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1.
Pediatr Infect Dis J ; 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39348504

RESUMEN

BACKGROUND: Peginterferon (PegIFN) has shown promising results in the treatment of chronic hepatitis B (CHB). This study aimed to evaluate the effects of PegIFN α-2b on growth and thyroid function in young children with CHB. METHODS: A retrospective study was performed by extracting clinical data from children with CHB who received PegIFN α-2b monotherapy at the Public Health Clinical Center of Chengdu between June 2017 and December 2020. Mean, SD, independent samples t test and 1-way repeated analysis of variance were used to evaluate relevant data. RESULTS: A total of 62 children were included in this study. Overall, significant differences were observed in the weight-for-age z score (WAZ), height-for-age z score (HAZ) and body mass index-for-age z score (BAZ) at different time points ( P < 0.001). WAZ, HAZ and BAZ were not affected by PegIFN α-2b at 24 weeks of treatment (all P > 0.05). WAZ, HAZ and BAZ at the end of treatment and 48 weeks after treatment; WAZ at 96 weeks after treatment were lower than baseline levels (all P < 0.05). No statistical differences were found in HAZ and BAZ at 96 weeks after treatment compared with baseline. Thyroid dysfunction developed in 17.7% of children during the treatment. Thyroid dysfunction was transient and had no effect on growth. CONCLUSIONS: PegIFN α-2b has inhibitory effects on growth and can increase the incidence of thyroid dysfunction in young children with CHB. These effects are generally reversible with the cessation of therapy, although WAZ had not returned to baseline after 96 weeks of observation.

2.
Phytomedicine ; 134: 155976, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39265445

RESUMEN

BACKGROUND: Pulmonary hypertension (PH) is a chronic lung disease characterized by the progressive pulmonary vascular remodeling with increased pulmonary arterial pressure and right ventricular failure. Pulmonary vascular remodeling involves the proliferation, migration, and resistance to apoptosis of pulmonary artery smooth cells (PASMCs). Parthenolide (PTN) is a bioactive compound derived from a traditional medical plant feverfew (Tanacetum parthenium), and it has been studied for treatment of pulmonary fibrosis, lung cancer, and other related ailments. However, the function of PTN in the treatment of PH has not been studied. PURPOSE: This study aimed to evaluate the anti-proliferation and pro-apoptosis effects of PTN on PH and investigate its potential mechanisms. METHODS: An in vivo hypoxia-induced pulmonary hypertension (HPH) model was established by maintaining male rats in a hypoxia chamber (10% O2) for 3 weeks, and PTN was intraperitoneally administered at the dose of 10 or 30 mg/kg. We assessed the impact of PTN on mean pulmonary arterial pressure (mPAP), pulmonary vascular remodeling, and right ventricular hypertrophy. In vitro, we evaluated hypoxia-induced cellular proliferation, migration, and apoptosis of rat PASMCs. Proteins related to the STAT3 signaling axis were analyzed by western blotting and immunofluorescence assays. Recovery experiments were performed using the STAT3 activator, colivelin TFA. RESULTS: PTN significantly alleviated the symptoms of HPH rats by attenuating pulmonary arterial remodeling. It also prevented the proliferation and migration of PASMCs. PTN also induced the apoptosis of PASMCs. PTN could directly interact with STAT3 and markedly inhibited STAT3 phosphorylation and nuclear translocation. In vitro, and in vivo experiments demonstrated that overexpression of STAT3 partially suppressed the effect of PTN. CONCLUSION: Our study indicated that PTN alleviated hypoxia-induced pulmonary hypertension in rats by suppressing STAT3 activity.


Asunto(s)
Apoptosis , Proliferación Celular , Hipertensión Pulmonar , Hipoxia , Arteria Pulmonar , Ratas Sprague-Dawley , Factor de Transcripción STAT3 , Sesquiterpenos , Transducción de Señal , Remodelación Vascular , Animales , Factor de Transcripción STAT3/metabolismo , Sesquiterpenos/farmacología , Hipertensión Pulmonar/tratamiento farmacológico , Masculino , Transducción de Señal/efectos de los fármacos , Hipoxia/tratamiento farmacológico , Hipoxia/complicaciones , Arteria Pulmonar/efectos de los fármacos , Remodelación Vascular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ratas , Movimiento Celular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Tanacetum parthenium/química , Modelos Animales de Enfermedad , Hipertrofia Ventricular Derecha/tratamiento farmacológico
3.
Nutr J ; 23(1): 104, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39252042

RESUMEN

BACKGROUND: The fat-to-muscle mass ratio (FMR), integrating the antagonistic effects of fat and muscle mass, has been suggested as a valuable indicator to assess cardiometabolic health independent of overall adiposity. However, the specific associations of total and regional FMR with cardiometabolic risk are poorly understood. We aimed to examine sex-specific associations of total and regional FMR with single and clustered cardiometabolic risk factors (CRFs). METHODS: 13,505 participants aged 20 years and above were included in the cross-sectional study. Fat mass and muscle mass were assessed using a bioelectrical impedance analysis device. FMR was estimated as fat mass divided by muscle mass in corresponding body parts (whole body, arm, leg, and trunk). Clustered CRFs was defined as the presence of two or more risk factors, including hypertension, elevated blood glucose, dyslipidemia, insulin resistance (IR), and hyperuricemia. IR was assessed by the triglyceride glucose (TyG) index. Multivariable logistic regression models were applied to explore the associations of FMR in the whole body and body parts with single and clustered CRFs. RESULTS: The odds ratios (ORs) increased significantly for all single and clustered CRFs with the per quartile increase of total and regional FMR in both sexes (P for trend < 0.001), following adjustment for confounders. Among the regional parts, FMRs of the legs presented the strongest associations for clustered CRFs in both men and women, with adjusted OR of 8.54 (95% confidence interval (CI): 7.12-10.24) and 4.92 (95% CI: 4.24-5.71), respectively. Significant interactions (P for interaction < 0.05) were identified between age and FMRs across different body parts, as well as between BMI status and FMRs in different regions for clustered CRFs. Restricted cubic splines revealed significant non-linear relationships between FMRs of different body parts and clustered CRFs in both sexes (P for nonlinear < 0.05). CONCLUSIONS: FMRs in the whole body and different regions were significantly associated with single and clustered CRFs in the general Chinese population. The association between FMR and clustered CRFs was more pronounced in youngers than in the elderly.


Asunto(s)
Factores de Riesgo Cardiometabólico , Encuestas Epidemiológicas , Humanos , Masculino , Femenino , China/epidemiología , Estudios Transversales , Adulto , Persona de Mediana Edad , Encuestas Epidemiológicas/estadística & datos numéricos , Encuestas Epidemiológicas/métodos , Factores Sexuales , Tejido Adiposo , Músculo Esquelético , Adiposidad , Composición Corporal , Adulto Joven , Factores de Riesgo , Anciano , Resistencia a la Insulina , Enfermedades Cardiovasculares/epidemiología
4.
Sci Total Environ ; 951: 175430, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39128524

RESUMEN

Biomass burning is a primary source of atmospheric nitrogen oxide (NOx), however, the lack of isotopic fingerprints from biomass burning limits their use in tracing atmospheric nitrate (NO3-) and NOx. A total of 25 biomass fuels from 10 provinces and regions in China were collected, and the δ15N values of biomass fuels (δ15N-biomass) and δ15N-NOx values of biomass burning (δ15N-NOx values of BB, open burning, and rural cooking stove burning) were determined. The δ15N-NOx values of open burning and rural cooking stove burning ranged from -0.8 ‰ to 11.6 ‰ and 0.8 ‰ to 9.5 ‰, respectively, indicating a significant linear relation with δ15N-biomass. Based on the measured δ15N-NOx values of BB and biomass burning emission inventory data, the δ15N-NOx values of BB in different provinces and regions of China were calculated using the δ15N-NOx model, with a mean value of 5.0 ± 1.8 ‰. The spatial variations in the estimated δ15N-NOx values of BB in China were mainly controlled by the differences in the δ15N-NOx values and the proportions of NOx emissions from various straw burning activities in provinces and regions of China. Furthermore, by using the combined local emissions of biomass burning with regional transportations of NOx based on air-mass backward trajectories, we established an improved δ15N-NOx model and obtained more accurate δ15N-NOx values of BB in regions (2.3 ‰ to 8.4 ‰). By utilising the reported δ15N-NOx values of precipitation and particulate matter from 21 cities in China and the more accurate δ15N-NOx values of BB, the NOx contributions from four sources (mobile sources, coal combustion, biomass burning, and microbial N cycle) at the national scale were estimated using a Bayesian model. The significant contributions of biomass burning (20.9 % to 44.3 %) to NOx emissions were revealed, which is vital for controlling NOx emissions in China.

5.
Mol Cell Probes ; 77: 101981, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39197503

RESUMEN

The clinical treatment of hepatocellular carcinoma (HCC) is still a heavy burden worldwide. Intracellular microRNAs (miRNAs) commonly express abnormally in cancers, thus they are potential therapeutic targets for cancer treatment. miR-21 is upregulated in HCC whereas miR-122 is enriched in normal hepatocyte but downregulated in HCC. In our study, we first generated a reporter genetic switch compromising of miR-21 and miR-122 sponges as sensor, green fluorescent protein (GFP) as reporter gene and L7Ae:K-turn as regulatory element. The reporter expression was turned up in miR-21 enriched environment while turned down in miR-122 enriched environment, indicating that the reporter switch is able to respond distinctly to different miRNA environment. Furthermore, an AAT promoter, which is hepatocyte-specific, is applied to increase the specificity to hepatocyte. A killing switch with AAT promoter and an apoptosis-inducing element, Bax, in addition to miR-21 and miR-122 significantly inhibited cell viability in Huh-7 by 70 % and in HepG2 by 60 %. By contrast, cell viability was not affected in five non-HCC cells. Thus, we provide a novel feasible strategy to improve the safety of miRNA-based therapeutic agent to cancer.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Regiones Promotoras Genéticas , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Regiones Promotoras Genéticas/genética , Genes Reporteros , Células Hep G2 , Línea Celular Tumoral , Supervivencia Celular/genética , Regulación Neoplásica de la Expresión Génica , Proteínas Fluorescentes Verdes/metabolismo , Proteínas Fluorescentes Verdes/genética , Especificidad de Órganos/genética
6.
Eur J Appl Physiol ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164441

RESUMEN

PURPOSE: This study aimed to compare variations between the earlobe and fingertip sampling sites in exercises dominated by upper body muscle exertion. It also sought to investigate capillary blood lactate differences between Lactate Scout 4 (LS4) and a bench-top analyzer (Biosen S-Line analyzer, BSL) during Double Poling. METHODS: Blood samples were collected from the earlobe and fingertip immediately before exercise, at the end of each of five stages, and at 1-, 3-, 5-, and 7-min post-exercise. Forty healthy university students participated as volunteers. During the study, they performed double poling on a ski ergometer with progressively increasing load. Lactate levels were measured using both the BSL and LS4 analyzers. RESULTS: Fingertip Bla values were significantly higher than earlobe values, with a mean bias of -0.66 mmol/L, reaching -0.86 mmol/L in the 4-8 mmol/L range. At the earlobe, the highest CCC between BSL and LS4-a was 0.84 (> 8 mmol/L), and for BSL and LS4-b, it was 0.85 (> 8 mmol/L). At the fingertip, the highest CCC between BSL and LS4-c was 0.68 (> 8 mmol/L), and for BSL and LS4-d, it was 0.52 (> 8 mmol/L). Comparing LS4-a and LS4-b at the earlobe, the highest CCC was 0.83 (0-4 mmol/L). At the fingertip, comparing LS4-c and LS4-d, the highest CCC was 0.68 (> 8 mmol/L). CONCLUSIONS: Blood lactate concentrations are higher at the fingertip than the earlobe during SkiErg double poling. The LS4 is less reliable, especially at the fingertip, so using the earlobe with the BSL analyzer is recommended for accurate measurements.

7.
Diabetes Res Clin Pract ; 214: 111783, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39002932

RESUMEN

AIMS: The evidence for joint and independent associations of low muscle mass and low muscle strength with diabetes is limited and mixed. The study aimed to determine the associations of muscle parameters (muscle mass, strength, quality, and sarcopenia) and sarcopenia obesity with diabetes, and the previously unstudied mediating effect of inflammation. MATERIALS AND METHODS: A total of 13,420 adults from the 2023 China National Health Survey (CNHS) and 5,380 adults from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) were included in this study. Muscle mass was determined using bioelectrical impedance analysis (BIA) in the CNHS, and whole-body dual X-ray absorptiometry (DXA) in the NHANES. Muscle strength was assessed using digital hand dynamometer. Multivariate logistic regression models were used to evaluate the associations of muscle parameters and sarcopenia obesity with diabetes. Inflammatory status was assessed using blood cell counts and two systemic inflammation indices (platelet-to-lymphocyte ratio (PLR) and system inflammation response index (SIRI)). Mediation analysis was conducted to examine inflammation's role in these associations. RESULTS: Low muscle mass and strength were independently related to diabetes. Low muscle quality was associated with elevated diabetes risk. Sarcopenia has a stronger association with diabetes compared to low muscle strength alone or mass alone (CNHS, odds ratio (OR) = 1.93, 95 % confidence interval (CI):1.64-2.27; NHANES, OR = 3.80, 95 %CI:2.58-5.58). Participants with sarcopenia obesity exhibit a higher risk of diabetes than those with obesity or sarcopenia alone (CNHS, OR = 2.21, 95 %CI:1.72-2.84; NHANES, OR = 6.06, 95 %CI:3.64-10.08). Associations between muscle parameters and diabetes were partially mediated by inflammation (mediation proportion: 1.99 %-36.64 %, P < 0.05). CONCLUSION: Low muscle mass and muscle strength are independently or jointly associated with diabetes, and inflammation might be a potential mechanism underlying this association. Furthermore, the synergistic effects of sarcopenia and obesity could significantly increase diabetes risk.


Asunto(s)
Inflamación , Fuerza Muscular , Músculo Esquelético , Encuestas Nutricionales , Sarcopenia , Humanos , Masculino , Femenino , China/epidemiología , Inflamación/fisiopatología , Inflamación/epidemiología , Persona de Mediana Edad , Sarcopenia/epidemiología , Sarcopenia/fisiopatología , Sarcopenia/patología , Adulto , Fuerza Muscular/fisiología , Estados Unidos/epidemiología , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Diabetes Mellitus/epidemiología , Diabetes Mellitus/fisiopatología , Obesidad/epidemiología , Obesidad/fisiopatología , Obesidad/complicaciones , Anciano , Absorciometría de Fotón
8.
J Exerc Sci Fit ; 22(4): 350-358, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39027081

RESUMEN

Objective: The aims of this study were to examine the effect of SARS-CoV-2 infection on cardiorespiratory fitness (CRF) and time-trial performance in vaccinated well-trained young kayak athletes. Methods: This is a longitudinal observational study. Sixteen (7 male, 9 female) vaccinated kayakers underwent body composition assessment, maximal graded exercise test, and 1000-m time-trial tests 21.9 ± 1.7 days before and 66.0 ± 2.2 days after the SARS-CoV-2 infection. The perception of training load was quantified with Borg's CR-10 scale before and after the infection return to sport period. Results: There were significant decreases in peak oxygen uptake (-9.7 %; effect size [ES] = 1.38), peak oxygen pulse (-5.7 %; ES = 0.96), and peak heart rate (-1.9 %; ES = 0.61). Peak minute ventilation, and minute ventilation/carbon dioxide production slope were unchanged after infection compared to the pre-infection values. In the entire 1000-m, the impaired tendencies were found in completion time, mean power, and mean speed (-2.4 to 1.2 %; small ESs = -0.40 to 0.47) as well as significant changes in stroke rate and stroke length (-4.5 to 3.7 %; ESs = -0.60 to 0.73). Conclusion: SARS-CoV-2 infection decreased CRF and time-trial performance even two months after return to regular training in vaccinated athletes.

9.
Front Neurol ; 15: 1429698, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39081339

RESUMEN

Background: Multiple sclerosis (MS) and Cerebral Small Vessel Disease (CSVD) exhibit some similarities in Magnetic resonance imaging (MRI), potentially leading to misdiagnosis and delaying effective treatment windows. It is unclear whether CSVD can be detected with Paramagnetic Rim Lesions (PRL), which is special in MS. Objective: We aimed to investigate whether PRL can serve as a neuroimaging marker for discriminating between MS and CSVD. Methods: In this retrospective study, 49 MS and 104 CSVD patients underwent 3.0 T Magnetic resonance imaging (MRI). Visual assessment of 37 MS patients and 89 CSVD patients with or without lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces (EPVS), white matter hyperintensity (WMH), central vein sign (CVS), and PRL. The distribution and number of PRL were then counted. Results: Our study found that PRL was detected in over half of the MS patients but was entirely absent in CSVD patients (78.38 vs. 0%, p < 0.0001), and PRL showed high specificity with good sensitivity in discriminating between MS and CSVD (sensitivity: 78.38%, specificity: 100%, AUC: 0.96). Conclusion: Paramagnetic Rim Lesions is a special imaging feature in MS, absent in CSVD. Detection of PRL can be very helpful in the clinical management of MS and CSVD.

10.
J Immunol ; 213(4): 469-480, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38922186

RESUMEN

Neutrophils accumulate early in tissue injury. However, the cellular and functional heterogeneity of neutrophils during homeostasis and in response to tissue damage remains unclear. In this study, we use larval zebrafish to understand neutrophil responses to thermal injury. Single-cell transcriptional mapping of myeloid cells during a 3-d time course in burn and control larvae revealed distinct neutrophil subsets and their cell-cell interactions with macrophages across time and conditions. The trajectory formed by three zebrafish neutrophil subsets resembles human neutrophil maturation, with varying transition patterns between conditions. Through ligand-receptor cell-cell interaction analysis, we found that neutrophils communicate more in burns in a pathway and temporal manner. Finally, we identified the correlation between zebrafish myeloid signatures and human burn severity, establishing GPR84+ neutrophils as a potential marker of early innate immune response in burns. This work builds a comparative single-cell transcriptomic framework to identify neutrophil markers of tissue damage using model organisms.


Asunto(s)
Quemaduras , Larva , Neutrófilos , Análisis de la Célula Individual , Pez Cebra , Animales , Pez Cebra/inmunología , Neutrófilos/inmunología , Quemaduras/inmunología , Larva/inmunología , Larva/genética , Transcriptoma , Humanos , Inmunidad Innata , Modelos Animales de Enfermedad , Macrófagos/inmunología , Comunicación Celular/inmunología
11.
J Sports Sci Med ; 23(2): 418-424, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38841636

RESUMEN

To determine how lateral shuffling/lateral shuffle (LS) -induced fatigue affects ankle proprioception and countermovement jump (CMJ) performance. Eighteen male college athletes performed 6 modes of a repeated LS protocol with 2 distances (2.5 and 5 m) and 3 speeds (1.6, 1.8, and 2.0 m/s). After LS, ankle inversion proprioception (AIP) was measured using the active movement extent discrimination apparatus (AMEDA). CMJ, blood lactate (BLa), heart rate (HR) and rating of perceived exertion (RPE) were measured before and after LS. The number of changes of direction (CODs) in each protocol was recorded. LS-induced fatigue was evident in BLa, HR and RPE (all p < 0.05), increasing with shorter shuffle distance and faster speed. RM-ANOVA showed a significant distance main effect on both AIP (p < 0.01) and CMJ (p < 0.05), but the speed main effect was only significant for CMJ (p ≤ 0.001), not AIP (p = 0.87). CMJ performance was correlated with BLa, HR and RPE (r values range from -0.62 to -0.32, all p ≤ 0.001). AIP was only correlated with CODs (r = -0.251, p < 0.01). These results suggested that in LS, shorter distance, regardless of speed, was associated with worse AIP, whereas subsequent CMJ performance was affected by both LS distance and speed. Hence, AIP performance was not related to physiological fatigue, but CMJ performance was. Results imply that LS affects processing proprioceptive input and producing muscular output differently, and that these two aspects of neuromuscular control are affected by physiological fatigue to varying degrees. These findings have implications for injury prevention and performance enhancement.


Asunto(s)
Tobillo , Rendimiento Atlético , Frecuencia Cardíaca , Ácido Láctico , Fatiga Muscular , Propiocepción , Humanos , Masculino , Propiocepción/fisiología , Adulto Joven , Frecuencia Cardíaca/fisiología , Fatiga Muscular/fisiología , Tobillo/fisiología , Rendimiento Atlético/fisiología , Ácido Láctico/sangre , Ejercicio Pliométrico , Esfuerzo Físico/fisiología
12.
Hum Brain Mapp ; 45(7): e26691, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38703114

RESUMEN

Verbal memory decline is a significant concern following temporal lobe surgeries in patients with epilepsy, emphasizing the need for precision presurgical verbal memory mapping to optimize functional outcomes. However, the inter-individual variability in functional networks and brain function-structural dissociations pose challenges when relying solely on group-level atlases or anatomical landmarks for surgical guidance. Here, we aimed to develop and validate a personalized functional mapping technique for verbal memory using precision resting-state functional MRI (rs-fMRI) and neurosurgery. A total of 38 patients with refractory epilepsy scheduled for surgical interventions were enrolled and 28 patients were analyzed in the study. Baseline 30-min rs-fMRI scanning, verbal memory and language assessments were collected for each patient before surgery. Personalized verbal memory networks (PVMN) were delineated based on preoperative rs-fMRI data for each patient. The accuracy of PVMN was assessed by comparing post-operative functional impairments and the overlapping extent between PVMN and surgical lesions. A total of 14 out of 28 patients experienced clinically meaningful declines in verbal memory after surgery. The personalized network and the group-level atlas exhibited 100% and 75.0% accuracy in predicting postoperative verbal memory declines, respectively. Moreover, six patients with extra-temporal lesions that overlapped with PVMN showed selective impairments in verbal memory. Furthermore, the lesioned ratio of the personalized network rather than the group-level atlas was significantly correlated with postoperative declines in verbal memory (personalized networks: r = -0.39, p = .038; group-level atlas: r = -0.19, p = .332). In conclusion, our personalized functional mapping technique, using precision rs-fMRI, offers valuable insights into individual variability in the verbal memory network and holds promise in precision verbal memory network mapping in individuals.


Asunto(s)
Mapeo Encefálico , Imagen por Resonancia Magnética , Humanos , Femenino , Masculino , Adulto , Adulto Joven , Mapeo Encefálico/métodos , Trastornos de la Memoria/etiología , Trastornos de la Memoria/diagnóstico por imagen , Trastornos de la Memoria/fisiopatología , Persona de Mediana Edad , Epilepsia Refractaria/cirugía , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/fisiopatología , Adolescente , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Red Nerviosa/cirugía , Complicaciones Posoperatorias/diagnóstico por imagen , Procedimientos Neuroquirúrgicos , Aprendizaje Verbal/fisiología , Epilepsia del Lóbulo Temporal/cirugía , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/fisiopatología
13.
Acta Pharmacol Sin ; 45(9): 1861-1878, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38719955

RESUMEN

Pulmonary hypertension (PH) is a progressive fatal disease with no cure. Canagliflozin (CANA), a novel medication for diabetes, has been found to have remarkable cardiovascular benefits. However, few studies have addressed the effect and pharmacological mechanism of CANA in the treatment of PH. Therefore, our study aimed to investigate the effect and pharmacological mechanism of CANA in treating PH. First, CANA suppressed increased pulmonary artery pressure, right ventricular hypertrophy, and vascular remodeling in both mouse and rat PH models. Network pharmacology, transcriptomics, and biological results suggested that CANA could ameliorate PH by suppressing excessive oxidative stress and pulmonary artery smooth muscle cell proliferation partially through the activation of PPARγ. Further studies demonstrated that CANA inhibited phosphorylation of PPARγ at Ser225 (a novel serine phosphorylation site in PPARγ), thereby promoting the nuclear translocation of PPARγ and increasing its ability to resist oxidative stress and proliferation. Taken together, our study not only highlighted the potential pharmacological effect of CANA on PH but also revealed that CANA-induced inhibition of PPARγ Ser225 phosphorylation increases its capacity to counteract oxidative stress and inhibits proliferation. These findings may stimulate further research and encourage future clinical trials exploring the therapeutic potential of CANA in PH treatment.


Asunto(s)
Canagliflozina , Proliferación Celular , Hipertensión Pulmonar , Estrés Oxidativo , PPAR gamma , Animales , Masculino , Ratones , Ratas , Canagliflozina/farmacología , Canagliflozina/uso terapéutico , Proliferación Celular/efectos de los fármacos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/metabolismo , Ratones Endogámicos C57BL , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fosforilación/efectos de los fármacos , PPAR gamma/metabolismo , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/metabolismo , Ratas Sprague-Dawley , Remodelación Vascular/efectos de los fármacos , Serina/química , Serina/metabolismo
14.
Appl Physiol Nutr Metab ; 49(7): 920-932, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38569204

RESUMEN

The aims of this study were (1) to determine how stair-climbing-based exercise snacks (ES) compared to moderate-intensity continuous training (MICT) for improving cardiorespiratory fitness (CRF), and (2) to explore whether ES could improve maximal fat oxidation rate (MFO) in inactive adults. Healthy, young, inactive adults (n: 42, age: 21.6 ± 2.3 years, BMI: 22.5 ± 3.6 kg·m-2, peak oxygen uptake (VO2peak): 33.6 ± 6.3 mL·kg-1·min-1) were randomly assigned to ES, MICT, or Control. ES (n = 14) and MICT (n = 13) groups performed three sessions per week over 6 weeks, while the control group (n = 15) maintained their habitual lifestyle. ES involved 3 × 30 s "all-out" stair-climbing (6 flight, 126 steps, and 18.9 m total height) bouts separated by >1 h rest, and MICT involved 40 min × 60%-70% HRmax stationary cycling. A significant group × time interaction was found for relative VO2peak (p < 0.05) with ES significantly increasing by 7% compared to baseline (MD = 2.5 mL·kg-1·min-1 (95% CI = 1.2, 3.7), Cohen's d = 0.44), while MICT had no significant effects (MD = 1.0 mL·kg-1·min-1 (-1.1, 3.2), Cohen's d = 0.17), and Control experienced a significant decrease (MD = -1.7 mL·kg-1·min-1 (-2.9, -0.4), Cohen's d = 0.26). MFO was unchanged among the three groups (group × time interaction, p > 0.05 for all). Stair climbing-based ES are a time-efficient alternative to MICT for improving CRF among inactive adults, but the tested ES intervention appears to have limited potential to increase MFO.


Asunto(s)
Capacidad Cardiovascular , Ejercicio Físico , Oxidación-Reducción , Consumo de Oxígeno , Bocadillos , Humanos , Masculino , Capacidad Cardiovascular/fisiología , Femenino , Adulto Joven , Consumo de Oxígeno/fisiología , Ejercicio Físico/fisiología , Adulto , Subida de Escaleras/fisiología , Conducta Sedentaria
15.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 41(2): 237-245, 2024 Apr 25.
Artículo en Chino | MEDLINE | ID: mdl-38686403

RESUMEN

The PET/CT imaging technology combining positron emission tomography (PET) and computed tomography (CT) is the most advanced imaging examination method currently, and is mainly used for tumor screening, differential diagnosis of benign and malignant tumors, staging and grading. This paper proposes a method for breast cancer lesion segmentation based on PET/CT bimodal images, and designs a dual-path U-Net framework, which mainly includes three modules: encoder module, feature fusion module and decoder module. Among them, the encoder module uses traditional convolution for feature extraction of single mode image; The feature fusion module adopts collaborative learning feature fusion technology and uses Transformer to extract the global features of the fusion image; The decoder module mainly uses multi-layer perceptron to achieve lesion segmentation. This experiment uses actual clinical PET/CT data to evaluate the effectiveness of the algorithm. The experimental results show that the accuracy, recall and accuracy of breast cancer lesion segmentation are 95.67%, 97.58% and 96.16%, respectively, which are better than the baseline algorithm. Therefore, it proves the rationality of the single and bimodal feature extraction method combining convolution and Transformer in the experimental design of this article, and provides reference for feature extraction methods for tasks such as multimodal medical image segmentation or classification.


Asunto(s)
Algoritmos , Neoplasias de la Mama , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Redes Neurales de la Computación , Aprendizaje Automático , Interpretación de Imagen Asistida por Computador/métodos
16.
bioRxiv ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38617269

RESUMEN

Neutrophils accumulate early in tissue injury. However, the cellular and functional heterogeneity of neutrophils during homeostasis and in response to tissue damage remains unclear. Here, we use larval zebrafish to understand neutrophil responses to thermal injury. Single-cell transcriptional mapping of myeloid cells during a 3-day time course in burn and control larvae revealed distinct neutrophil subsets and their cell-cell interactions with macrophages across time and conditions. The trajectory formed by three zebrafish neutrophil subsets resembles human neutrophil maturation, with varying transition patterns between conditions. Through ligand-receptor cell-cell interaction analysis, we found neutrophils communicate more in burns in a pathway and temporal manner. Finally, we identified the correlation between zebrafish myeloid signatures and human burn severity, establishing GPR84+ neutrophils as a potential marker of early innate immune response in burns. This work builds the molecular foundation and a comparative single-cell genomic framework to identify neutrophil markers of tissue damage using model organisms.

17.
Echocardiography ; 41(3): e15802, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38527007

RESUMEN

The right sinus of the Valsalva aneurysm (SVA) rupturing into the right atrium (RA) and dissecting into the interventricular septum (IVS) is rare. The disease can be definitively diagnosed using two-dimensional (2D) echocardiography and color Doppler ultrasonography. Real-time biplane imaging and three-dimensional (3D) echocardiography offer new perspectives for viewing and diagnosing this disease.


Asunto(s)
Aneurisma Roto , Aneurisma de la Aorta , Disección Aórtica , Rotura de la Aorta , Seno Aórtico , Tabique Interventricular , Humanos , Aneurisma de la Aorta/complicaciones , Aneurisma de la Aorta/diagnóstico por imagen , Seno Aórtico/diagnóstico por imagen , Atrios Cardíacos/diagnóstico por imagen
18.
Arab J Gastroenterol ; 25(2): 84-92, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38403493

RESUMEN

BACKGROUND AND STUDY AIMS: Minimal hepatic encephalopathy (MHE) is an early stage of hepatic encephalopathy (HE) and is highly prevalent. The efficacy of L-ornithine L-aspartate (LOLA) for the treatment of HE is well known but its role in MHE remains uncertain. The objectives of the current study were to evaluate the efficacy of LOLA for the treatment of MHE in patients with cirrhosis. METHODS: The Cochrane Library, PubMed, EMBASE, Web of Science and Ovid databases were searched. Only randomized controlled trials (RCTs) that compared the efficacy of LOLA with placebo or no intervention for the treatment of MHE in patients with cirrhosis were included from inception to January 2023. The primary outcomes were reversal of MHE and development of overt hepatic encephalopathy (OHE). RESULTS: Overall, six RCTs comprising 292 patients were included. Compared with placebo or no intervention, LOLA was more effective in reversing MHE (RR = 2.264, 95 % CI = 1.528, 3.352, P = 0.000, I2 = 0.0 %) and preventing progression of OHE (RR = 0.220, 95 % CI = 0.076, 0.637, P = 0.005, I2 = 0.0 %). Based on subgroup analyses, oral LOLA treatment appeared more likely to reverse MHE (RR = 2.648, 95 % CI = 1.593, 4.402, P = 0.000, I2 = 0.0 %), intravenous LOLA treatment yielded a similar probability of reversing MHE (RR = 1.669, 95 % CI = 0.904, 3.084, P = 0.102, I2 = 0.0 %). LOLA did not show a superior possibility in reducing mortality (RR = 0.422, 95 % CI = 0.064, 2.768, P = 0.368, I2 = 0.0 %) and ammonia levels (SMD = 0.044, 95 % CI = -0.290, 0.379, P = 0.795, I2 = 0.0 %) compared with placebo or no intervention. CONCLUSIONS: LOLA has significant beneficial effects on reversal of MHE and prevention of OHE in patients with cirrhosis compared with placebo or no intervention.


Asunto(s)
Dipéptidos , Encefalopatía Hepática , Cirrosis Hepática , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Dipéptidos/uso terapéutico , Encefalopatía Hepática/tratamiento farmacológico , Encefalopatía Hepática/etiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Resultado del Tratamiento
19.
Vaccines (Basel) ; 12(2)2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38400198

RESUMEN

Zika virus (ZIKV) is an emerging flavivirus that causes congenital syndromes including microcephaly and fetal demise in pregnant women. No commercial vaccines against ZIKV are currently available. We previously generated a chimeric ZIKV (ChinZIKV) based on the Chaoyang virus (CYV) by replacing the prME protein of CYV with that of a contemporary ZIKV strain GZ01. Herein, we evaluated this vaccine candidate in a mouse model and showed that ChinZIKV was totally safe in both adult and suckling immunodeficient mice. No viral RNA was detected in the serum of mice inoculated with ChinZIKV. All of the mice inoculated with ChinZIKV survived, while mice inoculated with ZIKV succumbed to infection in 8 days. A single dose of ChinZIKV partially protected mice against lethal ZIKV challenge. In contrast, all the control PBS-immunized mice succumbed to infection after ZIKV challenge. Our results warrant further development of ChinZIKV as a vaccine candidate in clinical trials.

20.
J Clin Transl Hepatol ; 12(1): 91-99, 2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38250469

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition with limited treatment options. Inflammation caused by metabolic disturbances plays a significant role in NAFLD development. Stimulator of interferon gene (STING), a critical regulator of innate immunity, induces the production of interferons and other pro-inflammatory factors by recognizing cytoplasmic DNA to defend against pathogen infection. The STING-mediated signaling pathway appears to play a vital role in hepatic inflammation, metabolic disorders, and even carcinogenesis. Promisingly, pharmacological interventions targeting STING have shown improvements in the pathological state of NAFLD. Macrophages, dendritic cells, natural killer cells, and T cell pathways regulated by STING present potential novel druggable targets for NAFLD treatment. Further research and development in this area may offer new therapeutic options for managing NAFLD effectively.

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