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1.
Qual Health Res ; : 10497323241233438, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477095

RESUMO

In the context of the global COVID-19 pandemic, this study focuses on Chinese university students, employing graphic elicitation as a qualitative research method to analyze their hand-drawn paintings and related descriptions. Augmented by A/r/tography and metacognitive methods, the research aims to unveil the participants' collective memory, as well as the perspectives and responses of these students to policies related to the pandemic. By specifically examining this particular demographic, the study incorporates Fairclough's ethical theory, applying deontological ethics, consequentialist ethics, and virtue ethics to establish a comprehensive framework for evaluating adjustments to pandemic response policies. This research not only enhances our understanding of how these university students perceive and adapt to COVID-19 policies but also provides valuable insights for decision-makers. The particular methodology, combining graphic elicitation and metacognitive research, contributes to policy assessment and ethical analysis, offering a nuanced perspective on the interplay between individual perceptions, policy responses, and ethical considerations amid the complexities of a public health crisis.

2.
Small ; 19(8): e2206400, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36504297

RESUMO

The fast electrochemical kinetics behavior and long cycling life have been the goals in developing anode materials for potassium ion batteries (PIBs). On account of high electron conductivity and theoretical capacity, transition metal selenides have been deemed as one of the promising anode materials for PIBs. Herein, a systematic structural manipulation strategy, pertaining to the confine of Fe3 Se4 particles by 3D graphene and the dual phosphorus (P) doping to the Fe3 Se4 /3DG (DP-Fe3 Se4 /3DG), has been proposed to fulfill the efficient potassium-ion (K-ion) evolution kinetics and thus boost the K-ion storage performance. The theoretical calculation results demonstrate that the well-designed dual P doping interface can effectively promote K-ion adsorption behavior and provide a low energy barrier for K-ion diffusion. The insertion-conversion and adsorption mechanism for multi potassium storage behavior in DP-Fe3 Se4 /3DG composite has been also deciphered by combining the in situ/ex situ X-ray diffraction and operando Raman spectra evidences. As expected, the DP-Fe3 Se4 /3DG anode exhibits superior rate capability (120.2 mA h g-1 at 10 A g-1 ) and outstanding cycling performance (157.9 mA h g-1 after 1000 cycles at 5 A g-1 ).

3.
Small ; 19(42): e2303642, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37323120

RESUMO

Nickel sulfides with high theoretical capacity are considered as promising anode materials for sodium-ion batteries (SIBs); however, their intrinsic poor electric conductivity, large volume change during charging/discharging, and easy sulfur dissolution result in inferior electrochemical performance for sodium storage. Herein, a hierarchical hollow microsphere is assembled from heterostructured NiS/NiS2 nanoparticles confined by in situ carbon layer (H-NiS/NiS2 @C) via regulating the sulfidation temperature of the precursor Ni-MOFs. The morphology of ultrathin hollow spherical shells and confinement of in situ carbon layer to active materials provide rich channels for ion/electron transfer and alleviate the effects of volume change and agglomeration of the material. Consequently, the as-prepared H-NiS/NiS2 @C exhibit superb electrochemical properties, satisfactory initial specific capacity of 953.0 mA h g-1 at 0.1 A g-1 , excellent rate capability of 509.9 mA h g-1 at 2 A g-1 , and superior longtime cycling life with 433.4 mA h g-1 after 4500 cycles at 10 A g-1 . Density functional theory calculation shows that heterogenous interfaces with electron redistribution lead to charge transfer from NiS to NiS2 , and thus favor interfacial electron transport and reduce ion-diffusion barrier. This work provides an innovative idea for the synthesis of homologous heterostructures for high-efficiency SIB electrode materials.

4.
Anticancer Drugs ; 34(9): 971-978, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37578746

RESUMO

To evaluate the relationship between the use of proton pump inhibitors (PPI) and the risk of gastric cancer and colorectal cancer by using meta-analysis. Computer search PUBMED, EMBASE, Cochrane Library, CNKI and Wanfang database to obtain relevant literature on the use of PPI and the risk of gastric cancer and colorectal cancer, extract relevant data, and use Stata14.0 for Meta-analysis. A total of 24 articles were included, including 12 articles for gastric cancer and 12 articles for colorectal cancer. A total of 5 313 749 persons were included in the study and analysis. Meta-analysis results showed that the risk of gastric cancer in PPI users was significantly increased [risk ratio (RR) = 2.04, 95% confidence interval (CI) (1.33-2.75)], and the regional subgroup analysis results showed that in Europe [RR = 2.01, 95% CI (0.92, 3.09), P < 0.05] and Asia [RR = 2.15, 95% CI (1.16, 3.14), P < 0.05] This risk is higher, and Asia is higher than Europe. The risk of colorectal cancer is slightly increased [RR = 1. 22, 95% CI (1.03, 1.40, P < 0.05], and the regional subgroup analysis results show that in Europe [RR = 1.05 95% CI (0.98, 1.12), P < 0.05] and Asia [RR = 1.18, 95% CI (1.10, 1.27), P < 0.05]. This risk is low, but Asia is higher than Europe. The use of PPI significantly increases gastric cancer However, the risk of colorectal cancer is not significantly increased. The risk of gastric cancer and colorectal cancer in the population using PPI in Asia is higher than that in Europe.


Assuntos
Neoplasias Colorretais , Neoplasias Gástricas , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/epidemiologia , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/epidemiologia
5.
J Nucl Cardiol ; 30(3): 1166-1172, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35927377

RESUMO

BACKGROUND: The feasibility and significance of imaging pulmonary artery (PA) remodeling with 68 Ga-fibroblast activating protein inhibitor (FAPI) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) have not yet been addressed. METHODS: 68 Ga-FAPI-04 uptake in the PA and ascending artery was evaluated in 13 patients with CTEPH and 13 matched non-CTEPH controls. The correlations of PA 68 Ga-FAPI-04 uptake and remodeling parameters derived from right heart catheterization (RHC) were analyzed. RESULTS: Of the 13 patients with CTEPH, nine (69%) showed visually enhanced 68 Ga-FAPI-04 uptake, whereas none of the control subjects had increased 68 Ga-FAPI-04 uptake in the PA. The prevalence of enhanced uptake in the main, lobar, and segmental PAs was 45% (17/38), 33% (16/48), and 28% (44/159), respectively. 68 Ga-FAPI-04 activity in the PA was positively correlated with pulmonary arterial diastolic pressure (r = 0.571, P = 0.041). CONCLUSION: 68 Ga-FAPI-04 has the potential for imaging fibroblast activation in the PA wall, and 68 Ga-FAPI-04 activity in PA is positively correlated with pulmonary arterial diastolic pressure.


Assuntos
Hipertensão Pulmonar , Quinolinas , Humanos , Artéria Pulmonar , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fibroblastos
6.
Anal Bioanal Chem ; 415(7): 1305-1311, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36370201

RESUMO

Cardiomyocyte-derived extracellular vesicles (EVs) are a promising class of biomarkers that can advance the diagnosis of many kinds of cardiovascular diseases. Herein, we develop a new electrochemical method for the feasible detection of cardiomyocyte-derived EVs in biological fluids. The core design of the method is the fabrication of a peptide-anchored biomimetic interface consisting of a lipid bilayer and peptide probes. On the one hand, the lipid bilayer provides excellent antifouling ability to the electrode interface and facilitates the anchoring of peptide probes. On the other hand, the peptide probes equip the electrode interface with excellent binding capability and affinity to CD172a, a specific marker of cardiomyocyte-derived EVs, thus enabling the efficient and selective detection of target EVs. Taking EVs derived from the heart myoblast cells H9C2 as the model target, the method displays a wide linear detection range from 1 × 103 to 1 × 108 particles/mL with a desirable detection limit of 132 particles/mL. Furthermore, the method shows good performance in biological fluids such as serum, and thus may have great potential for practical use in the diagnosis of cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Vesículas Extracelulares , Humanos , Doenças Cardiovasculares/metabolismo , Miócitos Cardíacos , Biomimética , Bicamadas Lipídicas/metabolismo , Vesículas Extracelulares/metabolismo , Peptídeos/metabolismo
7.
Future Oncol ; 19(27): 1865-1875, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37753664

RESUMO

The authors used a meta-analysis to evaluate the risks of gastrointestinal adverse events in the cotreatment of malignant tumors with nivolumab and ipilimumab. The meta-analysis revealed that the most common gastrointestinal adverse event at all grades was diarrhea, followed by nausea, decreased appetite, vomiting, constipation, colitis and abdominal pain. The most common severe gastrointestinal adverse events were colitis and diarrhea. Different administration schemes differ in the risk of such events, and thus these events may be minimized by modulating the administration scheme of the cotreatment.


Assuntos
Colite , Neoplasias , Humanos , Nivolumabe/efeitos adversos , Ipilimumab/efeitos adversos , Neoplasias/tratamento farmacológico , Diarreia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Colite/induzido quimicamente , Colite/tratamento farmacológico
8.
Acta Med Indones ; 55(1): 83-86, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36999261

RESUMO

Leiomyosarcoma commonly occurs in the abdomen, retroperitoneum, large blood vessels, and uterus[1]. Cardiac leiomyosarcoma is a rare and highly aggressive sarcoma. We reported a case of a 63-year-old male with pulmonary artery leiomyosarcoma. Transthoracic echocardiography showed a large 4.4×2.3 cm hypoechoic mass in the right ventricular outflow tract and pulmonary artery. Computed tomography pulmonary angiography showed a filling defect in a similar location. The initial impression was PE, but a tumor was not ruled out. An emergency surgery was performed due to progressively worse chest distress and dyspnea. A yellow mass that had adhered to the ventricular septum and pulmonary artery wall was detected to be compressing the pulmonary valve. Immunohistochemistry confirmed tumor cells positive staining for Desmin and smooth muscle actin and negative staining for S-100, CD34, myogenin, or myoglobin, and KI67(+)80%, indicating leiomyosarcoma. Pulmonary leiomyosarcoma showed a side-inserted heart chamber filling defect in CTA and should be excised when the patient suddenly deteriorated.


Assuntos
Leiomiossarcoma , Neoplasias Pulmonares , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Leiomiossarcoma/diagnóstico por imagem , Leiomiossarcoma/cirurgia , Artéria Pulmonar/patologia , Pulmão , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Imuno-Histoquímica
9.
Eur J Nucl Med Mol Imaging ; 49(4): 1211-1222, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34651221

RESUMO

PURPOSE: The aim of this study was to explore the association of cardiac fibroblast activation with clinical parameters and cardiovascular magnetic resonance (CMR) imaging parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Thirteen CTEPH patients were prospectively enrolled. All of the patients underwent cardiac 68Gallium-labelled fibroblast activation protein inhibitor (68 Ga-FAPI-04)-positron emission tomography/computed tomography (PET/CT), right heart catheterisation, and echocardiography, and 11 of them additionally underwent CMR. Thirteen control subjects were selected to establish the normal range of cardiac 68 Ga-FAPI-04 uptake. Cardiac 68 Ga-FAPI-04 uptake higher than that in the blood pool was defined as abnormal. The global and segmental maximum standardised uptake values (SUVmax) of the right ventricle (RV) were measured and further expressed as target-to-background ratio (TBRRV) with left ventricular lateral wall activity as background. Late gadolinium enhancement (LGE) was visually evaluated, and native-T1 times, enhanced-T1 times, and extracellular volume (ECV) were quantitatively measured. RESULTS: Ten CTEPH patients (77%) had abnormal 68 Ga-FAPI-04 uptake in RV, mainly located in the free wall, which was significantly higher than that in controls (TBRRV: 2.4 ± 0.9 vs 1.0 ± 0.1, P < 0.001). The TBRRV correlated positively with the thickness of RV wall (r = 0.815, P = 0.001) and inversely with RV fraction area change (RVFAC) (r = - 0.804, P = 0.001) and tricuspid annular plane systolic excursion (TAPSE) (r = - 0.678, P = 0.011). No correlation was found between 68 Ga-FAPI-04 activity and CMR imaging parameters. CONCLUSION: Fibroblast activation in CTEPH, measured by 68 Ga-FAPI-04 imaging, is mainly localised in the RV free wall. Enhanced fibroblast activation reflects the thickening of the RV wall and decreased RV contractile function.


Assuntos
Hipertensão Pulmonar , Disfunção Ventricular Direita , Meios de Contraste , Fibroblastos , Gadolínio , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
10.
J Thromb Thrombolysis ; 51(3): 703-710, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32894400

RESUMO

A definitive diagnosis of heparin-induced thrombocytopenia (HIT) is difficult to make, especially in patients undergoing cardiac surgery. In this retrospective cohort study, we assessed the platelet count trends and the response to fondaparinux in a population of patients of suspected HIT after pulmonary endarterectomy (PEA). Patients enrolled in this study were over the age of 18 years, and survived longer than 7 days after PEA between January 1, 2011 and December 31, 2015. HIT likelihood was assessed by the 4 T's score and interpreted by our institutional algorithm. 54 patients were operated, and 49 patients met the inclusion criteria. Six patients met the criteria for suspected HIT and were treated with fondaparinux until the platelet recovered. No significant difference was observed of clinical characteristics between intermediate to high HIT likelihood patients (HIT SUSPECTED) and low HIT likelihood patients (NO HIT SUSPECTED). HIT SUSPECTED patients reached platelet count lowest later (about 5.5 days after PEA), while NO HIT SUSPECTED patients is about 4.0 days after PEA. Percentage of platelet counts decrease (> 50%) was larger than NO HIT SUSPECTED patients (< 50%). There was no difference in mortality or residual pulmonary hypertension between HIT SUSPECTED and NO HIT SUSPECTED patients. Two HIT SUSPECTED patients who used heparin after PEA died, the other four survived by replacing heparin or low molecular weight heparin with fondaparinux. Suspected HIT patients should be surveilled carefully. Platelet counts trends may have some hints in the prevention of HIT. Fondaparinux may be effective for patients with suspected HIT.


Assuntos
Endarterectomia/efeitos adversos , Fondaparinux/administração & dosagem , Heparina/efeitos adversos , Hipertensão Pulmonar , Contagem de Plaquetas , Complicações Pós-Operatórias , Trombocitopenia , Adulto , China/epidemiologia , Estudos de Coortes , Endarterectomia/métodos , Inibidores do Fator Xa/administração & dosagem , Feminino , Heparina/administração & dosagem , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/prevenção & controle , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas/métodos , Contagem de Plaquetas/estatística & dados numéricos , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Embolia Pulmonar/complicações , Embolia Pulmonar/mortalidade , Embolia Pulmonar/cirurgia , Risco Ajustado/métodos , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Trombocitopenia/epidemiologia
11.
Mol Med ; 26(1): 39, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375633

RESUMO

BACKGROUND: Ovarian cancer is the most lethal gynecologic cancer. Chemoresistance, especially platinum-resistance, is closely related to metastasis of ovarian cancer, however, the molecular basis by which links chemoresistance and metastasis remains vague. Disordered arachidonic acid (AA) metabolism has been shown to play an important role in the advanced ovarian cancer. This study aimed to explore the underlying mechanism involving eicosanoid metabolism that controlling chemoresistance and metastasis of ovarian cancer. METHODS: Cisplatin (DDP)-resistant SKOV3 (SKOV3-R) cells were constantly induced. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was performed to determine the AA metabolism in SKOV3 and SKOV3-R cells. Half maximal inhibitory concentration (IC50) and percentage of cell viability were tested using cell counting kit 8 (CCK-8). Realtime quantitative PCR (qPCR) and immunohistochemistry (IHC) were used to evaluate indicated genes and proteins respectively. Bioinformatic analysis and chromatin immunoprecipitation (ChIP) were performed to predict and identify the co-transcription factor of interest genes. Tumor growth and metastasis in the liver were assessed with nude mice by subcutaneously injection of SKOV3-R cells. RESULTS: SKOV3-R cells expressed higher multidrug resistance-associated proteins (MRPs) MRP1 and MRP4. They showed enhanced metastatic ability and produced increased AA-derived eicosanoids. Mechanistically, MRPs, epithelial mesenchymal transition (EMT) markers Snail and Slug, as well as key enzymes involved in AA-metabolism including 12-lipoxygenase (12LOX) were transcribed by the mutual transcription factor SP1 which was consistently upregulated in SKOV3-R cells. Inhibition of SP1 or 12LOX sensitized SKOV3-R cells to DDP and impaired metastasis in vitro and in vivo. CONCLUSION: Our results reveal that SP1-12LOX axis signaling plays a key role in DDP-resistance and metastasis, which provide a new therapeutic target for ovarian cancer.


Assuntos
Araquidonato 12-Lipoxigenase/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Ovarianas/metabolismo , Transdução de Sinais , Fator de Transcrição Sp1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Imuno-Histoquímica , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Modelos Biológicos , Metástase Neoplásica , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia
12.
Psychol Health Med ; 25(1): 78-90, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31132885

RESUMO

Extensive evidence has been obtained that supports an association between an attentional bias (AB) toward negative stimuli and vulnerability to mental and behavioral problems; however, diabetes self-management (DSM) behavior in type 2 diabetic patients has not specifically been assessed. The current study investigated whether type 2 diabetic Chinese patients who had different levels of self-management behaviors showed different patterns of AB toward either positive or negative stimuli. A sample of 195 patients completed questionnaires measuring DSM and a modified dot-probe task measuring AB. Patients with low levels of DSM had an avoidance bias for positive stimuli, the regression showed that negative orienting index significantly predicted lower DSM; patients with medium levels of DSM had difficulty in disengaging attention from negative stimuli, the regression showed that negative disengaging index significantly predicted lower DSM; while patients with high levels of DSM had an avoidance bias for negative stimuli and difficulty in disengaging from positive stimuli. An implication of this finding is that the understanding of information processing bias affects DSM and therefore suggests a novel target for prevention and treatment interventions.


Assuntos
Viés de Atenção/fisiologia , Diabetes Mellitus Tipo 2/psicologia , Diabetes Mellitus Tipo 2/terapia , Emoções/fisiologia , Autogestão , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Eur J Nucl Med Mol Imaging ; 46(10): 1989, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31250084

RESUMO

Figure c of the original version of this article was not converted properly. Correct figure is presented here. The original article has been corrected.

14.
Psychol Health Med ; 23(9): 1125-1136, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29763571

RESUMO

Extensive evidence has been obtained that supports an association between an attentional bias (AB) toward negative stimuli and vulnerability to stress-related psychopathology, little is known regarding the characteristics of individual AB in different posttraumatic growth (PTG) levels. The current study used a modified dot-probe task to investigate if individual differences in AB towards either positive or negative emotional stimuli, are related to self-reported PTG. A sample of 202 patients completed the experiment. Patients with low levels of PTG did not exhibit AB toward negative or positive stimuli, patients with medium levels of PTG had difficulty disengaging attention from negative stimuli, patients with high levels of PTG had difficulty disengaging attention from positive stimuli. And the AB towards positive stimuli was only predictive for PTG. An implication of this finding is that there are different characteristics of implicit cognitive processing in patients with different levels of PTG, suggesting the necessity of psychological intervention on the accidentally injured patients.


Assuntos
Viés de Atenção , Emoções , Crescimento Psicológico Pós-Traumático , Ferimentos e Lesões/psicologia , Acidentes , Acidentes de Trabalho/psicologia , Acidentes de Trânsito/estatística & dados numéricos , Adolescente , Adulto , Idoso , Atenção , China , Cognição , Feminino , Humanos , Individualidade , Masculino , Processos Mentais , Pessoa de Meia-Idade , Autorrelato , Adulto Jovem
15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 35(6): 904-907, 2018 Dec 10.
Artigo em Zh | MEDLINE | ID: mdl-30512176

RESUMO

Cardiac valves are highly organized yet delicate structures that ensure unidirectional blood flow through the cardiac chambers and large vessels. Disturbed development of cardiac valves can lead to aberrant heart formation and function which account for approximately one third of congenital heart diseases. The formation of cardiac valves is a dynamic process accomplished by a series of complex events including lineage determination and cell proliferation, differentiation and migration. This paper reviews current knowledge about the role of Tbx20 gene in the development of cardiac valves, which include functional diversities of Tbx20 at various stages of cardiac valve development, its interaction with other signaling pathways, and genetic network involved in endocardial development.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Valvas Cardíacas/embriologia , Proteínas com Domínio T/genética , Diferenciação Celular , Proliferação de Células , Humanos
18.
J Nerv Ment Dis ; 205(5): 380-389, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27875386

RESUMO

The literature on posttraumatic growth (PTG) is burgeoning, with the inconsistencies in the literature of the relationship between PTG and posttraumatic stress disorder (PTSD) symptoms becoming a focal point of attention. Thus, this meta-analysis aims to explore the relationship between PTG and PTSD symptoms through the Pearson correlation coefficient. A systematic search of the literature from January 1996 to November 2015 was completed. We retrieved reports on 63 studies that involved 26,951 patients. The weighted correlation coefficient revealed an effect size of 0.22 with a 95% confidence interval of 0.18 to 0.25. Meta-analysis provides evidence that PTG may be positively correlated with PTSD symptoms and that this correlation may be modified by age, trauma type, and time since trauma. Accordingly, people with high levels of PTG should not be ignored, but rather, they should continue to receive help to alleviate their PTSD symptoms.


Assuntos
Adaptação Psicológica/fisiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Humanos , Estatística como Assunto
20.
CNS Neurosci Ther ; 30(2): e14632, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38366763

RESUMO

BACKGROUND: Olfactory dysfunction is known to be an early manifestation of Alzheimer's disease (AD). However, the underlying mechanism, particularly the specific molecular events that occur during the early stages of olfactory disorders, remains unclear. METHODS: In this study, we utilized transcriptomic sequencing, bioinformatics analysis, and biochemical detection to investigate the specific pathological and molecular characteristics of the olfactory bulb (OB) in 4-month-old male triple transgenic 3xTg-AD mice (PS1M146V/APPSwe/TauP301L). RESULTS: Initially, during the early stages of olfactory impairment, no significant learning and memory deficits were observed. Correspondingly, we observed significant accumulation of amyloid-beta (Aß) and Tau pathology specifically in the OB, but not in the hippocampus. In addition, significant axonal morphological defects were detected in the olfactory bulb, cortex, and hippocampal brain regions of 3xTg-AD mice. Transcriptomic analysis revealed a significant increase in the expression of neuroinflammation-related genes, accompanied by a significant decrease in neuronal activity-related genes in the OB. Moreover, immunofluorescence and immunoblotting demonstrated an activation of glial cell biomarkers Iba1 and GFAP, along with a reduction in the expression levels of neuronal activity-related molecules Nr4a2 and FosB, as well as olfaction-related marker OMP. CONCLUSION: In sum, the early accumulation of Aß and Tau pathology induces neuroinflammation, which subsequently leads to a decrease in neuronal activity within the OB, causing axonal transport deficits that contribute to olfactory disorders. Nr4a2 and FosB appear to be promising targets for intervention aimed at improving early olfactory impairment in AD.


Assuntos
Doença de Alzheimer , Transtornos do Olfato , Camundongos , Animais , Masculino , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Olfato , Doenças Neuroinflamatórias , Peptídeos beta-Amiloides/metabolismo , Camundongos Transgênicos , Transtornos do Olfato/genética , Modelos Animais de Doenças , Proteínas tau/genética , Proteínas tau/metabolismo
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