Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 285
Filtrar
1.
3D Print Addit Manuf ; 11(3): e1394-e1406, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39359609

RESUMEN

In recent years, the application of 3D printing technology in the energetic materials field has proved its ability to innovate traditional charging methods and fabricate complex structures to improve combustion/detonation performance. The melt extrusion technology is the most promising way to fabricate complex structures and multiple components of melt-cast explosives. In this study, a paraffine-based composite was used to substitute melt-cast explosives, and a Design of Experiments approach based on central composite design was adopted to investigate the influence of layer thickness, percent infill, extrusion temperature, and printing velocity on the roughness of printed samples. The results showed that layer thickness and printing velocity could significantly influence the roughness of printed specimens, and no obvious voids or cracks inside the specimens can be detected in computed tomography. In addition, a composite-shaped grain was successfully fabricated via the EAM-D-1 printer, which proved the feasibility of 3D printing melt-cast explosives with complex structures. This work will greatly help to achieve 3D printing melt-cast explosives with complex structures and higher accuracy.

2.
Digit Health ; 10: 20552076241287842, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39376945

RESUMEN

Purpose: The objective of this study was to assess the accuracy of FreeStyle Libre Pro (FSL-Pro) flash continuous glucose monitoring (CGM) in patients with type 2 diabetes mellitus (T2DM) and acute myocardial infarction (AMI). Methods: A single-arm, single-center prospective study was conducted in the cardiac care unit from January 2021 to September 2023. Patients underwent finger-prick blood glucose (FPBG) testing before breakfast (6:00 am) and after meals (at 9:00, 13:00, 19:00 pm), along with CGM during their hospitalization. Statistical analyses included mean differences (MDs), mean absolute relative difference (MARDs) of blood glucose levels, and hypoglycemia occurrences. A Bland-Altman plot analysis and Pearson correlation were performed. Results: Ninety-seven T2DM and AMI patients underwent CGM for up to 72 h (1142 monitoring point). Mean daily BG, Fasting plasma glucose (FPG) and mean postprandial plasma glucose (PPG) were significantly lower by CGM than by FPBG with an estimated MD of -0.89 mmol/L in BG, -0.88 mmol/L in FPG, and -0.90 mmol/L in PPG, respectively. The maximum effect was mainly in the first day and then the difference was gradually declined (falling range, Day1, -1.24; Day 2, -0.70; Day 3, -0.68, mmol/L, respectively). The incidence rates of hypoglycemia and potential hypoglycemia was 1.57% and 8.5% higher, respectively, in CGM than in FBPG. A Bland-Altman Plot revealed some variability and bias between the two methods of measurement of glucose monitoring (p < .001). Pearson's correlation coefficient demonstrated a significant correlation between the mean BG, FPG, and PPG of CGM and FBPG (Pearson's coefficient: 0.92, 0.87, 0.92, respectively, p < .001). Conclusion: Compared with FPBG, FSL Pro-CGM showed lower mean glucose and higher hypoglycemia detection in T2DM and AMI patients, especially in the first 24 h.

3.
Neurol Sci ; 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39382625

RESUMEN

BACKGROUND: Large Hemispheric Infarction (LHI) is a devastating disease with high mortality. This study aimed to use electroencephalography (EEG) to evaluate the death risk of LHI patients and identify suitable evaluation time. METHODS: This study retrospectively collected clinical and EEG data from 73 LHI patients, dividing them into death and survival group at discharge. EEG data was classified as 1-5 days and 6-14 days after onset according to the time intervals of cerebral edema. Regression and receiver operator characteristic curve (ROC) analysis were applied to explore the impact of temporal changes in various EEG and clinical features on death. RESULTS: The areas under ROC curve (AUC) of death prediction for non-α frequency on non-infarct side at 6-14 days after onset was significantly higher than that at 1-5 days (p = 0.004). And there was no significant difference between the AUC of seizure activity for death prediction at 1-5 days and 6-14 days (p = 0.418). Multivariate regression analysis revealed that non-α frequency on non-infarct side and seizure activity at 6-14 days after onset were the independent risk factors for the death of LHI patients. Additionally, above two EEG features significantly improved the death predictive efficacy of clinical features in LHI patients with the integrated discrimination improvement index (IDI) of 0.174 (p = 0.015) and the net reclassification improvement (NRI) of 1.314 (p<0.001). CONCLUSIONS: Non-α frequency on non-infarct side and seizure activity were reliable indicators for death prediction. 6-14 days after onset was the better time window for death evaluation of LHI patients through EEG.

4.
BMC Womens Health ; 24(1): 531, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39334107

RESUMEN

BACKGROUND: Uterine Fibroids (UFs) are common benign tumors in the female reproductive tract, but their progression to intravascular leiomyomatosis (IVL) is rare. Presently, there are few reports on single-stage resection of UFs and IVL. CASE PRESENTATION: A 47-year-old woman, G2P2, had been diagnosed multiple UFs four years ago and now developed heart failure. Imaging examinations revealed that UFs had invaded the right iliac vein and extended into the right atrium through the inferior vena cava. Through multidisciplinary collaboration and a single-stage resection, the patient has survived for over 24 months post-surgery, and her heart function has significantly improved compared to preoperative levels, with no recurrence of UFs observed. CONCLUSIONS: Single-stage resection of IVL and UF is feasible and advantageous for this case, and selecting the appropriate surgical approach is crucial.


Asunto(s)
Leiomioma , Leiomiomatosis , Neoplasias Uterinas , Humanos , Femenino , Persona de Mediana Edad , Leiomiomatosis/cirugía , Leiomiomatosis/patología , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/patología , Leiomioma/cirugía , Leiomioma/patología , Leiomioma/diagnóstico , Vena Cava Inferior/cirugía , Vena Cava Inferior/patología , Neoplasias Vasculares/cirugía , Neoplasias Vasculares/diagnóstico , Vena Ilíaca/cirugía , Atrios Cardíacos/cirugía , Atrios Cardíacos/patología , Atrios Cardíacos/diagnóstico por imagen
5.
Fish Shellfish Immunol ; 154: 109877, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39245185

RESUMEN

cAMP response element binding (CREB) protein 2 (CRTC2) is a transcriptional coactivator of CREB and plays an important role in the immune system. Thus far, the physiological roles of Crtc2 in teleost are still poorly understood. In this study, the crtc2 gene was identified and characterized from yellow catfish (Pelteobagrus fulvidraco; therefore, the gene is termed as pfcrtc2), and its evolutionary and molecular characteristics as well as potential immunity-related roles were investigated. Our results showed that the open reading frame of pfcrtc2 was 2346 bp in length, encoding a protein with 781 amino acids. Gene structure analysis revealed its existence of 14 exons and 13 introns. A phylogenetic analysis proved that the tree of crtc2 was clustered into five groups, exhibiting a similar evolutionary topology with species evolution. Multiple protein sequences alignment demonstrated high conservation of the crtc2 in various vertebrates with similar structure. Syntenic and gene structural comparisons further established that crtc2 was highly conserved, implying its similar roles in diverse vertebrates. Tissue distribution pattern detected by quantitative real-time PCR showed that the pfcrtc2 gene was almost expressed in all detected tissues except for eyes, with the highest expression levels in the gonad, indicating that Crtc2 may play important roles in various tissues. In addition, pfcrtc2 was transcribed at all developmental stages in yellow catfish, showing the highest expression levels at 12 h after fertilization. Finally, the transcriptional profiles of crtc2 were significantly increased in yellow catfishes injected with Aeromonas hydrophila or Poly I:C, which shared a consistent change pattern with four immune-related genes including IL-17A, IL-10, MAPKp38, and NF-κBp65, suggesting pfCrtc2 may play critical roles in preventing both exogenous bacteria and virus invasion. In summary, our findings lay a solid foundation for further studies on the functions of pfcrtc2, and provide novel genetic loci for developing new strategies to control disease outbreak in teleost.

6.
Artículo en Inglés | MEDLINE | ID: mdl-39298550

RESUMEN

Renal denervation (RDN) has been used for treating resistant hypertension. A few recent studies show vagal innervation of kidneys causing confusion. This study aimed to provide anatomical and functional evidence for renal autonomic innervation. Experiments were performed in male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Pseudorabies virus (PRV) in paraventricular nucleus and rostral ventrolateral medulla was prevented by bilateral RDN, but not subdiaphragmatic vagotomy. PRV did not appear in dorsal motor nucleus of vagus and nucleus tractus solitarii 72 h after renal injection of PRV. Adrenergic fibers were approximately 7 times more than cholinergic fibers in main renal artery (MRA) and its first (1RA) and second grade (2RA) branches. Adrenergic fibers in 1RA were more than these in MRA and 2RA. Tyrosine hydroxylase immunoreactivity in these arteries was higher in SHR than WKY. Norepinephrine (NE) increased, and α-receptor antagonist reduced vascular ring tension of renal arteries. The effect of NE was greater in 1RA and 2RA than MRA, which was prevented by α-receptor antagonist. Acetylcholine (ACh) or blockage of ß-receptors, M- or N-receptors had no significant effects on vascular ring tension and the effect of NE. Renal blood flow was reduced by electrical stimulation of renal nerves, but not affected by stimulation of subdiaphragmatic vagus. These results provide anatomical and functional evidence that kidneys are innervated and renal blood flow is regulated by renal sympathetic nerves rather than vagus. Renal vasoconstriction is regulated by NE and adrenergic fibers rather than ACh or cholinergic fibers in WKY and SHR.

7.
J Hepatocell Carcinoma ; 11: 1519-1539, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39139735

RESUMEN

Background: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, underscoring the need for novel therapeutic targets. This study aimed to elucidate the role of endoplasmic reticulum membrane protein complex subunit 1 (EMC1) in HCC progression and its therapeutic potential. Methods: Publicly available sequencing data and biopsy specimens were analyzed to assess EMC's clinical value and functions in HCC. In vitro experiments validated EMC functions, and multiplex immunofluorescence analysis examined EMC-associated sorafenib resistance mechanisms. EMC1 expression was knocked down in HCC cell lines, followed by cell viability, wound healing, and transwell migration assays. Tumor growth and response to sorafenib treatment were evaluated in mouse models. Metabolomic analysis assessed changes in the TCA cycle. Results: EMC genes were aberrantly expressed in HCC, and high EMC1 expression correlated with poorer survival rates. EMC1 disruption enhanced HCC cells' sensitivity to sorafenib, reducing cell viability, increasing apoptosis, and decreasing tumor size and weight. EMC1 maintained cancer cell stemness and promoted M2 macrophage infiltration. Metabolomic analysis revealed significant changes in the TCA cycle, indicating EMC1's role in HCC metabolic reprogramming. Importantly, EMC1 is highly associated with sorafenib resistance, potentially linked to CTNNB1 mutation or activation. Conclusion: EMC1 plays a critical role in regulating the sorafenib resistance in HCC. Targeting EMC1 may improve HCC treatment efficacy.

8.
Environ Sci Technol ; 58(32): 14575-14584, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39094193

RESUMEN

The chromogenic reaction between 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) and ferrate [Fe(VI)] has long been utilized for Fe(VI) content measurement. However, the presence of electron-rich organic compounds has been found to significantly impact Fe(VI) detection using the ABTS method, leading to relative errors ranging from ∼88 to 100%. Reducing substances consumed ABTS•+ and resulted in underestimated Fe(VI) levels. Moreover, the oxidation of electron-rich organics containing hydroxyl groups by Fe(VI) could generate a phenoxyl radical (Ph•), promoting the transformation of Fe(VI) → Fe(V) → Fe(IV). The in situ formation of Fe(IV) can then contribute to ABTS oxidation, altering the ABTS•+:Fe(VI) stoichiometry from 1:1 to 2:1. To overcome these challenges, we introduced Mn(II) as an activator and 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic agent for Fe(VI) detection. This Mn(II)/TMB method enables rapid completion of the chromogenic reaction within 2 s, with a low detection limit of approximately 4 nM and a wide detection range (0.01-10 µM). Importantly, the Mn(II)/TMB method exhibits superior resistance to reductive interference and effectively eliminates the impact of phenoxyl-radical-mediated intermediate valence iron transfer processes associated with electron-rich organic compounds. Furthermore, this method is resilient to particle interference and demonstrates practical applicability in authentic waters.


Asunto(s)
Electrones , Oxidación-Reducción , Hierro/química , Compuestos Orgánicos/química , Benzotiazoles/química , Ácidos Sulfónicos
9.
World J Clin Cases ; 12(18): 3360-3367, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38983425

RESUMEN

BACKGROUND: Although chemotherapy is effective for treating advanced gastric carcinoma (aGC), it may lead to an adverse prognosis. Establishing a highly effective and low-toxicity chemotherapy regimen is necessary for improving efficacy and outcomes in aGC patients. AIM: To determine the efficacy and safety of cetuximab (CET) combined with the FOLFOX4 regimen (infusional fluorouracil, folinic acid, and oxaliplatin) as first-line therapy for patients with aGC, who received evidence-based care (EBC). METHODS: A total of 117 aGC patients who received EBC from March 2019 to March 2022 were enrolled. Of these, 60 in the research group (RG) received CET + FOLFOX4 as first-line therapy, whereas 57 in the control group (CG) received FOLFOX4. The efficacy [clinical response rate (RR) and disease control rate (DCR)], safety (liver and kidney dysfunction, leukopenia, thrombocytopenia, rash, and diarrhea), serum tumor marker expression [STMs; carbohydrate antigen (CA) 19-9, CA72-4, and carcinoembryonic antigen (CEA)], inflammatory indicators [interleukin (IL)-2 and IL-10], and quality of life (QOL) of the two groups were compared. RESULTS: A markedly higher RR and DCR were observed in the RG compared with the CG, with an equivalent safety profile between the two groups. RG exhibited notably reduced CA19-9, CA72-4, CEA, and IL-2 levels following treatment, which were lower than the pre-treatment levels and those in the CG. Post-treatment IL-10 was statistically increased in RG, higher than the pre-treatment level and the CG. Moreover, a significantly improved QOL was evident in the RG. CONCLUSION: The CET + FOLFOX4 regimen is highly effective as first-line treatment for aGC patients receiving EBC. It facilitates the suppression of STMs, ameliorates the serum inflammatory microenvironment, and enhances QOL, without increased adverse drug effects.

10.
Artículo en Inglés | MEDLINE | ID: mdl-39052465

RESUMEN

Motor imagery EEG classification plays a crucial role in non-invasive Brain-Computer Interface (BCI) research. However, the performance of classification is affected by the non-stationarity and individual variations of EEG signals. Simply pooling EEG data with different statistical distributions to train a classification model can severely degrade the generalization performance. To address this issue, the existing methods primarily focus on domain adaptation, which requires access to the test data during training. This is unrealistic and impractical in many EEG application scenarios. In this paper, we propose a novel multi-source domain generalization framework called EEG-DG, which leverages multiple source domains with different statistical distributions to build generalizable models on unseen target EEG data. We optimize both the marginal and conditional distributions to ensure the stability of the joint distribution across source domains and extend it to a multi-source domain generalization framework to achieve domain-invariant feature representation, thereby alleviating calibration efforts. Systematic experiments conducted on a simulative dataset, BCI competition IV 2a, 2b, and OpenBMI datasets, demonstrate the superiority and competitive performance of our proposed framework over other state-of-the-art methods. Specifically, EEG-DG achieves average classification accuracies of 81.79% and 87.12% on datasets IV-2a and IV-2b, respectively, and 78.37% and 76.94% for inter-session and inter-subject evaluations on dataset OpenBMI, which even outperforms some domain adaptation methods. Our code is available at https://github.com/zxchit2022/EEG-DG for evaluation.

11.
Eur J Neurosci ; 60(5): 4830-4842, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39044301

RESUMEN

Chemerin is an adipokine that contributes to metabolism regulation. Nucleus tractus solitarius (NTS) is the first relay station in the brain for accepting various visceral afferent activities for regulating cardiovascular activity. However, the roles of chemerin in the NTS in regulating sympathetic activity and blood pressure are almost unknown. This study aimed to determine the role and potential mechanism of chemerin in the NTS in modulating sympathetic outflow and blood pressure. Bilateral NTS microinjections were performed in anaesthetized adult male Sprague-Dawley rats. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were continuously recorded. Chemerin and its receptor chemokine-like receptor 1 (CMKLR1) were highly expressed in caudal NTS (cNTS). Microinjection of chemerin-9 to the cNTS increased RSNA, MAP and HR, which were prevented by CMKLR1 antagonist α-NETA, superoxide scavenger tempol or N-acetyl cysteine, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors diphenyleneiodonium or apocynin. Chemerin-9 increased superoxide production and NADPH oxidase activity in the cNTS. The increased superoxide production induced by chemerin-9 was inhibited by α-NETA. The effects of cNTS microinjection of chemerin-9 on the RSNA, MAP and HR were attenuated by the pretreatment with paraventricular nucleus (PVN) microinjection of NMDA receptor antagonist MK-801 rather than AMPA/kainate receptor antagonist CNQX. These results indicate that chemerin-9 in the NTS increases sympathetic outflow, blood pressure and HR via CMKLR1-mediated NADPH oxidase activation and subsequent superoxide production in anaesthetized normotensive rats. Glutamatergic inputs in the PVN are needed for the chemerin-9-induced responses.


Asunto(s)
Presión Sanguínea , Quimiocinas , Ratas Sprague-Dawley , Núcleo Solitario , Sistema Nervioso Simpático , Animales , Núcleo Solitario/efectos de los fármacos , Núcleo Solitario/fisiología , Núcleo Solitario/metabolismo , Masculino , Quimiocinas/metabolismo , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Sistema Nervioso Simpático/fisiología , Sistema Nervioso Simpático/efectos de los fármacos , Ratas , Receptores de Quimiocina/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Péptidos y Proteínas de Señalización Intercelular/farmacología , Péptidos y Proteínas de Señalización Intercelular/administración & dosificación , NADPH Oxidasas/metabolismo , Superóxidos/metabolismo
12.
Phytomedicine ; 132: 155792, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39059090

RESUMEN

BACKGROUND: Numerous studies indicate that natural polysaccharides have immune-enhancing effects as a host defense potentiator. Few reports are available on hormetic effects of natural polysaccharides, and the underlying mechanisms remain unclear. PURPOSE: AELP-B6 (arabinose- and galactose-rich pectin polysaccharide) from Aralia elata (Miq.) Seem was taken as a case study to clarify the potential mechanism of hormetic effects of natural polysaccharides. METHODS: The pharmacodynamic effect of AELP-B6 was verified by constructing the CTX-immunosuppressive mouse model. The hormetic effects were explored by TMT-labeled proteomics, energy metabolism analysis, flow cytometry and western blot. The core-affinity target of AELP-B6 was determined by pull down, nanoLC-nanoESI+-MS, CETSA, immunoblot and SPR assay. The RAW264.7Clec4G-RFP and RAW264.7Rab1A-RFP cell lines were simultaneously constructed to determine the affinity difference between AELP-B6 and targets by confocal laser scanning live-cell imaging. Antibody blocking assays were further used to verify the mechanism of hormetic effects. RESULTS: AELP-B6 at low and medium doses may maintain the structural integrity of thymus and spleen, increase the concentrations of TNF-α, IFN-γ, IL-3 and IL-8, and alleviate CTX-induced reduction of immune cell viability in vivo. Proteomics and energy metabolism analysis revealed that AELP-B6 regulate HIF-1α-mediated metabolic programming, causing Warburg effects in macrophages. AELP-B6 at low and medium doses promoted the release of intracellular immune factors, and driving M1-like polarization of macrophages. As a contrast, AELP-B6 at high dose enhanced the expression levels of apoptosis related proteins, indicating activation of the intrinsic apoptotic cascade. Two highly expressed transmembrane proteins in macrophages, Clec4G and Rab1A, were identified as the primary binding targets of AELP-B6 which co-localized with the cell membrane and directly impacted with immune cell activation and apoptosis. AELP-B6 exhibits affinity differences with Clec4G and Rab1A, which is the key to the hormetic effects. CONCLUSION: We observed hormesis of natural polysaccharide (AELP-B6) for the first time, and AELP-B6 mediates the hormetic effects through two dose-related targets. Low dose of AELP-B6 targets Clec4G, thereby driving the M1-like polarization via regulating NF-κB signaling pathway and HIF-1α-mediated metabolic programming, whereas high dose of AELP-B6 targets Rab1A, leading to mitochondria-dependent apoptosis.


Asunto(s)
Pectinas , Animales , Ratones , Pectinas/farmacología , Lectinas Tipo C/metabolismo , Células RAW 264.7 , Metabolismo Energético/efectos de los fármacos , Polisacáridos/farmacología
13.
BMC Cancer ; 24(1): 755, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38907210

RESUMEN

BACKGROUND: The role of hemoglobin (HGB) in common malignant tumors remains unclear. METHODS: A retrospective analysis was conducted to identify the correlation between HGB levels and risk of 15 malignant tumors using 50,085 samples from the National Health and Nutrition Examination Survey. Mendelian Randomization analyses (MRAs) were performed based on genome-wide association study data to assess the causal relationship between HGB levels and these malignant tumors using more than 700,000 samples. The robustness of the MRA results was confirmed through various analytical methods. Fifty-six in-house samples were used to investigate the correlation between HGB levels and the prognosis in prostate cancer (PRCA) using the Kaplan-Meier curve. RESULTS: High HGB levels were associated with a higher risk for patients with cervix cancer, melanoma, and non-melanoma skin cancer (OR > 1.000, p < 0.05). It served as a protective factor for colon cancer, esophagus cancer, stomach cancer, bone cancer, lung cancer, renal cancer, and PRCA (OR < 1.000, p < 0.05). Furthermore, MRAs suggested that elevated HGB levels were correlated with a reduced risk of PRCA (OR = 0.869, p < 0.05), with no significant association observed between this marker and the remaining 14 malignant tumors. No pleiotropy or heterogeneity was found in the ultimate results for MRAs (p-values > 0.05), suggesting the robustness of the results. The results derived from the in-house data revealed a relationship between higher HGB values and a more favorable prognosis in PRCA (p < 0.05). CONCLUSION: High circulating HGB levels may play a protective prognostic role for PRCA and serve as a protective factor against the occurrence of PRCA.


Asunto(s)
Hemoglobinas , Neoplasias , Humanos , Estudios Retrospectivos , Masculino , Femenino , Hemoglobinas/análisis , Neoplasias/epidemiología , Neoplasias/sangre , Neoplasias/genética , Estudio de Asociación del Genoma Completo , Pronóstico , Persona de Mediana Edad , Análisis de la Aleatorización Mendeliana , Factores de Riesgo , Encuestas Nutricionales , Adulto , Anciano , Biomarcadores de Tumor/sangre
14.
J Transl Med ; 22(1): 580, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898490

RESUMEN

The importance of the immune microenvironment in poorly cohesive carcinoma (PCC) has been highlighted due to its limited response rate to conventional therapy and emerging treatment resistance. A combination of clinical cohorts, bioinformatics analyses, and functional/molecular experiments revealed that high infiltration of Interferon Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) + tumor-associated neutrophils (TANs) is a distinguishing feature of PCC patients. Upregulation of IFIT1 + TANs promote migration and invasion of gastric cancer (GC) cell lines (MKN45 and MKN74) and stimulates the growth of cell-derived xenograft models. Besides, by promoting macrophage secreted phosphoprotein 1 (SPP1) expression and facilitating cancer-associated fibroblast and endothelial cell recruitment and activation through TANs, IFIT1 promotes a mesenchymal phenotype, which is associated with a poor prognosis. Importantly, compared to non-PCC (NPCC), PCC tumors is more immunosuppressive. Mechanistically, IFIT1 can be stimulated by IFN-γ and contributes to the expression of Programmed Cell Death 1 Ligand (PDL1) in TANs. We demonstrated in mouse models that IFIT1 + PDL1 + TANs can induce acquired resistance to anti-PD-1 immunotherapy, which may be responsible for the difficulty of PCC patients to benefit from immunotherapy. This work highlights the role of IFIT1 + TANs in mediating the remodeling of the tumor immune microenvironment and immunotherapeutic resistance and introduces IFIT1 + TANs as a promising target for precision therapy of PCC.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Neutrófilos , Proteínas de Unión al ARN , Humanos , Neutrófilos/inmunología , Neutrófilos/metabolismo , Animales , Proteínas de Unión al ARN/metabolismo , Línea Celular Tumoral , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Microambiente Tumoral/inmunología , Femenino , Antígeno B7-H1/metabolismo , Neoplasias Gástricas/patología , Neoplasias Gástricas/inmunología , Masculino , Ratones , Resistencia a Antineoplásicos , Movimiento Celular , Tolerancia Inmunológica , Terapia de Inmunosupresión , Regulación Neoplásica de la Expresión Génica , Invasividad Neoplásica , Ratones Desnudos , Inmunoterapia , Persona de Mediana Edad
15.
BMC Vet Res ; 20(1): 204, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38755662

RESUMEN

Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia (PCP), which is clinically characterized by acute hemorrhagic, necrotizing pneumonia, and chronic fibrinous pneumonia. Although many measures have been taken to prevent the disease, prevention and control of the disease are becoming increasingly difficult due to the abundance of APP sera, weak vaccine cross-protection, and increasing antibiotic resistance in APP. Therefore, there is an urgent need to develop novel drugs against APP infection to prevent the spread of APP. Naringin (NAR) has been reported to have an excellent therapeutic effect on pulmonary diseases, but its therapeutic effect on lung injury caused by APP is not apparent. Our research has shown that NAR was able to alleviate APP-induced weight loss and quantity of food taken and reduce the number of WBCs and NEs in peripheral blood in mice; pathological tissue sections showed that NAR was able to prevent and control APP-induced pathological lung injury effectively; based on the establishment of an in vivo/in vitro model of APP inflammation, it was found that NAR was able to play an anti-inflammatory role through inhibiting the MAPK/NF-κB signaling pathway and exerting anti-inflammatory effects; additionally, NAR activating the Nrf2 signalling pathway, increasing the secretion of antioxidant enzymes Nqo1, CAT, and SOD1, inhibiting the secretion of oxidative damage factors NOS2 and COX2, and enhancing the antioxidant stress ability, thus playing an antioxidant role. In summary, NAR can relieve severe lung injury caused by APP by reducing excessive inflammatory response and improving antioxidant capacity.


Asunto(s)
Infecciones por Actinobacillus , Actinobacillus pleuropneumoniae , Lesión Pulmonar Aguda , Flavanonas , Proteína 1 Asociada A ECH Tipo Kelch , Factor 2 Relacionado con NF-E2 , FN-kappa B , Animales , Ratones , Infecciones por Actinobacillus/veterinaria , Infecciones por Actinobacillus/tratamiento farmacológico , Actinobacillus pleuropneumoniae/efectos de los fármacos , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/prevención & control , Flavanonas/uso terapéutico , Flavanonas/farmacología , Hemo-Oxigenasa 1 , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Proteínas de la Membrana , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos
16.
Medicine (Baltimore) ; 103(14): e37658, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38579057

RESUMEN

To investigate the status quo and influencing factors of general postpartum well-being in primiparas, analyze its correlation with postpartum depression, and provide a theoretical foundation for enhancing the postpartum well-being of primiparas. From the start of November 2021 to the end of December 2021, the General Information Questionnaire, General Well-Being Scale, and the Edinburgh Postpartum Depression Scale were used to survey primiparas in a tertiary hospital, and the correlation between general well-being and postpartum depression was analyzed. We surveyed a total of 225 primiparas. The average score for general well-being in primiparas was 77.84 ±â€…6.83, and the total score for postpartum depression was 9.11 ±â€…2.51. Confinement location, planned pregnancy, pregnancy complications, neonatal sex, medical expenses, etc, had statistically significant effects on the general well-being scores (P < .05), whereas per capita monthly income, pregnancy complications, maternal and infant care skills, and medical expenses had statistically significant effects on postpartum depression scores (P < .05). Postpartum depression scores were negatively correlated with general well-being, health anxiety, energy, sad or happy mood, relaxation, and tension. There is a negative correlation between the general well-being of primiparas and postpartum depression, suggesting that in clinical care, the focus should be on primiparas with pregnancy complications, and psychological counseling should be provided in advance to prevent postpartum depression and the resulting decrease in well-being.


Asunto(s)
Depresión Posparto , Complicaciones del Embarazo , Embarazo , Lactante , Recién Nacido , Femenino , Humanos , Depresión Posparto/epidemiología , Depresión/epidemiología , Estudios Transversales , Periodo Posparto/psicología , Complicaciones del Embarazo/epidemiología
17.
J Neurosci ; 44(21)2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38565292

RESUMEN

Glucagon-like peptide-1 (GLP-1) and its analogs are widely used for diabetes treatment. The paraventricular nucleus (PVN) is crucial for regulating cardiovascular activity. This study aims to determine the roles of GLP-1 and its receptors (GLP-1R) in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male normotensive rats and spontaneously hypertensive rats (SHR). Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. GLP-1 and GLP-1R expressions were present in the PVN. PVN microinjection of GLP-1R agonist recombinant human GLP-1 (rhGLP-1) or EX-4 increased RSNA and MAP, which were prevented by GLP-1R antagonist exendin 9-39 (EX9-39) or GLP-1R antagonist 1, superoxide scavenger tempol, antioxidant N-acetylcysteine, NADPH oxidase (NOX) inhibitor apocynin, adenylyl cyclase (AC) inhibitor SQ22536 or protein kinase A (PKA) inhibitor H89. PVN microinjection of rhGLP-1 increased superoxide production, NADPH oxidase activity, cAMP level, AC, and PKA activity, which were prevented by SQ22536 or H89. GLP-1 and GLP-1R were upregulated in the PVN of SHR. PVN microinjection of GLP-1 agonist increased RSNA and MAP in both WKY and SHR, but GLP-1 antagonists caused greater effects in reducing RSNA and MAP in SHR than in WKY. The increased superoxide production and NADPH oxidase activity in the PVN of SHR were augmented by GLP-1R agonists but attenuated by GLP-1R antagonists. These results indicate that activation of GLP-1R in the PVN increased sympathetic outflow and blood pressure via cAMP-PKA-mediated NADPH oxidase activation and subsequent superoxide production. GLP-1 and GLP-1R upregulation in the PVN partially contributes to sympathetic overactivity and hypertension.


Asunto(s)
Péptido 1 Similar al Glucagón , Receptor del Péptido 1 Similar al Glucagón , Hipertensión , Núcleo Hipotalámico Paraventricular , Ratas Endogámicas SHR , Sistema Nervioso Simpático , Animales , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/metabolismo , Masculino , Hipertensión/fisiopatología , Hipertensión/metabolismo , Ratas , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/fisiología , Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/antagonistas & inhibidores , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Ratas Endogámicas WKY , Ratas Sprague-Dawley
18.
Ann Geriatr Med Res ; 28(3): 273-283, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38651272

RESUMEN

BACKGROUND: Advances in blood biomarker discovery have enabled the improved diagnosis and prognosis of Alzheimer's disease (AD). Most branched-chain amino acids, except isoleucine (Ile), are correlated with both mild cognitive impairment (MCI) and AD. Therefore, this study investigated the association between serum Ile levels and MCI/AD. METHODS: This study stratified 700 participants from the Alzheimer's Disease Neuroimaging Initiative database into four diagnostic groups: cognitively normal, stable MCI, progressive MCI, and AD. Analysis of covariance and chi-square analyses were used to test the demographic data. Receiver operating curve analyses were used to calculate the diagnostic accuracy of different biomarkers and were compared by MedCalc 20. Additionally, Cox proportional hazards models were used to measure the ability of serum Ile levels to predict disease conversion. Finally, a linear mixed-effects model was used to evaluate the associations between serum Ile levels and cognition, brain structure, and metabolism. RESULTS: Serum Ile concentration was decreased in AD and demonstrated significant diagnostic efficacy. The combination of serum Ile and cerebrospinal fluid (CSF) phosphorylated tau (P-tau) improved the diagnostic accuracy in AD compared to total tau (T-tau) alone. Serum Ile levels significantly predicted the conversion from MCI to AD (cutoff value of 78.3 µM). Finally, the results of this study also revealed a correlation between serum Ile levels and the Alzheimer's Disease Assessment Scale cognitive subscale Q4. CONCLUSIONS: Serum Ile may be a potential biomarker of AD. Ile had independent diagnostic efficacy and significantly improved the diagnostic accuracy of CSF P-tau in AD. MCI patients with a lower serum Ile level had a higher risk of progression to AD and a worse cognition assessment.


Asunto(s)
Enfermedad de Alzheimer , Biomarcadores , Disfunción Cognitiva , Isoleucina , Proteínas tau , Humanos , Disfunción Cognitiva/sangre , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/líquido cefalorraquídeo , Femenino , Isoleucina/sangre , Isoleucina/líquido cefalorraquídeo , Masculino , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/líquido cefalorraquídeo , Anciano , Biomarcadores/sangre , Proteínas tau/sangre , Proteínas tau/líquido cefalorraquídeo , Progresión de la Enfermedad , Anciano de 80 o más Años , Modelos de Riesgos Proporcionales
19.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(3): 258-261, 2024 Mar 15.
Artículo en Chino | MEDLINE | ID: mdl-38557377

RESUMEN

OBJECTIVES: To evaluate the incidence rate of Duchenne muscular dystrophy (DMD) in the male newborns in the Ningxia region and establish a critical threshold for screening DMD in newborns to distinguish between the normal population and affected individuals. METHODS: A total of 10 000 male newborns were screened using immunofluorescence analysis of creatine kinase isoenzyme concentrations in heel spot dried blood specimens. Newborns with the concentrations higher than the critical threshold were recalled for serum creatine kinase measurements. Genetic testing was performed to confirm diagnosis in cases showing abnormalities. RESULTS: Among the screened 10 000 male newborns, two were confirmed to have DMD through genetic testing, resulting in a preliminary estimated incidence rate of 1/5 000 for male newborns in the Ningxia region. The critical threshold for creatine kinase isoenzyme concentration in newborns in this region was determined to be 468.57 ng/mL. CONCLUSIONS: Screening for DMD in newborns is feasible in the Ningxia region. Early screening, diagnosis, and treatment of DMD can improve the quality of life for affected individuals and help families make informed decisions regarding further pregnancies.


Asunto(s)
Distrofia Muscular de Duchenne , Humanos , Masculino , Recién Nacido , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Isoenzimas , Calidad de Vida , Tamizaje Neonatal/métodos , Creatina Quinasa
20.
BMC Psychiatry ; 24(1): 331, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38689265

RESUMEN

BACKGROUND: To examine the factor structure and psychometric properties of the Patient Health Questionnaire for Adolescents (PHQ-A) in Chinese children and adolescents with major depressive disorder (MDD). METHODS: A total of 248 MDD patients aged between 12 and 18 years were recruited and evaluated by the Patient Health Questionnaire for Adolescents (PHQ-A), the Center for Epidemiological Survey Depression Scale (CES-D), the Mood and Feelings Questionnaire (MFQ), and the improved Clinical Global Impression Scale, Severity item (iCGI-S). Thirty-one patients were selected randomly to complete the PHQ-A again one week later. Confirmatory factor analysis (CFA) was used to test the construct validity of the scale. Reliability was evaluated by Macdonald Omega coefficient. Pearson correlation coefficient was used to assess the item-total correlation and the correlation of PHQ-A with CES-D and MFQ respectively. Spearman correlation coefficient was used to assess test-retest reliability. The optimal cut-off value, sensitivity, and specificity of the PHQ-A were achieved by estimating the Receiver Operating Characteristics (ROC) curve. RESULTS: CFA reported adequate loadings for all items, except for item 3. Macdonald Omega coefficient of the PHQ-A was 0.87. The Spearman correlation coefficient of the test-retest reliability was 0.70. The Pearson correlation coefficients of the PHQ-A with CES-D and MFQ were 0.87 and 0.85, respectively (p < 0.01). By taking the iCGI-S as the remission criteria for MDD, the optimal cut-off value, sensitivity and specificity of the PHQ-A were 7, 98.7%, 94.7% respectively. CONCLUSION: The PHQ-A presented as a unidimensional construct and demonstrated satisfactory reliability and validity among the Chinese children and adolescents with MDD. A cut-off value of 7 was suggested for remission.


Asunto(s)
Trastorno Depresivo Mayor , Psicometría , Humanos , Adolescente , Masculino , Femenino , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Reproducibilidad de los Resultados , Niño , China , Análisis Factorial , Cuestionario de Salud del Paciente , Encuestas y Cuestionarios/normas , Escalas de Valoración Psiquiátrica/normas , Sensibilidad y Especificidad , Pueblo Asiatico/psicología , Pueblos del Este de Asia
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA