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1.
Commun Biol ; 7(1): 1099, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39244596

RESUMO

Centromere pairing is crucial for synapsis in meiosis. This study delves into the Skp1-Cullin1-F-box protein (SCF) E3 ubiquitin ligase complex, specifically focusing on F-box protein 47 (FBXO47), in mouse meiosis. Here, we revealed that FBXO47 is localized at the centromere and it regulates centromere pairing cooperatively with SKP1 to ensure proper synapsis in pachynema. The absence of FBXO47 causes defective centromeres, resulting in incomplete centromere pairing, which leads to corruption of SC at centromeric ends and along chromosome axes, triggering premature dissociation of chromosomes and pachytene arrest. FBXO47 deficient pachytene spermatocytes exhibited drastically reduced SKP1 expression at centromeres and chromosomes. Additionally, FBXO47 stabilizes SKP1 by down-regulating its ubiquitination in HEK293T cells. In essence, we propose that FBXO47 collaborates with SKP1 to facilitate centromeric SCF formation in spermatocytes. In summary, we posit that the centromeric SCF E3 ligase complex regulates centromere pairing for pachynema progression in mice.


Assuntos
Centrômero , Pareamento Cromossômico , Proteínas F-Box , Espermatócitos , Animais , Masculino , Centrômero/metabolismo , Centrômero/genética , Camundongos , Espermatócitos/metabolismo , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Humanos , Células HEK293 , Proteínas Ligases SKP Culina F-Box/metabolismo , Proteínas Ligases SKP Culina F-Box/genética , Meiose , Camundongos Knockout , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Camundongos Endogâmicos C57BL
2.
Behav Neurol ; 2024: 5698119, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39233848

RESUMO

Objective: The objective of the study is to investigate whether quercetin ameliorates Alzheimer's disease (AD)-like pathology in APP/PS1 double transgenic mice and its hypothesized mechanism, contributing to the comprehension of AD pathogenesis. Methods: A total of 30 APP/PS1 transgenic mice were randomized into model group (APP/PS1), quercetin group (APP/PS1+Q), and donepezil hydrochloride group (APP/PS1+DON). Simultaneously, there were 10 C57 mice of the same age served as a control group. Three months posttreatment, the effects of quercetin on AD mice were evaluated using the Morris water maze (MWM) test, Y maze experiment, immunohistochemistry, immunofluorescence, and western blotting. Results: Results from the water maze and Y maze indicated that quercetin significantly improved cognitive impairment in APP/PS1 transgenic AD mice. Additionally, serum enzyme-linked immunosorbent assay (ELISA) results demonstrated that quercetin elevated MDA, superoxide dismutase (SOD), CAT, GSH, acetylcholine (ACh), and acetylcholinesterase (AChE) levels in AD mice. Hematoxylin-eosin (HE) staining, Nissl staining, and hippocampal tissue thioflavine staining revealed that quercetin reduced neuronal damage and Aß protein accumulation in AD mice. Western blot validated protein expression in the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/HO-1 pathway associated with oxidative stress and apoptosis, confirming quercetin's potential molecular mechanism of enhancing AD mouse cognition. Furthermore, western blot findings indicate that quercetin significantly alters protein expression in the Keap1/Nrf2/HO-1 pathway. Moreover, molecular docking analysis suggests that Keap1, NQO1, HO-1, caspase-3, Bcl-2, and Bax proteins in the Keap1/Nrf2/HO-1 pathway may be potential regulatory targets of quercetin. These findings will provide a molecular basis for quercetin's clinical application in AD treatment. Conclusion: Quercetin can improve cognitive impairment and AD-like pathology in APP/PS1 double transgenic mice, potentially related to quercetin's activation of the Keap1/Nrf2/HO-1 pathway and reduction of cell apoptosis.


Assuntos
Doença de Alzheimer , Precursor de Proteína beta-Amiloide , Apoptose , Encéfalo , Disfunção Cognitiva , Modelos Animais de Doenças , Heme Oxigenase-1 , Proteína 1 Associada a ECH Semelhante a Kelch , Camundongos Transgênicos , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Quercetina , Animais , Quercetina/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Heme Oxigenase-1/metabolismo , Apoptose/efeitos dos fármacos , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Transdução de Sinais/efeitos dos fármacos , Presenilina-1/genética , Presenilina-1/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Antioxidantes/farmacologia , Antioxidantes/metabolismo
3.
Artigo em Inglês | MEDLINE | ID: mdl-39278576

RESUMO

BACKGROUND: Right ventricular (RV) involvement has been reported in type 2 diabetes mellitus (T2DM). The relationship between glycemic control and RV function remains unknown. We aimed to investigate the association between glycemic control and RV function assessed by two-dimensional speckle-tracking echocardiography (2D-STE) and three-dimensional echocardiography (3DE) in T2DM individuals. METHODS: This study prospectively enrolled 207 patients with T2DM and 84 individuals with normal glucose metabolism (NGM). T2DM patients were divided into two subgroups according to glycated hemoglobin (HbA1c) level: controlled (HbA1c < 7.0%, n = 91) and uncontrolled subgroup (HbA1c ≥ 7.0%, n = 116). RV free wall longitudinal strain (RVFWLS) was acquired by 2D-STE, RV volumes and RV ejection fraction (RVEF) were assessed using 3DE. RV coupling to pulmonary circulation was defined as the ratio of RVFWLS/pulmonary artery systolic pressure (PASP). RESULTS: Controlled and uncontrolled T2DM subgroups had impaired RV function as reflected by reduced RVFWLS and RVEF compared to the NGM group. The reduction in RVFWLS was more pronounced in the uncontrolled subgroup than in the controlled subgroup (P < 0.001), whereas no significant difference was found in RVEF between these two T2DM subgroups. Higher PASP and lower RVFWLS/PASP ratio were also noted in uncontrolled T2DM patients. Additionally, the incidence of RV dysfunction was significantly higher in the uncontrolled T2DM patients than in the controlled subgroup (43.1% vs 17.6%, P < 0.001). After adjustment for potential clinical confounders, PASP and left ventricular parameters, HbA1c level was independently associated with RVFWLS (ß = 0.290, P = 0.003) and RVFWLS/PASP ratio (ß = 0.028, P = 0.006). CONCLUSIONS: Subclinical RV myocardial dysfunction is present in T2DM patients and is more pronounced in patients with uncontrolled blood glucose. HbA1c level is independently associated with subclinical RV myocardial dysfunction, providing further insight into a possible link between poor glycemic control and diabetic cardiomyopathy.

4.
Front Oncol ; 14: 1387014, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39309738

RESUMO

Background: Primary malignant melanoma (MM) of skin threatens health, especially in the older population, causing a significant risk of early death. The purpose of this study was to establish a diagnostic nomogram to predict the early mortality risk in older patients with primary skin MM and to determine the independent risk factors of cancer-specific early death in such patients. Methods: The Surveillance, Epidemiology and End Results (SEER) database provided the clinical and pathological characteristics of older patients with primary skin MM from 2000 to 2019. Initially, a 7:3 random assignment was used to place the recruited patients into training and validation cohorts. Then, the independent risk variables of cancer-specific early death in those individuals were determined using univariate and multivariate logistic regression analysis. Those patients' diagnostic nomograms were constructed using the acquired independent risk variables. Ultimately, the performance of the newly created diagnostic nomogram was verified using calibration curves, receiver operating characteristic (ROC), and decision curve analysis (DCA) curves. Results: In this study, 2,615 patients in total were included. Age, histology, liver metastasis, tumor stage, surgery, therapy, and radiation were found to be independent risk factors following statistical analysis, with a special emphasis on early death in older patients with primary skin MM. A diagnostic nomogram for the cancer-specific early death risk was created and validated based on these variables. High agreement was reported between the expected and actual probabilities in the calibration curves. Area under the curves (AUC) of the novel created diagnostic nomogram was greater than that of each independent risk factor, with AUCs for the training and validation cohorts being 0.966 and 0.971, respectively. The nomogram had a high value for its applicability in clinical settings, according to DCA. Conclusion: In older patients with primary skin MM, the current study created a diagnostic nomogram to predict the probability of cancer-specific early death. Because of the nomograms' good performance, physicians will be better able to identify older patients who are at a high risk of early death and treat them individually to increase their survival benefit.

5.
Front Cardiovasc Med ; 11: 1405754, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39175629

RESUMO

Purpose: The impact of aortic stenosis (AS) severity on multidirectional myocardial function in patients with bicuspid aortic valve (BAV) remains unclear, despite the recognized presence of early left ventricular longitudinal myocardial dysfunction in BAV patients with normal valve function. The aim of the study was to evaluate the multidirectional myocardial functions of BAV patients. Methods: A total of 86 BAV patients (age 46.71 ± 13.62 years, 69.4% men) with normally functioning (BAV-nf), mild AS, moderate AS, and severe AS with preserved left ventricular ejection fraction (LVEF ≥ 52%) were included. 30 healthy volunteers were recruited as the control group. Multidirectional strain and volume analysis were performed by three-dimensional speckle tracking echocardiography(3D-STE). Results: Global longitudinal strain (GLS), and global radial strain (GRS) were reduced in BAV-nf patients compared with the controls. With each categorical of AS severity from BAV-nf to severe AS, there was an associated progressive impairment of GLS and GRS (all P < 0.001). Global circumferential strain (GCS) did not show a significant decrease from BAV-nf to mild AS but began to decrease from moderate AS. Multiple linear regressions indicated that indexed aortic valve area (AVA/BSA), as a measure of AS severity, was an independent determinant of GLS, GCS and GRS. Conclusions: Left ventricular longitudinal myocardial reduction is observed even in patients with well-functioning bicuspid aortic valves. With each categorical increase in the grade of AS severity from normally functioning to severe aortic stenosis, there was an associated progressive impairment of longitudinal myocardial function. Furthermore, circumferential myocardial function was starting damaged from moderate AS. AVA/BSA was independently associated with multidirectional myocardial function injuries.

6.
Sci Total Environ ; 950: 175228, 2024 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-39102954

RESUMO

Soil freeze-thaw cycles (FTCs) are common in temperate agricultural ecosystems during the non-growing season and are progressively influenced by climate change. The impact of these cycles on soil microbial communities, crucial for ecosystem functioning, varies under different agricultural management practices. Here, we investigated the dynamic changes in soil microbial communities in a Mollisol during seasonal FTCs and examined the effects of stover mulching and nitrogen fertilization. We revealed distinct responses between bacterial and fungal communities. The dominant bacterial phyla reacted differently to FTCs: for example, Proteobacteria responded opportunistically, Actinobacteria, Acidobacteria, Choroflexi and Gemmatimonadetes responded sensitively, and Saccharibacteria exhibited a tolerance response. In contrast, the fungal community composition remained relatively stable during FTCs, except for a decline in Glomeromycota. Certain bacterial OTUs acted as sensitive indicators of FTCs, forming keystone modules in the network that are closely linked to soil carbon, nitrogen content and potential functions. Additionally, neither stover mulching nor nitrogen fertilization significantly influenced microbial richness, diversity and potential functions. However, over time, more indicator species specific to these agricultural practices began to emerge within the networks and gradually occupied the central positions. Furthermore, our findings suggest that farming practices, by introducing keystone microbes and changing interspecies interactions (even without changing microbial richness and diversity), can enhance microbial community stability against FTC disturbances. Specifically, higher nitrogen input with stover removal promotes fungal stability during soil freezing, while lower nitrogen levels increase bacterial stability during soil thawing. Considering the fungal tolerance to FTCs, we recommend reducing nitrogen input for manipulating bacterial interactions, thereby enhancing overall microbial resilience to seasonal FTCs. In summary, our research reveals that microbial responses to seasonal FTCs are reshaped through land management to support ecosystem functions under environmental stress amid climate change.


Assuntos
Agricultura , Mudança Climática , Congelamento , Microbiota , Estações do Ano , Microbiologia do Solo , Solo , Agricultura/métodos , Solo/química , Bactérias , Ecossistema , Fungos , Nitrogênio/análise
7.
J Int Adv Otol ; 20(3): 261-271, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-39158520

RESUMO

This article evaluated the current status and focus areas in benign paroxysmal positional vertigo (BPPV) research in the world and to predict the direction of future research. Web of Science Core Collection were searched from January 1, 2002, to December 31, 2021. Bibliometric and statistical analysis were conducted to generate the basic information of the publications. A total of 1255 publications were identified, with an increasing trend in the number of annual number of publications from 2019 to 2021. Otology & Neurotology was the most productive journal. Kim J, Kim C, and Lee J from South Korea were the top 3 productive authors. Seoul National University is the most influential institution. The top 5 cited burst keywords include recurrence, osteoporosis, bone mineral density, vitamin D deficiency, and BPPV. The annual number of publications would continue to grow. The future research of BPPV will concentrate on osteoporosis and recurrence.


Assuntos
Vertigem Posicional Paroxística Benigna , Bibliometria , Vertigem Posicional Paroxística Benigna/diagnóstico , Humanos , Osteoporose , República da Coreia/epidemiologia , Recidiva , Deficiência de Vitamina D/epidemiologia
8.
Front Cardiovasc Med ; 11: 1417757, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39161660

RESUMO

Background and aims: Transcatheter tricuspid valve replacement (TTVR) has recently emerged as a novel therapeutic approach for managing severe tricuspid regurgitation (TR). However, surgical tricuspid valve replacement (STVR) continues to be the predominant treatment modality. There are limited comparative data on both procedures. This study aimed to compare clinical and echocardiographic outcomes between patients who underwent mini-thoracotomy transatrial LuX-Valve TTVR and those who underwent STVR. Methods: This study prospectively collected patients with severe TR who underwent TTVR (n = 29) or isolated STVR (n = 59) at Wuhan Union Hospital from 2019 to 2022. All TTVR patients received the LuX-Valve via a mini-thoracotomy and transatrial approach. The clinical and echocardiographic outcomes were compared at 30-day and one-year follow-ups. Results: At baseline, patients with LuX-Valve TTVR had higher surgical risk scores and a greater proportion of right ventricular dysfunction compared with STVR. In the early postoperative period, the STVR group had a greater decrease in right ventricular function. Hospital length of stay (LOS), intensive care unit LOS, total procedure time, and tracheal intubation time were shorter in the TTVR than in the STVR group. The incidence of postoperative paravalvular leaks was higher among patients who underwent TTVR. Compared to the STVR group, the pacemaker implantation rate was lower in the TTVR group. During follow-up, the peak tricuspid valve velocity and mean gradient in the TTVR group were consistently lower than those in the STVR group. There was similar mortality between TTVR and STVR at 30-day and one-year follow-ups. Conclusions: The mini-thoracotomy transatria LuX-Valve TTVR has a higher incidence of paravalvular leaks and a lower rate of pacemaker implantation than STVR, with similar 30-day and one-year mortality rates. In some respects, mini-thoracotomy transatrial LuX-Valve TTVR may be a feasible and safe treatment option for specific populations, or it could potentially serve as an alternative therapy to supplement conventional STVR. Further follow-up is required to assess differences in long-term clinical outcomes and valve durability.

9.
J Am Chem Soc ; 146(35): 24377-24388, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39163211

RESUMO

Chiral hybrid organic-inorganic metal halides are highly promising chiroptoelectronic materials with potential applications in several fields, such as circularly polarized photodetectors, second-order nonlinear optics, and spin-selective devices. However, the ability of manipulating the chiroptical response and the chirality transfer from the organic ligands require one to shed light on structure-property correlations. Herein, we devised and prepared two novel Ge-based chiral hybrid organic-inorganic metal halides showing a different structural topology, namely, a 1D and a 2D arrangement, but composed of the same chemical building blocks: (R/S-ClMBA)3GeI5 and (R/S-ClMBA)2GeI4. Through a combined experimental and computational investigation on these samples, we discuss the impact of structural dimensionality on chiroptical properties, chirality transfer, and spin-splitting effects; also, we highlight the impact of structural distortions. The approach presented here paves the way for a solid understanding of the factors affecting the properties of chiral metal halides, thus allowing a future wise materials engineering.

11.
Int J Nurs Stud ; 159: 104849, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39146609

RESUMO

BACKGROUND: Comprehensive geriatric assessment (CGA) is performed by a multidisciplinary team and includes systematic comprehensive team assessment and treatment. Comprehensive geriatric assessment has become a fundamental component of geriatric nursing, as a multidimensional approach is necessary to achieve the best diagnosis and therapy for older adults with frailty. OBJECTIVE: The aim of our review was to analyze the effects of comprehensive geriatric assessment interventions on older adults with frailty in hospital settings. METHODS: The PubMed, Web of Science, Embase, CINAHL and Cochrane Library databases were systematically searched from inception to February 28, 2024. Only randomized controlled trials were included in the analysis. The risk ratios (RRs) or standardized mean differences (SMDs) were calculated to determine the pooled intervention effects. Sensitivity analyses and publication bias analyses were also conducted. Methodological quality and evidence were assessed using the RoB2 tool and GRADE pro online tool. RESULTS: A total of 18 randomized controlled trials were included in this review. The results showed that participants in the intervention group had a lower risk of having decreased activities of daily living than did those in the control group (RR = 0.55, 95 % CI: 0.33 to 0.92, P = 0.021, low certainty evidence). Comprehensive geriatric assessment was associated with a reduced mortality risk (RR = 0.85, 95 % CI: 0.73 to 0.99, P = 0.038, high certainty evidence). CONCLUSION: In conclusion, this systematic review analyzed the available literature, and the results showed that comprehensive geriatric assessment had significant benefits in terms of increased independence and was associated with a reduced mortality risk for older adults with frailty in hospital settings. However, the evidence was limited. Thus, more research is needed in the future to further enrich the evidence in the field of comprehensive geriatric assessment interventions for older adults with frailty.


Assuntos
Avaliação Geriátrica , Humanos , Idoso , Avaliação Geriátrica/métodos , Fragilidade/diagnóstico , Idoso Fragilizado
12.
Ageing Res Rev ; 100: 102449, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39111408

RESUMO

BACKGROUND: Globally, there is an increase in the number of older people living with frailty, thus effective strategies to prevent and manage frailty are of paramount importance. The effects of nurse-led interventions on the physical and mental health of (pre) frail people have not yet been systematically reviewed. METHODS: We searched the PubMed, Web of Science, EMBASE, CINAHL, and the Cochrane Library from inception to 8 May 2024. Eligible studies included randomized controlled trials and quasi-experimental trials reporting the effects of nurse-led interventions on physical and mental health outcomes among (pre) frail people. Two researchers independently extracted trial data and assessed the risk of bias by using the risk of bias tool recommended by the Cochrane Back Review Group and the Methodological Index for Non-Randomized Studies. RESULTS: 14 randomized controlled trials and 6 quasi-experimental studies, encompassing 3943 participants, were included in the review. Nurse-led interventions included function-based care (cognitive behavioral therapy, exercise, and multi-domain intervention), personalized integrated care, and advance care planning. The reported outcomes were multiple with most results showing inconsistencies. Overall, function-based care showed more positive effects on physical outcomes (31/37, 84 %) and mental health (11/12, 92 %). However, the effectiveness of existing personalized integrated care and advance care planning might be limited. CONCLUSIONS: Nurse-led interventions may effectively improve both physical and mental health among (pre) frail older adults, although effectiveness varies by intervention type. Nurses have the potential to play a leading role, both individually and within multidisciplinary teams, in alleviating the rising global burden of frailty. We need more well-designed randomized controlled trials to confirm the effectiveness of nurse-led interventions and identify the most effective type of interventions.


Assuntos
Idoso Fragilizado , Fragilidade , Saúde Mental , Idoso , Idoso de 80 Anos ou mais , Humanos , Idoso Fragilizado/psicologia , Fragilidade/enfermagem , Fragilidade/psicologia
13.
Curr Med Sci ; 44(4): 854-863, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39112916

RESUMO

OBJECTIVE: This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide (LPS) and to examine the effects of astragaloside IV on key targets using high-throughput sequence technology and bioinformatics analyses. METHODS: PC12 cells in the logarithmic growth phase were treated with LPS at final concentrations of 0.25, 0.5, 0.75, 1, and 1.25 mg/mL for 24 h. Cell morphology was evaluated, and cell survival rates were calculated. A neurocyte inflammatory model was established with LPS treatment, which reached a 50% cell survival rate. PC12 cells were treated with 0.01, 0.1, 1, 10, or 100 µmol/L astragaloside IV for 24 h. The concentration of astragaloside IV that did not affect the cell survival rate was selected as the treatment group for subsequent experiments. NOS activity was detected by colorimetry; the expression levels of ERCC2, XRCC4, XRCC2, TNF-α, IL-1ß, TLR4, NOS and COX-2 mRNA and protein were detected by RT-qPCR and Western blotting. The differentially expressed genes (DEGs) between the groups were screened using a second-generation sequence (fold change>2, P<0.05) with the following KEGG enrichment analysis, RT-qPCR and Western blotting were used to detect the mRNA and protein expression of DEGs related to the IL-17 pathway in different groups of PC12 cells. RESULTS: The viability of PC12 cells was not altered by treatment with 0.01, 0.1, or 1 µmol/L astragaloside IV for 24 h (P>0.05). However, after treatment with 0.5, 0.75, 1, or 1.25 mg/mL LPS for 24 h, the viability steadily decreased (P<0.01). The mRNA and protein expression levels of ERCC2, XRCC4, XRCC2, TNF-α, IL-1ß, TLR4, NOS, and COX-2 were significantly increased after PC12 cells were treated with 1 mg/mL LPS for 24 h (P<0.01); however, these changes were reversed when PC12 cells were pretreated with 0.01, 0.1, or 1 µmol/L astragaloside IV in PC12 cells and then treated with 1 mg/mL LPS for 24 h (P<0.05). Second-generation sequencing revealed that 1026 genes were upregulated, while 1287 genes were downregulated. The DEGs were associated with autophagy, TNF-α, interleukin-17, MAPK, P53, Toll-like receptor, and NOD-like receptor signaling pathways. Furthermore, PC12 cells treated with a 1 mg/mL LPS for 24 h exhibited increased mRNA and protein expression of CCL2, CCL11, CCL7, MMP3, and MMP10, which are associated with the IL-17 pathway. RT-qPCR and Western blotting analyses confirmed that the DEGs listed above corresponded to the sequence assay results. CONCLUSION: LPS can damage PC12 cells and cause inflammatory reactions in nerve cells and DNA damage. astragaloside IV plays an anti-inflammatory and DNA damage protective role and inhibits the IL-17 signaling pathway to exert a neuroprotective effect in vitro.


Assuntos
Anti-Inflamatórios , Sobrevivência Celular , Reparo do DNA , Lipopolissacarídeos , Saponinas , Triterpenos , Animais , Células PC12 , Ratos , Lipopolissacarídeos/farmacologia , Triterpenos/farmacologia , Saponinas/farmacologia , Anti-Inflamatórios/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos
15.
J Thorac Dis ; 16(5): 3117-3128, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38883679

RESUMO

Background: Left atrioventricular valvular regurgitation (LAVVR) recurrence after partial and transitional atrioventricular septal defect (AVSD) repair is the main risk factor associated with reoperation or mortality. The purpose of this study was to identify risk factors associated with the recurrence of LAVVR after surgical repair of transitional and partial AVSD at a single institution. Methods: A hundred and fifty-seven patients who underwent anatomical repair for partial and transitional AVSD from January 2013 to December 2021 were included in our institutional database. Demographic characteristics, operative information, comorbidities, complications, and outcomes were retrieved from electronic medical records. Echocardiographic evaluations included cardiac dimensions, the degree of LAVVR, and the anatomy of the atrioventricular valve. Results: After a median follow-up period of 5.8 years, 40 patients had recurrent moderate or even more severe LAVVR. Compared with patients without recurrent LAVVR, those experiencing LAVVR recurrence were more likely to have larger preoperative left atrial (LA) size and larger left ventricular (LV) size after standardization, larger left atrioventricular valve (LAVV) cleft width, higher proportions of preoperative moderate or even more severe LAVVR, and immediately postoperative mild to moderate or even more severe LAVVR. Univariate Cox regression analysis showed that age at first repair, height, LA size after standardization, LV size after standardization, the severity of preoperative LAVVR, immediately postoperative LAVVR, and the LAVV cleft width more than 1cm were risk factors for recurrent LAVVR (P<0.05 for all). Multivariable Cox regression analysis showed that mild to moderate or even more severe LAVVR postoperatively [hazard ratio (HR) 9.53, 95% confidence interval (CI): 3.78-24.01; P<0.001], the width of LAVV cleft more than 1 cm (HR: 3.90, 95% CI: 1.80-8.48; P<0.001) and age at first repair (HR: 0.45, 95% CI: 0.31-0.66; P<0.001) were independently associated with the recurrence of LAVVR. Conclusions: The width of LAVV cleft, mild to moderate or even more severe LAVVR immediately after surgery, and age at initial surgery are risk factors for recurrent LAVVR. The presence of recurrent LAVVR necessitates proactive surveillance to facilitate timely reintervention.

16.
Diagnostics (Basel) ; 14(12)2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38928685

RESUMO

As an integral part of the mitral valve apparatus, the left ventricle papillary muscle (PM) controls mitral valve closure during systole and participates in the ejection process during left ventricular systole. Mitral regurgitation (MR) is the most immediate and predominant result when the PM is structurally or functionally abnormal. However, dysfunction of the PM is easily underestimated or overlooked in clinical interventions for MR-related diseases. Therefore, adequate recognition of PM dysfunction and PM-derived MR is critical. In this review, we systematically describe the normal anatomical variations in the PM and the pathophysiology of PM dysfunction-related diseases and summarize the commonly used parameters and the advantages and disadvantages of various noninvasive imaging modalities for the structural and functional assessment of the PM.

17.
Am J Cardiovasc Drugs ; 24(4): 547-556, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38850398

RESUMO

OBJECTIVE: The clinical advantage of alprostadil [prostaglandin E1 (PGE1)] in the treatment of microcirculatory disturbances (defined as no-reflow or slow-flow) in acute percutaneous coronary intervention (PCI) is still disputed. The purpose of our study was to review the efficacy of PGE1 supplements in patients with acute myocardial infarction (AMI) who had urgent PCI. DESIGN: This study was a meta-analysis of randomized controlled trials. DATA SOURCES: PubMed, Embase, the Cochrane Library, Ovid, ProQuest, Scopus, the Chinese BioMedical Literature Database, China National Knowledge Internet, the China Science and Technology Journal Database, and the Wanfang Data Knowledge Service Platform were used as sources. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included randomized controlled trials including PGE1 for the treatment of intraoperative microcirculatory disorders and major cardiovascular adverse events in emergency PCI in people with AMI. Independent data extraction was conducted, and study quality was assessed. The meta-analysis was carried out by using random effects models to calculate the risk ratio (RR) of microcirculatory disorders between groups receiving PGE1 and those receiving placebo, nitroglycerin, or tirofiban. MAIN OUTCOME MEASURES: The primary endpoint of the study was the incidence of microcirculatory disturbances. Secondary outcomes included corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC), the percentage of patients with TIMI myocardial perfusion grade 3 (TMPG3), and the percentage of patients with myocardial blush grade 3 (MBG3) as efficacy indicators. Additionally, major adverse cardiovascular events (MACE) at 30 days and 180 days were assessed as safety indicators. RESULTS: There were 18 trials involving a total of 1458 participants. PGE1 significantly reduced the occurrence of microcirculation disorders compared with conventional medications and placebo [risk ratio 0.48, 95% confidence interval (CI) 0.36-0.63, I2 = 46%; cTFC (RR -4.74, 95% -6.85 to -2.63, I2 93%); percentage of patients with TMPG3 (RR 1.34, 95% CI 1.07-1.68, I2 70%) or MBG3 (RR 1.33, 95% CI 1.19-1.49, I2 0%); major adverse cardiovascular events (MACEs) in 30 days (RR 0.48, 95% CI 0.27-0.86, I2 0%); and MACEs in 180 days (RR 0.41, 95% CI 0.28-0.60, I2 0%)]. CONCLUSIONS: We found that PGE1 decreased the occurrence of micro-circulation disturbance in AMI and enhanced the outcome of PCI. Additional studies should be conducted to confirm these findings.


Assuntos
Alprostadil , Microcirculação , Infarto do Miocárdio , Intervenção Coronária Percutânea , Ensaios Clínicos Controlados Aleatórios como Assunto , Alprostadil/uso terapêutico , Alprostadil/efeitos adversos , Alprostadil/administração & dosagem , Humanos , Intervenção Coronária Percutânea/métodos , Intervenção Coronária Percutânea/efeitos adversos , Microcirculação/efeitos dos fármacos , Vasodilatadores/uso terapêutico , Vasodilatadores/efeitos adversos
18.
Adv Mater ; 36(30): e2400259, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38881361

RESUMO

Li-rich NMCs layered oxides, with the general formula of Li[LixNiyMnzCo1- x - y - z]O2, are known for their exceptionally high capacities but remain yet to be practicalized in the real world. They have attracted enormous research attention due to their complex structure and intriguing redox mechanisms, with a particular focus on anionic redox over the past decade. While fundamental understandings are fruitful, the practical considerations are emphasized here by providing perspectives on how Li-rich NMCs are limited by practical roadblocks and guidelines on how to cope with these limitations. It is also demonstrated that, via a techno-economic analysis, Li-rich NMCs have material cost ($/kg) highly dependent on the lithium price, but still preserve the dominance of lower pack cost ($/kWh) than other cathode candidates principally owing to their larger material energy densities. In addition to their pure application in electric-vehicle batteries, using them as "electrode additive" or "sacrificial agent" can further multiply their practicalities in assortment of scenarios, which is further discussed.

19.
Adv Sci (Weinh) ; 11(26): e2309907, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38696589

RESUMO

Myocardial ischemia/reperfusion injury (MIRI) is the leading cause of irreversible myocardial damage. A pivotal pathogenic factor is ischemia/reperfusion (I/R)-induced cardiomyocyte ferroptosis, marked by iron overload and lipid peroxidation. However, the impact of lipid droplet (LD) changes on I/R-induced cardiomyocyte ferroptosis is unclear. In this study, an aggregation-induced emission probe, TPABTBP is developed that is used for imaging dynamic changes in LD during myocardial I/R-induced ferroptosis. TPABTBP exhibits excellent LD-specificity, superior capability for monitoring lipophagy, and remarkable photostability. Molecular dynamics (MD) simulation and super-resolution fluorescence imaging demonstrate that the TPABTBP is specifically localized to the phospholipid monolayer membrane of LDs. Imaging LDs in cardiomyocytes and myocardial tissue in model mice with MIRI reveals that the LD accumulation level increase in the early reperfusion stage (0-9 h) but decrease in the late reperfusion stage (>24 h) via lipophagy. The inhibition of LD breakdown significantly reduces the lipid peroxidation level in cardiomyocytes. Furthermore, it is demonstrated that chloroquine (CQ), an FDA-approved autophagy modulator, can inhibit ferroptosis, thereby attenuating MIRI in mice. This study describes the dynamic changes in LD during myocardial ischemia injury and suggests a potential therapeutic target for early MIRI intervention.


Assuntos
Modelos Animais de Doenças , Ferroptose , Gotículas Lipídicas , Traumatismo por Reperfusão Miocárdica , Miócitos Cardíacos , Animais , Camundongos , Miócitos Cardíacos/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Gotículas Lipídicas/metabolismo , Masculino , Simulação de Dinâmica Molecular , Peroxidação de Lipídeos
20.
J Am Chem Soc ; 146(22): 15411-15419, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38780106

RESUMO

Tuning the properties of materials by using external stimuli is crucial for developing versatile smart materials. Strong coupling among the order parameters within a single-phase material constitutes a potent foundation for achieving precise property control. However, cross-coupling is fairly weak in most single materials. Leveraging first-principles calculations, we demonstrate a layered mixed anion compound MoBr2O2 that exhibits electric-field switchable spontaneous polarization and ultrastrong coupling between polar distortion and electronic structures as well as optical properties. It offers feasible avenues of achieving tunable Rashba spin-splitting, electrochromism, thermochromism, photochromism, and nonlinear optics by applying an external electric field to a single domain sample and heating, as well as intense light illumination. Additionally, it exhibits an exceptionally large photostrictive effect. These findings not only showcase the feasibility of achieving multiple order parameter coupling within a single material but also pave the way for comprehensive applications based on property control, such as energy harvesting, information processing, and ultrafast control.

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