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1.
J Cardiovasc Nurs ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38622773

RESUMO

BACKGROUND: Previous research has examined the dyadic health components consisting of dyadic burdens, psychological disorders, psychological resilience, and illness- or caregiving-related beliefs independently from each other in patients with chronic heart failure (CHF) and their caregivers, but there is a need for further insights into their interconnections. OBJECTIVE: We aimed to explore the interconnections among dyadic health components in patients with CHF and their caregivers. METHODS: We conducted a cross-sectional study, recruiting in a total of 355 patients with CHF and their 355 respective caregivers, totaling 710 individuals across the dyads. Assessments were conducted on symptom burden, caregiver burden, anxiety, depression, psychological resilience, perceived control, and caregiver self-efficacy. Network analysis was used regarding these constructs as nodes and their associations as edges. RESULTS: The strongest edge weight was observed between patients' anxiety and depression, followed by caregivers' anxiety and depression. Patients' depression exhibited the strongest edge weight with dyadic burdens. Caregiver burden was independently correlated with all nodes. Patients' symptom burden had fewer associations with the nodes within the caregiver community. Patients' anxiety, depression, and psychological resilience demonstrated the strongest and most influential correlations with other nodes. CONCLUSIONS: The findings illustrated extensive interconnections among dyadic health components in CHF dyads. These findings underscored the significance of managing and intervening with patients and caregivers as a dyadic whole. Given the strong and frequent associations of patients' anxiety, depression, and psychological resilience with other nodes in the network, interventions targeting these nodes may enhance the overall network health of CHF dyads.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38563809

RESUMO

Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by epidermal thickening and inflammatory cell infiltration. Excessive proliferation of keratinocytes and resistance to apoptosis lead to thickening of the epidermis. Plasmacytoid dendritic cells are involved in the occurrence of psoriasis mainly by secreting interferon-alpha (IFN-α). IFN-α is a glycoprotein with antiviral, antitumor, and immunomodulatory effects, but its role in psoriasis remains unclear. In this investigation, a mild psoriatic phenotype was observed in mice upon topical application of IFN-α cream, and the inflammation was exacerbated when combined with imiquimod (IMQ). Immunohistochemical analyses demonstrated that IFN-α induces psoriatic inflammation in mice by stimulating phosphorylation of forkhead box O3, consistent with the involvement of this protein in cell proliferation, apoptosis, and inflammation. Our results suggested that topical IFN-α caused psoriatic inflammation and that the psoriatic inflammation was exacerbated by the combination of IFN-α and IMQ, possibly due to the dysfunction of forkhead box O3.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38604119

RESUMO

Electrochemical reduction of CO2 to value-added products provides a feasible pathway for mitigating net carbon emissions and storing renewable energy. However, the low dimerization efficiency of the absorbed CO intermediate (*CO) and the competitive hydrogen evolution reaction hinder the selective electroreduction of CO2 to ethane (C2H6) with a high energy density. Here, we designed hydrophobic iodide-derived copper electrodes (I-Cu/Nafion) for reducing CO2 to C2H6. The Faradaic efficiency of C2H6 reached 23.37% at -0.7 V vs RHE over the I-Cu/Nafion electrode in an H-type cell, which was about 1.7 times higher than that of the I-Cu electrode. The hydrophobic properties of the I-Cu/Nafion electrodes led to an increase in the local CO2 concentration and stabilized the Cu+ species. In situ Raman characterizations and density functional theory calculations indicate that the enhanced performances could be ascribed to the strong *CO adsorption and decreased the formation energy of *COOH and *COCOH intermediates. This study highlights the effect of the hydrophobic surface on Cu-based catalysts in the electroreduction of CO2 and provides a promising way to adjust the selectivity of C2 products.

4.
Cell Stem Cell ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38593797

RESUMO

Many patient-derived tumor models have emerged recently. However, their potential to guide personalized drug selection remains unclear. Here, we report patient-derived tumor-like cell clusters (PTCs) for non-small cell lung cancer (NSCLC), capable of conducting 100-5,000 drug tests within 10 days. We have established 283 PTC models with an 81% success rate. PTCs contain primary tumor epithelium self-assembled with endogenous stromal and immune cells and show a high degree of similarity to the original tumors in phenotypic and genotypic features. Utilizing standardized culture and drug-response assessment protocols, PTC drug-testing assays reveal 89% overall consistency in prospectively predicting clinical outcomes, with 98.1% accuracy distinguishing complete/partial response from progressive disease. Notably, PTCs enable accurate prediction of clinical outcomes for patients undergoing anti-PD1 therapy by combining cell viability and IFN-γ value assessments. These findings suggest that PTCs could serve as a valuable preclinical model for personalized medicine and basic research in NSCLC.

5.
iScience ; 27(4): 109518, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38585662

RESUMO

Herbivorous insects have evolved metabolic strategies to survive the challenges posed by plant secondary metabolites (SMs). This study reports an exploration of SMs present in pears, which serve as a defense against invasive Cydia pomonella and native Grapholita molesta and their counter-defense response. The feeding preferences of fruit borers are influenced by the softening of two pear varieties as they ripen. The content of SMs, such as quercetin and rutin, increases due to feeding by fruit borers. Notably, quercetin levels only increase after C. pomonella feeding. The consumption of SMs affects the growth of fruit borer population differently, potentially due to the activation of P450 genes by SMs. These two fruit borers are equipped with specific P450 enzymes that specialize in metabolizing quercetin and rutin, enabling them to adapt to these SMs in their host fruits. These findings provide valuable insights into the coevolution of plants and herbivorous insects.

6.
Alzheimers Res Ther ; 16(1): 82, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615037

RESUMO

BACKGROUND: Previous studies have demonstrated that early intervention was the best plan to inhibit the progression of Alzheimer's disease (AD), which relied on the discovery of early diagnostic biomarkers. In this study, synaptic vesicle glycoprotein 2 A (SV2A) was examined to improve the early diagnostic efficiency in AD. METHODS: In this study, biomarker testing was performed through the single-molecule array (Simoa). A total of 121 subjects including cognitively unimpaired controls, amnestic mild cognitive impairment (aMCI), AD and other types of dementia underwent cerebrospinal fluid (CSF) SV2A testing; 430 subjects including health controls, aMCI, AD and other types of dementia underwent serum SV2A, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL) and p-tau217 testing; 92 subjects including aMCI and AD underwent both CSF SV2A and serum SV2A testing; 115 cognitively unimpaired subjects including APOE ε4 carriers and APOE ε4 non-carriers were tested for serum SV2A, GFAP, NfL and p-tau217. Then, the efficacy of SV2A for the early diagnosis of AD and its ability to identify those at high risk of AD from a cognitively unimpaired population were further analyzed. RESULTS: Both CSF and serum SV2A significantly and positively correlated with cognitive performance in patients with AD, and their levels gradually decreased with the progression of AD. Serum SV2A demonstrated excellent diagnostic efficacy for aMCI, with a sensitivity of 97.8%, which was significantly higher than those of NfL, GFAP, and p-tau217. The SV2A-positive rates ranged from 92.86 to 100% in aMCI cases that were negative for the above three biomarkers. Importantly, of all the biomarkers tested, serum SV2A had the highest positivity rate (81.82%) in individuals at risk for AD. CONCLUSIONS: Serum SV2A was demonstrated to be a novel and ideal biomarker for the early diagnosis of AD, which can effectively distinguish those at high risk of AD in cognitively unimpaired populations.


Assuntos
Doença de Alzheimer , Glicoproteínas de Membrana , Proteínas do Tecido Nervoso , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Apolipoproteína E4 , Biomarcadores , Diagnóstico Precoce , Glicoproteínas , Vesículas Sinápticas/química , Vesículas Sinápticas/metabolismo , Glicoproteínas de Membrana/líquido cefalorraquidiano , Glicoproteínas de Membrana/química , Proteínas do Tecido Nervoso/líquido cefalorraquidiano , Proteínas do Tecido Nervoso/química
7.
Ecotoxicol Environ Saf ; 276: 116328, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38636262

RESUMO

BACKGROUND: The relationships between maternal genetic and environmental exposure and conotruncal heart defects (CTDs) have been extensively investigated. Nevertheless, there is limited knowledge regarding the impact of ozone (O3) on the risk of CTDs. OBJECTIVE: To explore the correlation between maternal exposure to O3 and CTDs in China. METHODS: Pregnant women who underwent fetal echocardiography at Beijing Anzhen Hospital between January 2013 and December 2021 were enrolled. Their sociodemographic characteristics and lifestyle information, along with fetal data, were systematically collected. Fetal echocardiography was used to detect CTDs. Maternal exposure to ambient O3 during the embryonic period, the first trimester, the three months preceding the last menstrual period, and the perinatal period was estimated using residential addresses or hospital addresses associated with prenatal visits. The concentration of O3 was divided by quartiles, with the first quartile serving as a reference. Adjusted logistic regression models were employed to examine the associations between every 10 µg/m3 increase or quartile increase in ambient O3 exposure and CTDs. RESULTS: Among 24,278 subjects, 1069 exhibited fetuses with CTDs. Maternal exposure to ambient O3 during three pregnancy periods was associated with increased CTD risk. The adjusted odds ratio (OR) and 95% confidence interval (CI) were 1.271 (1.189-1.360) per 10 µg/m3 increase in O3 during the perinatal period. For each quartile of O3, the risk increased with increasing exposure concentration, particularly during the perinatal period (OR = 2.206 for quartile 2, 2.367 for quartile 3, and 3.378 for quartile 4, all P<0.05). CONCLUSIONS: Elevated maternal exposure to O3 during pregnancy, particularly in the perinatal period, is linked to an increased risk of fetal CTDs. Further longitudinal analyses are needed to validate these results.

8.
Aging Ment Health ; : 1-10, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566487

RESUMO

OBJECTIVES: The built environment is increasingly recognized as being associated with late-life loneliness. However, the pathway remains understudied. This study investigated the mediating effects of productive engagement in relationships between the built environment and loneliness. METHODS: We conducted a cross-sectional analysis of data from 4,409 community-dwelling people aged 65 years and above in China. We employed the Chinese version of the De Jong Gierveld Loneliness Scale to assess loneliness. The built environment comprises residential density, street connectivity, park-based and vegetation-based green space, land use mix, and the number of and distance to the nearest recreational, health, shopping and community services within 300-meter and 500-meter buffer areas. Structural equation modeling was used. RESULTS: Only green space (parks) had a direct effect on loneliness. Residential density and green space (parks) had an indirect effect on loneliness through volunteering. The number of recreational services had an indirect effect on loneliness through recreational and sporting activities, although distance to the nearest recreational services did not. All the significant results were only found within 300-meter rather than 500-meter buffers. CONCLUSIONS: Our findings have implications for environmental gerontology theory and practice. Providing more green space and recreational services can significantly improve older adults' helping behavior, social activities and sporting activities, which can further reduce older adults' loneliness.

9.
J Cardiovasc Nurs ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38456911

RESUMO

BACKGROUND: Lifelong hypertension highlights the importance of dyadic engagement in coping with the disease. Although dyadic coping is heterogeneous in patients with other diseases, little is known about it in elderly patients with hypertension. In addition, whether impaired dyadic coping is associated with frailty has yet to be elucidated. OBJECTIVES: The aim of this study was to investigate the latent profiles and characteristics of dyadic coping and the potential association between impaired dyadic coping and frailty in elderly patients with hypertension. METHODS: We recruited a total of 741 elderly patients with hypertension. Latent profile analysis was then used to identify the best-fitting model. Then, we used regression analysis to determine profile predictors and identify the association between impaired dyadic coping and frailty. RESULTS: The 5-profile model was considered to be the best-fitting model, as follows: profile 1, severely impaired dyadic coping; profile 2, mildly impaired dyadic coping; profile 3, normal dyadic coping; profile 4, better dyadic coping; and profile 5, the highest dyadic coping. In the fully adjusted model, the probability of frailty was 1.94-fold higher in the mildly impaired dyadic coping group (odds ratio, 1.94; 95% confidence interval, 1.09-3.47) and 2.66-fold higher in the severely impaired dyadic coping group (odds ratio, 2.66; 95% confidence interval, 1.11-6.39). CONCLUSIONS: We identified heterogeneity in dyadic coping and demonstrated that impaired dyadic coping was associated with frailty. Those at risk of dyadic coping impairment need to be identified early, followed by dyadic coping-based interventions to prevent or delay frailty.

10.
J Autoimmun ; 145: 103205, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493673

RESUMO

Peptide ALW (ALWPPNLHAWVP) targeting anti-dsDNA antibodies has shown promising therapeutic effects in alleviating lupus nephritis, but is potentially limited by poor stability and non-kidney targeting. We recently developed a D-form modified ALW, called D-ALW, which has the capacity to widely inhibit pathogenic polyclonal anti-dsDNA antibody reactions. Further modification of D-ALW using PEG-PLGA nanoparticles to enhance good kidney-targeting ability and extend half-life. Here, we demonstrate that the D-form modified ALW maintains higher binding and inhibition efficiencies and achieves higher stability. Most importantly, D-ALW nanoparticles exhibit excellent kidney-targeting ability and prolong the half-life of the peptides in BALB/c mice. Additionally, compared to D-ALW, D-ALW nanoparticles significantly reduce the glomerular deposition of IgG and C3, improve renal histopathologies, such as glomerular proliferation and inflammatory cells infiltration, and markedly prolong lifespan in MRL/lpr lupus-prone mice. Overall, these results establish that the D-ALW nanoparticles offer synergistic benefits in both safety and efficacy, providing long-term renal preservation and treatment advantages in lupus nephritis.

11.
Nutrients ; 16(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38474877

RESUMO

In this study, the roles of kiwifruit soluble/insoluble dietary fiber (SDF/IDF, respectively) in the pasting characteristics and in vitro digestibility of wheat starch were explored. According to RVA and rheological tests, the IDF enhanced the wheat starch viscosity, decreased the gelatinization degree of the starch granules, and exacerbated starch retrogradation. The addition of SDF in high quantities could reduce the starch gelatinization level, lower the system viscosity, and exacerbate starch retrogradation. Through determining the leached amylose content and conducing scanning electron microscopy, the IDF and SDF added in high quantities was combined with the leached amylose wrapped around the starch granules, which reduced the leached amylose content and decreased the gelatinization degree of the starch granules. The Fourier transform infrared results showed that the addition of both the IDF and SDF resulted in an enhancement in hydrogen bonding formed by the hydroxyl groups of the system. The in vitro digestion results strongly suggested that both the IDF and SDF reduced the wheat starch digestibility. The above findings are instructive for the application of both IDF and SDF in starchy functional foods.


Assuntos
Amilose , Amido , Triticum , Fibras na Dieta , Viscosidade
12.
Geriatr Nurs ; 57: 45-50, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38520817

RESUMO

This study investigates the mediating role of activity restriction in the relationship between the fear of falling and health outcomes. This was a cross-sectional study with convenience sampling of 316 nursing home residents. Generalized structural equation modeling was conducted to test the mediating role. The results showed that residents with fear of falling were more likely to restrict their activities and residents who often or always restricted activities reported lower levels of quality of life and higher levels of depression. Severe activity restriction accounted for 75 % of the total effect of fear of falling on quality of life and 69 % of the total effect of fear of falling on depression. Fall prevention efforts should focus on strategies or interventions to reduce residents' excessive fear of falling and promote activity engagement. Physical and social activities will not only prevent future falls but also improve residents' quality of life and mental health.

13.
Artif Intell Med ; 150: 102837, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38553151

RESUMO

The thickness of the choroid is considered to be an important indicator of clinical diagnosis. Therefore, accurate choroid segmentation in retinal OCT images is crucial for monitoring various ophthalmic diseases. However, this is still challenging due to the blurry boundaries and interference from other lesions. To address these issues, we propose a novel prior-guided and knowledge diffusive network (PGKD-Net) to fully utilize retinal structural information to highlight choroidal region features and boost segmentation performance. Specifically, it is composed of two parts: a Prior-mask Guided Network (PG-Net) for coarse segmentation and a Knowledge Diffusive Network (KD-Net) for fine segmentation. In addition, we design two novel feature enhancement modules, Multi-Scale Context Aggregation (MSCA) and Multi-Level Feature Fusion (MLFF). The MSCA module captures the long-distance dependencies between features from different receptive fields and improves the model's ability to learn global context. The MLFF module integrates the cascaded context knowledge learned from PG-Net to benefit fine-level segmentation. Comprehensive experiments are conducted to evaluate the performance of the proposed PGKD-Net. Experimental results show that our proposed method achieves superior segmentation accuracy over other state-of-the-art methods. Our code is made up publicly available at: https://github.com/yzh-hdu/choroid-segmentation.


Assuntos
Corioide , Aprendizagem , Corioide/diagnóstico por imagem , Retina/diagnóstico por imagem , Processamento de Imagem Assistida por Computador
14.
Phytochemistry ; 222: 114068, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38554895

RESUMO

Seven undescribed polyoxygenated ursane-type triterpenoids (vitnegundins A-G), three undescribed triterpenoid saponins (vitnegundins H-J), and 17 known ones were isolated from an EtOH extract of the aerial parts of Vitex negundo L. The structures of the undescribed compounds were established by extensive spectroscopic analysis. The absolute configurations of vitnegundins A, B, and E were determined by single-crystal X-ray diffraction data. Vitnegundins B-D are pentacyclic triterpenoids possessing rare cis-fused C/D rings and vitnegundins C-H represent undescribed ursane-type triterpenoids with 12,19-epoxy moiety. In the biological activity assay, vitnegundin A, vitnegundin E, and swinhoeic acid displayed inhibitory effects against LPS-induced NO release in BV-2 microglial cells, with IC50 values of 11.8, 44.2, and 19.6 µM, respectively.

15.
Heliyon ; 10(6): e27523, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38510040

RESUMO

Fast and precise identification of microorganisms in the early diagnosis of sepsis is crucial for enhancing patient outcomes. Digital PCR (dPCR) is a highly sensitive approach for absolute quantification that can be utilized as a culture-independent molecular technique for diagnosing sepsis pathogens. We performed a retrospective investigation on 69 ICU patients suspected of sepsis. Our findings showed that a multiplex dPCR diagnostic kit outperformed blood culture in detecting the 15 most frequent bacteria that cause sepsis. Ninety-two bacterial strains were identified using dPCR at concentrations varying from 34 copies/mL to 105,800 copies/mL. The detection rate of dPCR was much greater than that of BC, with 27.53% (19/69) versus 73.91% (51/69). The sensitivity of dPCR was 63.2%. Our research indicated that dPCR outperforms blood culture in the early detection of sepsis-causing microorganisms. The diagnostic kit can detect a greater variety of pathogens with quantitative data, including polymicrobial infections, and has a quicker processing time. DPCR is a valuable technique that could aid in the proper management of sepsis.

16.
Front Oncol ; 14: 1367200, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529383

RESUMO

Background: Controversy surrounds the efficacy of adjuvant chemotherapy (ACT) in the treatment of stage I lung adenocarcinoma (LUAD). The objective of this study was to examine the impact of the maximum standardized uptake value (SUVmax) as measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) on the efficacy of ACT in patients diagnosed with stage I LUAD. Methods: We scrutinized the medical records of 928 consecutive patients who underwent complete surgical resection for pathological stage I LUAD at our institution. The ideal cut-off value for primary tumor SUVmax in terms of disease-free survival (DFS) and overall survival (OS) was determined using the X-tile software. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results: Based on the SUVmax algorithm, the ideal cutoff values were determined to be 4.9 for DFS and 5.0 for OS. We selected 5.0 as the threshold because OS is the more widely accepted predictive endpoint. In a multivariate Cox regression analysis, SUVmax ≥ 5.0, problematic IB stage, and sublobectomy were identified as independent risk factors for poor DFS and OS. It is noteworthy that patients who were administered ACT had significantly longer DFS and OS than what was observed in the subgroup of patients with pathological stage IB LUAD and SUVmax ≥ 5.0 (p < 0.035 and p ≤ 0.046, respectively). However, there was no observed survival advantage for patients in stages IA or IB who had an SUVmax < 5.0. Conclusion: The preoperative SUVmax of tumors served as an indicator of the impact of ACT in the context of completely resected pathological stage I LUAD. Notably, patients within the Stage IB category exhibiting elevated SUVmax levels emerged as a subgroup experiencing substantial benefits from postoperative ACT.

17.
J Imaging Inform Med ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441699

RESUMO

Image registration is a fundamental task in various applications of medical image analysis and plays a crucial role in auxiliary diagnosis, treatment, and surgical navigation. However, cardiac image registration is challenging due to the large non-rigid deformation of the heart and the complex anatomical structure. To address this challenge, this paper proposes an independently trained multi-scale registration network based on an image pyramid. By down-sampling the original input image multiple times, we can construct image pyramid pairs, and design a multi-scale registration network using image pyramid pairs of different resolutions as the training set. Using image pairs of different resolutions, train each registration network independently to extract image features from the image pairs at different resolutions. During the testing stage, the large deformation registration is decomposed into a multi-scale registration process. The deformation fields of different resolutions are fused by a step-by-step deformation method, thereby addressing the challenge of directly handling large deformations. Experiments were conducted on the open cardiac dataset ACDC (Automated Cardiac Diagnosis Challenge); the proposed method achieved an average Dice score of 0.828 in the experimental results. Through comparative experiments, it has been demonstrated that the proposed method effectively addressed the challenge of heart image registration and achieved superior registration results for cardiac images.

18.
Phytomedicine ; 128: 155455, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38513376

RESUMO

BACKGROUND: Ischemic stroke (IS) is a serious cerebrovascular disease characterized by significantly elevated mortality and disability rates, and the treatments available for this disease are limited. Neuroinflammation and oxidative stress are deemed the major causes of cerebral ischemic injury. N-Cinnamoylpyrrole alkaloids form a small group of natural products from the genus Piper and have not been extensively analyzed pharmacologically. Thus, identifying the effect and mechanism of N-cinnamoylpyrrole-derived alkaloids on IS is worthwhile. PURPOSE: The present research aimed to explore the antineuroinflammatory and antioxidative stress effects of N-cinnamoylpyrrole-derived alkaloids isolated from the genus Piper and to explain the effects and mechanism on IS. METHODS: N-cinnamoylpyrrole-derived alkaloids were isolated from Piper boehmeriaefolium var. tonkinense and Piper sarmentosum and identified by various chromatographic methods. Lipopolysaccharide (LPS)-induced BV-2 microglia and a mouse model intracerebroventricularly injected with LPS were used to evaluate the antineuroinflammatory and antioxidative stress effects. Oxygen‒glucose deprivation/reperfusion (OGD/R) and transient middle cerebral artery occlusion (tMCAO) models were used to evaluate the effect of PB-1 on IS. To elucidate the fundamental mechanism, the functional target of PB-1 was identified by affinity-based protein profiling (ABPP) strategy and verified by cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS), and circular dichroism (CD) analyses. The effect of PB-1 on the NF-κB and NRF2 signaling pathways was subsequently evaluated via western blotting and immunofluorescence staining. RESULTS: The results showed that N-cinnamoylpyrrole-derived alkaloids significantly affected neuroinflammation and oxidative stress. The representative compound, PB-1 not only inhibited neuroinflammation and oxidative stress induced by LPS or OGD/R insult, but also alleviated cerebral ischemic injury induced by tMCAO. Further molecular mechanism research found that PB-1 promoted antineuroinflammatory and antioxidative stress activities via the NF-κB and NRF2 signaling pathways by targeting eEF1A1. CONCLUSION: Our research initially unveiled that the therapeutic impact of PB-1 on cerebral ischemic injury might rely on its ability to target eEF1A1, leading to antineuroinflammatory and antioxidative stress effects. The novel discovery highlights eEF1A1 as a potential target for IS treatment and shows that PB-1, as a lead compound that targets eEF1A1, may be a promising therapeutic agent for IS.

19.
J Dermatol Sci ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38514279

RESUMO

BACKGROUND: Keratinocyte dysdifferentiation and proinflammatory cytokine production play a central role in psoriatic inflammation. According to recent studies, the Rh family C glycoprotein (RHCG) enhances cell proliferation and disrupts cell differentiation. However, the specific role of RHCG psoriasis development remains unclear. OBJECTIVE: We here explored the effect of RHCG on keratinocytes under psoriatic inflammation. METHODS: The cell counting kit­8 assay was conducted to assess proliferation. RHCG protein expression was assessed through western blotting and enzyme-linked immunosorbent assays. The expression of proinflammatory cytokines and differentiation markers was analyzed through a quantitative reverse-transcription polymerase chain reaction. METHODS: The cell counting kit­8 assay was conducted to assess proliferation. RHCG protein expression was assessed through western blotting and enzyme-linked immunosorbent assays. The expression of proinflammatory cytokines and differentiation markers was analyzed through a quantitative reverse-transcription polymerase chain reaction. RESULTS: Both RHCG mRNA and protein levels increased in psoriatic skin. Notably, cultured keratinocytes treated with an M5 cocktail, which mimics psoriatic inflammation, exhibited higher RHCG expression. Furthermore, RHCG overexpression promoted keratinocyte proliferation, accompanied by an increase in the production of interleukin (IL)-1ß, IL-6, and IL-8, and tumor necrosis factor-α. RHCG overexpression also resulted in higher expression of keratin 17, a differentiation marker. Conversely, RHCG gene knockdown reduced keratinocyte proliferation and cytokine secretion. RHCG inhibition in cells recovered both keratin 1 and loricrin expression. Additionally, RHCG overexpression facilitated the phosphorylation of nuclear factor-kappa B and extracellular signal-regulated protein kinase signaling pathways. Importantly, when these signaling pathways were inhibited, the effect of RHCG on keratinocytes was attenuated. CONCLUSION: These findings support the substantial role of RHCG in psoriatic inflammation development and suggest that RHCG serves as a potential target for psoriasis treatment.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38507650

RESUMO

AIMS: This study aimed to uncover hidden patterns and predictors of symptom multi-trajectories within 30 days after discharge in patients with heart failure and assess the risk of unplanned 30-day hospital readmission in different patterns. METHODS AND RESULTS: The study was conducted from September 2022 to September 2023 in four third-class hospitals in Tianjin, China. A total of 301 patients with heart failure were enrolled in the cohort, and 248 patients completed a 30-day follow-up after discharge. Three multi-trajectory groups were identified: mild symptom status (24.19%), moderate symptom status (57.26%), and severe symptom status (18.55%). With the mild symptom status group as a reference, physical frailty, psychological frailty, and comorbid renal dysfunction were predictors of the moderate symptom status group. Physical frailty, psychological frailty, resilience, taking diuretics, and comorbid renal dysfunction were predictors of the severe symptom status group. Compared with the mild symptom status group, the severe symptom status group was significantly associated with high unplanned 30-day hospital readmission risks. CONCLUSIONS: This study identified three distinct multi-trajectory groups among patients with heart failure within 30 days after discharge. The severe symptom status group was associated with a significantly increased risk of unplanned 30-day hospital readmission. Common and different factors predicted different symptom multi-trajectories. Healthcare providers should assess the physical and psychological frailty and renal dysfunction of patients with heart failure before discharge. Inpatient care aimed at alleviating physical and psychological frailty and enhancing resilience may be important to improve patients' symptom development post-discharge.

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