understand population immunity against RSV. We aim to describe the RSV pre-F IgG antibodies across all age groups in Southern China and to evaluate the risk factors associated with lower antibody levels. METHODS: We performed a community-based cross-sectional sero-epidemiological study in Anhua County, Hunan Province, Southern China, from July 15, 2021, to November 5, 2021. Serum samples were tested for IgG antibodies against the RSV prefusion F (pre-F) protein using an enzyme-linked immunosorbent assay. We estimated the geometric mean titres (GMTs) and seropositivity rates across all age groups. The generalized linear models were built to identify factors associated with antibody levels. RESULTS: A total of 890 participants aged 4 months to older than 89 years were enrolled. The lowest RSV pre-F IgG GMTs were observed in infants and toddlers aged 4 months to younger than 2 years (3.0; 95% CI, 2.6-3.5). With increasing age, the RSV pre-F IgG GMT increased to 4.3 (95% CI, 4.1-4.4) between the ages of 2 and younger than 5 years and then stabilized at high levels throughout life. All the children had serological evidence of RSV infection by the age of 5 years. Age was associated with RSV pre-F antibody levels in children, with an estimated 1.9-fold (95% CI, 0.8-3.6) increase in titre per year before 5 years of age, although it was not significantly associated with antibody levels in adults aged older than 60 years. DISCUSSION: Our findings could provide a comprehensive understanding of the gaps in RSV immunity at the population level and inform the prioritization of immunization platforms.


Asunto(s)
Anticuerpos Antivirales , Inmunoglobulina G , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Humanos , China/epidemiología , Estudios Transversales , Lactante , Anticuerpos Antivirales/sangre , Infecciones por Virus Sincitial Respiratorio/inmunología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Preescolar , Adulto , Persona de Mediana Edad , Femenino , Virus Sincitial Respiratorio Humano/inmunología , Masculino , Inmunoglobulina G/sangre , Niño , Adulto Joven , Anciano , Adolescente , Estudios Seroepidemiológicos , Anciano de 80 o más Años , Ensayo de Inmunoadsorción Enzimática , Formación de Anticuerpos , Factores de Riesgo
19.
Surg Endosc ; 38(8): 4512-4520, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38914885

RESUMEN

BACKGROUND: Endoscopic balloon dilation (EBD) is a safe and effective treatment for Crohn's disease (CD)-associated strictures. However, serial EBDs have rarely been reported. This study aimed to evaluate the efficacy and safety of serial EBDs for treating CD-associated duodenal strictures compared with intermittent EBDs. METHODS: Patients with CD-associated duodenal strictures who underwent EBD were recruited. The clinical data, stricture characteristics, number of EBDs, dilation diameter, complications, surgical interventions, and follow-up periods were recorded. Patients were divided into a serial dilation group and an intermittent dilation group to analyze the differences in safety and efficacy. RESULTS: Forty-five patients with duodenal CD-associated strictures underwent a total of 139 dilations. A total of 23 patients in the serial dilation group underwent 72 dilations, for a median of 3 (range 3 ~ 4) dilations per patient, and 22 patients in the intermittent dilation group underwent 67 dilations, for a median of 3 (range 1 ~ 6) dilations per patient. Technical success was achieved in 97.84% (136/139) of the patients. During the follow-up period, three patients in the intermittent dilation group underwent surgery, and the total clinical efficacy was 93.33% (42/45). No difference in safety or short-term efficacy was noted between the two groups, but serial EBDs exhibited significantly greater clinical efficacy between 6 months and 2 years. No significant difference in recurrence-free survival was observed, but the median longest recurrence-free survival and recurrence-free survival after the last EBD in the serial dilation group were 693 days (range 298 ~ 1381) and 815 days (range 502 ~ 1235), respectively, which were significantly longer than the 415 days (range 35 ~ 1493) and 291 days (range 34 ~ 1493) in the intermittent dilation group (p = 0.013 and p = 0.000, respectively). At the last follow-up, the mean diameter of the duodenal lumen was 1.17 ± 0.07 cm in the serial dilation group, which was greater than the 1.11 ± 0.10 cm in the intermittent dilation group (p = 0.018). We also found that the Simple Endoscopic Score for Crohn's Disease was associated with an increased risk of surgical intervention (HR 2.377, 95% CI 1.125-5.020; p = 0.023) and recurrence at 6 months after the last EBD (HR 0.698, 95% CI 0.511-0.953; p = 0.024), as assessed by univariate analysis. CONCLUSIONS: Compared to the intermittent EBDs, serial EBDs for duodenal CD-associated strictures exhibit greater clinical efficacy within two years and could delay stricture recurrence. We suggest that serial EBDs can be a novel option for endoscopic treatment of duodenal CD-associated strictures.


Asunto(s)
Enfermedad de Crohn , Dilatación , Humanos , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/terapia , Femenino , Masculino , Adulto , Dilatación/métodos , Dilatación/instrumentación , Persona de Mediana Edad , Resultado del Tratamiento , Constricción Patológica/etiología , Constricción Patológica/cirugía , Adulto Joven , Estudios Retrospectivos , Obstrucción Duodenal/etiología , Obstrucción Duodenal/terapia , Obstrucción Duodenal/cirugía , Adolescente , Enfermedades Duodenales/terapia , Enfermedades Duodenales/etiología , Enfermedades Duodenales/cirugía
20.
Influenza Other Respir Viruses ; 18(5): e13301, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38733199

RESUMEN

BACKGROUND: Human contact patterns are a key determinant driving the spread of respiratory infectious diseases. However, the relationship between contact patterns and seasonality as well as their possible association with the seasonality of respiratory diseases is yet to be clarified. METHODS: We investigated the association between temperature and human contact patterns using data collected through a cross-sectional diary-based contact survey in Shanghai, China, between December 24, 2017, and May 30, 2018. We then developed a compartmental model of influenza transmission informed by the derived seasonal trends in the number of contacts and validated it against A(H1N1)pdm09 influenza data collected in Shanghai during the same period. RESULTS: We identified a significant inverse relationship between the number of contacts and the seasonal temperature trend defined as a spline interpolation of temperature data (p = 0.003). We estimated an average of 16.4 (95% PrI: 15.1-17.5) contacts per day in December 2017 that increased to an average of 17.6 contacts (95% PrI: 16.5-19.3) in January 2018 and then declined to an average of 10.3 (95% PrI: 9.4-10.8) in May 2018. Estimates of influenza incidence obtained by the compartmental model comply with the observed epidemiological data. The reproduction number was estimated to increase from 1.24 (95% CI: 1.21-1.27) in December to a peak of 1.34 (95% CI: 1.31-1.37) in January. The estimated median infection attack rate at the end of the season was 27.4% (95% CI: 23.7-30.5%). CONCLUSIONS: Our findings support a relationship between temperature and contact patterns, which can contribute to deepen the understanding of the relationship between social interactions and the epidemiology of respiratory infectious diseases.


Asunto(s)
Gripe Humana , Estaciones del Año , Humanos , Gripe Humana/transmisión , Gripe Humana/epidemiología , China/epidemiología , Estudios Transversales , Infecciones del Sistema Respiratorio/transmisión , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Temperatura , Femenino , Masculino , Adulto , Subtipo H1N1 del Virus de la Influenza A , Persona de Mediana Edad , Adulto Joven , Adolescente , Incidencia , Niño
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