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1.
Ann Transplant ; 29: e943610, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39285624

RESUMEN

BACKGROUND This study aimed to evaluate the effectiveness of implementing evidence-based preoperative nursing interventions in reducing postoperative infections and intensive care unit (ICU) length of stay among liver transplant recipients. MATERIAL AND METHODS A controlled study was conducted, comparing postoperative outcomes between an intervention group receiving standardized, evidence-based preoperative care and a control group receiving routine preoperative care. Patients undergoing elective liver transplantation from September 2020 to March 2021 were included and assigned to either the intervention or control group. The intervention group received preoperative interventions based on best available evidence, while the control group received standard preoperative care. The primary outcomes measured were postoperative infection rates and length of ICU stay. RESULTS In the control group the overall Intensive Care Unit (ICU) length of stay was 3 days and the infection rate was 33.30%, while in the intervention group it was 3 days and 13.80% (P<0.05). There was no significant difference in the length of ICU stay between the control and the intervention groups (P>0.05). There was a significant improvement in the awareness, acceptance, and compliance of doctors and nurses. CONCLUSIONS Using the best evidence-based intervention for preoperative nursing of liver transplantation patients can standardize preoperative nursing behavior. Although we did not find significant differences in outcomes before and after the intervention, it is necessary to prevent postoperative infection and improve nursing compliance.


Asunto(s)
Tiempo de Internación , Trasplante de Hígado , Complicaciones Posoperatorias , Cuidados Preoperatorios , Humanos , Trasplante de Hígado/efectos adversos , Femenino , Masculino , Cuidados Preoperatorios/métodos , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Adulto , Práctica Clínica Basada en la Evidencia , Unidades de Cuidados Intensivos
2.
J Multidiscip Healthc ; 17: 4373-4382, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39262823

RESUMEN

Purpose: To investigate and analyse the status quo of the self-management of patients living with HIV/AIDS (PLWHA) and its influencing factors and to provide the basis for formulating intervention strategies. Methods: In this cross-sectional study, 300 PLWHA who visited the Infection Center of Beijing Youan Hospital, Capital Medical University between September 2021 and December 2021 were enrolled using the convenience sampling method. Demographic characteristics and disease-related data were collected for each participant. The HIV/AIDS Self-Management Scale was used to evaluate the self-management ability of PLWHA. Results: A total of 251 male and 49 female PLWHA were included in this study, with an average age of 39.08 ± 12.09 years and an average disease duration of 9.61 ± 37.04 months. Univariate analysis showed that the PLWHA's place of residence, educational level, physical condition, family relations, duration of HIV disease, receipt or not of antiviral therapy and knowledge of disease had an influence on the scores of the HIV Self-Management Scale (all p < 0.05). The results of the self-management scores indicated that the total score for self-management was 41.5 ± 6.4 points, with a scoring rate of 69.6%, which was at a medium level. Long-term self-management had the highest scoring rate (12.2 ± 2.5 points), followed by daily health management (22.3 ± 4.3 points), and social support for self-management had the lowest scoring (5.1 ± 0.9 points). Multivariable analysis showed that the self-management ability of PLWHA was related to educational level, duration of disease and family relations (R2 = 0.67, F = 121.7, p < 0.05). Conclusion: The self-management level of patients with AIDS, especially the social support of daily health management and self-management, needs to be further improved. Educational level, duration of disease and family relations are important factors influencing the self-management of PLWHA.

3.
Huan Jing Ke Xue ; 45(8): 4432-4439, 2024 Aug 08.
Artículo en Chino | MEDLINE | ID: mdl-39168663

RESUMEN

Satellite-based formaldehyde(HCHO)columns and tropospheric nitrogen dioxide columns were observed using the Ozone Monitoring Instrument(OMI),and groundbased observations of ozone(O3)for May-August from 2013 to 2022 were connected to calculate the threshold values of the HCHO to NO2 ratio(FNR)in Shanxi Province. Then,the spatiotemporal distributions and variations in summertime ozone photochemical production regimes were analyzed. The results showed that:① The volatile organic compound(VOC) -sensitive regime area(FNR < 2.3)was obviously reduced,while the VOCs-NOx transitional regime(FNR between 2.3-4.1)area increased in the early years and then decreased, and NO x -sensitive regime area expanded significantly in summer from 2013 to 2022 over Shanxi Province. ② The increased summertime FNR during 2013 to 2019 was associated with the co-effect of increased HCHO columns and decreased tropospheric NO2 columns. The Shanxi Province was generally under an NOx regime since 2016,which reflected the remarkable effect of NO x emission reductions;however,there was a shift from a VOC-sensitive regime to a VOCs-NOx transitional regime,in which O3 pollution aggravation was widespread under the background of decreased NOx emissions. The decrease in O3 concentration during 2020 to 2022 followed the synergistical declines in HCHO columns and tropospheric NO2 columns. ③ The O3 weekend effects were reversed in Linfen and Yuncheng but were persistent in the other nine cities. Satellite-based weekend HCHO and NO2 levels were higher than those on weekdays in some cities of Shanxi Province,indicating that the O3 weekend effect was not only dependent on the changes of precursors emissions but was also closely related to O3 photochemical production sensitivity. The results indicated the necessity of simultaneous controls in NOx emissions and VOCs emissions for ozone abatement plans over Shanxi Province. In addition,Taiyuan,Yangquan,Yuncheng,and Jincheng should continue to promote reduction in NOx emissions.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38959195

RESUMEN

Background: Posterior fossa craniotomy is commonly performed for various pathologies. However, intra-cranial infection following craniotomy causes morbidity. Pseudomeningocele is one of the main complications following posterior fossa operation. This study aimed to test the hypothesis that the risk of intra-cranial infection is increased in patients who undergo posterior fossa craniotomy with pseudomeningocele compared with those without pseudomeningocele. Methods: We retrospectively analyzed the data of patients undergoing posterior fossa craniotomy for the management of neurological pathologies at our institute from 2011 to 2020. A total of 308 craniotomies were included, and the primary outcome of interest was the occurrence of intra-cranial infection. Standard statistical methods were used to explore associations between several parameters, including pseudomeningocele, intra-cranial infection, and wound leak. Results: Of the 308 craniotomies, 41 (13.3%) developed intra-cranial infection and 59 (19.2%) involved pseudomeningocele. Of cases involving pseudomeningocele, 27 (45.8%) developed an intra-cranial infection compared with only 14 of 249 without pseudomeningocele (5.6%; p < 0.001). In the multi-variable analysis, pseudomeningocele was associated with intra-cranial infection (odds ratio [OR] 8.56; 95% confidence interval [CI] 3.145-23.299; p < 0.001) and wound leak (OR 91.339; 95% CI 10.437-799.364; p < 0.001). Conclusion: The findings indicate that patients undergoing posterior fossa craniotomy are at a greater risk of intra-cranial infection if there is pseudomeningocele after the operation.

5.
Chem Biodivers ; 21(7): e202400635, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38687253

RESUMEN

The phytochemical investigation of the fruits of Cornus officinalis yielded a new phenolic acid derivative, neophenolic acid A (1), and a novel flavonoid glycoside, (2R)-naringenin-7-O-ß-(6''-galloyl-glucopyranoside) (2 a), along with six known flavonoid glycosides (2 b-7). Their structures were determined by 1D, 2D NMR and HRESIMS data. The absolute configuration of 1 was established by ECD analysis. Compounds 1- 7 were evaluated for their neuroprotective activities against corticosterone (CORT)-induced injury in PC-12 cells. Compounds 1, 2 a, 2 b, 5, and 6 exhibited neuroprotective activities against CORT-induced neurotoxicity in PC-12 cells. The underlying mechanism study suggested that compounds 1, 2 a, 2 b, 5, and 6 were able to attenuate CORT-induced apoptosis and damage, increase the levels of MMP and decrease Ca2+ inward flow in PC-12 cells.


Asunto(s)
Apoptosis , Cornus , Frutas , Fármacos Neuroprotectores , Cornus/química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Animales , Frutas/química , Ratas , Células PC12 , Apoptosis/efectos de los fármacos , Corticosterona/farmacología , Supervivencia Celular/efectos de los fármacos , Estructura Molecular , Flavonoides/farmacología , Flavonoides/aislamiento & purificación , Flavonoides/química , Relación Estructura-Actividad , Calcio/metabolismo
6.
J Multidiscip Healthc ; 17: 1541-1548, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38623394

RESUMEN

Objective: This study explores the correlation between coping style, quality of life, and illness uncertainty in the family caregivers of patients with liver cancer. Methods: Employing convenience sampling, 210 family caregivers of patients with liver cancer who met the admission criteria were selected from a grade A infectious disease hospital in Beijing between January and December 2022. A cross-sectional survey was conducted using the Simplified Coping Style Questionnaire, Caregiver Quality of Life, and the Mishel Uncertainty in Illness Scale for Family Members. This study analysed the correlations between coping styles, quality of life, and illness uncertainty in these caregivers. Results: The study found that family caregivers of patients with liver cancer had average scores for illness uncertainty (83.44 ± 11.86), coping style (33.19 ± 9.79; both positive [23.02 ± 6.81] and negative [10.17 ± 5.05]), and quality of life (169.53 ± 32.46). A negative association was observed between illness uncertainty in these caregivers and positive coping style (r = -0.207, p = 0.003), physical status (r = -0.182, p = 0.008), psychological status (r = -0.200, p = 0.004), and social adaptation (r = -0.229, p = 0.001). Conclusion: The study concludes that illness uncertainty in family caregivers of patients with liver cancer is at a moderate level. Furthermore, there is a notable correlation between illness uncertainty, coping style, and quality of life in these caregivers.

8.
J Asian Nat Prod Res ; 25(10): 976-982, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36946084

RESUMEN

Two previously undescribed flavonoid thioglucosides lepidiumflavonosides A and B (1-2) and two known megastigmane compounds (7E,9S)-9-hydroxy-5,7-megastigmadien-4-one 9-O-ß-D-glucopyranoside (3) and (9S)-4-oxo-ß-inol ß-D-glucopyranoside (4) were isolated from the water extract of the seeds of Lepidium apetalum Willd. The structural elucidation of isolated compounds was unambiguously determined based on extensive 1D and 2D NMR spectroscopic analyses. All compounds were evaluated for their estrogen-like effects on MCF-7 cells in vitro. The results showed that compounds 1-4 significantly promoted the proliferation of MCF-7 cells, and the proliferation was antagonized by the specific ER antagonist ICI182,780, suggesting that compounds 1-4 might have the estrogen-like effect in vitro potentially.


Asunto(s)
Flavonoides , Lepidium , Flavonoides/farmacología , Flavonoides/química , Tioglucósidos/análisis , Lepidium/química , Estrógenos/farmacología , Semillas/química
9.
Bioresour Technol ; 374: 128785, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36822553

RESUMEN

Sewage treatment mediated by microbial organisms is a promising green trend. However, the complex balance between microbiota stability and highly efficient wastewater treatment requires investigation. This study successfully improved the effectiveness of sewage treatment by resetting the microbial community structure in the activated sludge. Truepera, Methylophaga, unclassified_Fodinicurvataceae, and unclassified_Actinomanarales were the dominant genera, while salinity and NH3-N content were identified as the key environmental factors governing the microbial structure. By optimizing the microflora structure driven by environmental factors, the key minor genera were activated and coordinated with the aforementioned genera, thereby promoting wastewater treatment. Finally, the chemical oxygen demand, NH3-N, and total phosphorus removal rates were improved to 86.8 ± 1.9%, 82.4 ± 4.1%, and 94.8 ± 3.8%, respectively. It provides a new insight to improve the wastewater treatment through setting microbiota by environmental factor driven.


Asunto(s)
Microbiota , Purificación del Agua , Aguas del Alcantarillado/química , Aguas Residuales , Eliminación de Residuos Líquidos , Reactores Biológicos , Nitrógeno
10.
Phytochemistry ; 205: 113505, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36347307

RESUMEN

Fifteen previously undescribed minor iridoid glycosides, including four monomers and eleven dimers, were isolated from the fruits of Cornus officinalis Sieb. et Zucc. Their chemical structures were determined on the basis of spectroscopic data and chemical evidence. All of the isolated compounds were evaluated for their effects of the glucose consumption on the insulin resistant HepG2 cells, and four compounds, named cornuofficinalisides F, H, L, and O, increased the glucose consumption significantly at 10 µM, the EC50 values of them were determined to be 0.898, 1.625, 0.923, and 8.589 µM, respectively. Moreover, the four compounds could improve the ability of glucose uptake significantly in insulin resistant HepG2 cells.


Asunto(s)
Cornus , Glicósidos Iridoides/farmacología , Insulina , Glucosa
11.
Int J Neuropsychopharmacol ; 26(2): 137-148, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36573299

RESUMEN

BACKGROUND: Depression is a prevalent and recurrent psychiatric disorder. Aberrant neural structure and activity play fundamental roles in the occurrence of depression. Mitotic arrest deficient protein (MAD2B) is highly expressed in neurons and may be implicated in synaptic plasticity in the central nervous system. However, the effect of MAD2B in depression, as well as the related molecular mechanism, is uncertain. METHODS: Here, we employed mouse models of depression induced by chronic unpredictable stress exposure or corticosterone (CORT) stimulation. Depression-like behaviors in mice were evaluated by sucrose preference, forced swimming, and tail suspension tests. Hippocampal MAD2B overexpression was mediated by adeno-associated virus 8 containing enhanced green fluorescent protein. In vitro primary neuronal cells were obtained from the hippocampus of rat embryos and were treated with CORT, and MAD2B overexpression was performed using lentivirus. MAD2B and glutamate metabotropic receptor 4 (GRM4) levels were evaluated by western blots and quantitative PCR. Primary neuronal miR-29b-3p expression was detected by quantitative PCR. RESULTS: MAD2B expression was reduced in the hippocampus in mice exhibiting depressive-like behaviors. However, hippocampal MAD2B overexpression protected mice from developing either chronic unpredictable stress- or CORT-induced depression-like behaviors, an effect associated with reduced expression of GRM4, a presynaptic receptor involved in depression. Moreover, MAD2B overexpression in primary neuronal cells also decreased GRM4 expression while enhancing the level of miR-29b-3p; this phenomenon was also observed under CORT stimulation. CONCLUSIONS: Our results suggest an important role of neuronal MAD2B in the pathogenesis of depression via the miR-29b-3p/GRM4 signaling pathway. MAD2B could be a potential therapeutic target for depressive disorders.


Asunto(s)
Depresión , MicroARNs , Ratones , Ratas , Animales , Depresión/tratamiento farmacológico , Corticosterona/metabolismo , Hipocampo , Modelos Animales de Enfermedad , MicroARNs/metabolismo , Estrés Psicológico
12.
Huan Jing Ke Xue ; 43(7): 3423-3438, 2022 Jul 08.
Artículo en Chino | MEDLINE | ID: mdl-35791528

RESUMEN

In this study, we analyzed the hourly concentration data of PM10 and PM2.5 in major cities in Jinzhong basin from 2017 to 2019. The main distribution characteristics of aerosols in Jinzhong and Taiyuan were determined, and PM2.5 hourly concentration data and HYSPLIT in Jinzhong basin in winter were discussed. The results showed that the overall level of particulate matter concentration in Taiyuan was higher than that in Jinzhong, and the monthly and seasonal variation characteristics were similar. All showed high concentrations in winter and low concentrations in summer, and the highest concentration value appeared in January. The aerosol pollution caused by the static and stable weather in Jinzhong was more common than that caused by the sand and dust weather in Taiyuan. The distribution of particulate matter showed the characteristics of more intermediate values in Jinzhong and more high and fewer low values in Taiyuan, and winter was the highest incidence season of PM2.5 pollution in Jinzhong basin. PM2.5 transmission passageways in the main cities of Jinzhong basin in winter could be divided into four categories:class 1 was transmitted along the transverse valley of Taihang Mountain, and class 2 was the southeast transmission channel. Class 1 and class 2 were the short-range transmission passageways; air masses carried more moisture, and PM2.5 transmitted along such passageways allowed moisture to be absorbed more easily, increasing levels and aggravating local pollution. Class 3 was the northwest passageway, corresponding to the most serious pollution period of PM2.5 in Jinzhong basin before the arrival of cold air, which also corresponded to the dust transmission passageway. Class 4 was the Fenwei Plain passageway, corresponding to high-concentration PM2.5 pollution. Areas with dense pollution tracks (more than 100 pollution tracks) and areas with slow air flow movement (RTA pollution track end points greater than 50) easily became potential source areas of target cities (PSCF contribution greater than 0.7). The main potential source areas of PM2.5 in winter in Jinzhong (PSCF contributing more than 0.7) were mainly distributed in Linfen, Jincheng, and other places in Shanxi province, as well as in the north of Henan province, the south of Hebei province, and central and south Shaanxi province. The distribution range of main potential source areas of PM2.5 in Taiyuan in winter was wider than that in Jinzhong, including the south of Lvliang, Yangquan, Linfen, and Yuncheng and the south of Jinzhong in Shanxi, as well as most areas in southern Shaanxi, northern Henan province, and southern Hebei province. In addition, the PSCF distribution of high-value centers above 0.9 was wider than that of Jinzhong. When pollution occurs in cities that PSCF contributed more than 0.9, special attention should be paid to the influence of mutual transmission between them and cities in Jinzhong basin. Jinzhong and Taiyuan showed different distribution characteristics corresponding to the surface wind direction when light and higher pollution occur, when the wind direction near the ground in Jinzhong was E, the frequency of light and higher pollution was 8.1%; it was the highest in all wind directions. When the wind direction near the ground in Taiyuan was SSW, the frequency of light to higher polluted weather was the highest in all wind directions (5.1%). In the case of calm wind, the frequency of light to higher pollution in Taiyuan (3.4%) was higher than that in Jinzhong (0.5%).


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Ciudades , Polvo/análisis , Monitoreo del Ambiente/métodos , Material Particulado/análisis , Estaciones del Año
13.
Transl Androl Urol ; 11(12): 1715-1728, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36632166

RESUMEN

Background: Bladder cancer (BC) is the most common malignant tumor of the urinary system. Gemcitabine resistance partly accounts for treatment failure and recurrence in BC. Immunological cell death (ICD) is correlated with chemoresistance. The prognosis of patients with similar tumor stage still varies in response to chemotherapy, recurrence, and disease progression. Therefore, our study aimed to provide a prognostic model based on ICD-related and gemcitabine-resistance genes for BC. Methods: The data of BC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs), and differentially expressed gemcitabine resistance-related genes (DEGRRGs) were identified using the edgeR package. The survival-associated DEGRRGs were identified by univariate Cox analysis. A prognostic model was established by univariate Cox regression analysis and validated by GEO dataset. The outcome of low-risk group and high-risk group was analyzed by the Kaplan-Meier curve. The relationship between risk score and immune cell infiltration was investigated using the TIMER online database. Results: The prognosis of patients in the ICD-high group was significantly better than ICD-low group. A prognostic model containing 5 gemcitabine resistance-related ICD-associated genes, including PTPRR, HOXB3, SIGLEC15, UNC5CL, and CASQ1, was established. In both TCGA prognostic model and GEO validation model, patients in the low-risk group had better outcomes than high-risk group. According to the receiver operating characteristic (ROC) curves, the risk score area under ROC curve (AUC) of the TCGA prognostic model were calculated to be 0.705, while the risk score of the GEO validation model were calculated to be 0.716. Patients in the high-risk group had a significantly higher immune score, stromal score, and infiltration of M0 macrophages, M1 macrophages, M2 macrophages, and activated CD4+ T cells. Patients in the high-risk group had significantly lower infiltration of the regulatory T cells, resting dendritic cell (DCs), and activated DCs. Conclusions: The present study highlighted the functional role of gemcitabine resistance-related ICD-associated genes, constructed a prognostic score for the outcome evaluation and searched for potential targets to overcome gemcitabine chemoresistance in BC.

14.
Front Cell Neurosci ; 15: 722028, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34720877

RESUMEN

Microglia are brain resident macrophages, which actively survey the surrounding microenvironment and promote tissue homeostasis under physiological conditions. During this process, microglia participate in synaptic remodeling, neurogenesis, elimination of unwanted neurons and cellular debris. The complex interplay between microglia and neurons drives the formation of functional neuronal connections and maintains an optimal neural network. However, activation of microglia induced by chronic inflammation increases synaptic phagocytosis and leads to neuronal impairment or death. Microglial dysfunction is implicated in almost all brain diseases and leads to long-lasting functional deficiency, such as hippocampus-related cognitive decline and hypothalamus-associated energy imbalance (i.e., obesity). High-fat diet (HFD) consumption triggers mediobasal hypothalamic microglial activation and inflammation. Moreover, HFD-induced inflammation results in cognitive deficits by triggering hippocampal microglial activation. Here, we have summarized the current knowledge of microglial characteristics and biological functions and also reviewed the molecular mechanism of microglia in shaping neural circuitries mainly related to cognition and energy balance in homeostatic and diet-induced inflammatory conditions.

15.
Front Cell Infect Microbiol ; 11: 696554, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34595127

RESUMEN

The circadian clock regulates numerous key physiological processes and maintains cellular, tissue, and systemic homeostasis. Disruption of circadian clock machinery influences key activities involved in immune response and brain function. Moreover, Immune activation has been closely linked to neurodegeneration. Here, we review the molecular clock machinery and the diurnal variation of immune activity. We summarize the circadian control of immunity in both central and peripheral immune cells, as well as the circadian regulation of brain cells that are implicated in neurodegeneration. We explore the important role of systemic inflammation on neurodegeneration. The circadian clock modulates cellular metabolism, which could be a mechanism underlying circadian control. We also discuss the circadian interventions implicated in inflammation and neurodegeneration. Targeting circadian clocks could be a potential strategy for the prevention and treatment of inflammation and neurodegenerative diseases.


Asunto(s)
Relojes Circadianos , Encéfalo , Ritmo Circadiano , Homeostasis , Humanos , Inflamación
16.
BMC Neurol ; 21(1): 381, 2021 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-34600516

RESUMEN

BACKGROUND: Alzheimer's disease (AD) is a pervasive age-related and highly heritable neurodegenerative disorder but has no effective therapy. The complex cellular microenvironment in the AD brain impedes our understanding of pathogenesis. Thus, a comprehensive investigation of cell type-specific responses in AD is crucial to provide precise molecular and cellular targets for therapeutic development. METHODS: Here, we integrated analyzed 4,441 differentially expressed genes (DEGs) that were identified from 263,370 single-cells in cortex samples by single-nucleus RNA sequencing (snRNA-seq) between 42 AD-pathology subjects and 39 normal controls within 3 studies. DEGs were analyzed in microglia, astrocytes, oligodendrocytes, excitatory neurons, inhibitory neurons, and endothelial cells, respectively. In each cell type, we identified both common DEGs which were observed in all 3 studies, and overlapping DEGs which have been seen in at least 2 studies. Firstly, we showed the common DEGs expression and explained the biological functions by comparing with existing literature or multil-omics signaling pathways knowledgebase. We then determined the significant modules and hub genes, and explored the biological processes using the overlapping DEGs. Finally, we identified the common and distinct dysregulated pathways using overall DEGs and overlapping DEGs in a cell type-specific manner. RESULTS: Up-regulated LINGO1 has been seen in both oligodendrocytes and excitatory neurons across 3 studies. Interestingly, genes enriched in the mitochondrial module were up-regulated across all cell types, which indicates mitochondrial dysfunction in the AD brain. The estrogen signaling pathway seems to be the most common pathway that is disrupted in AD. CONCLUSION: Together, these analyses provide detailed information of cell type-specific and overall transcriptional changes and pathways underlying the human AD-pathology. These findings may provide important insights for drug development to tackle this disease.


Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/genética , Encéfalo , Células Endoteliales , Perfilación de la Expresión Génica , Humanos , Transducción de Señal
17.
Mol Psychiatry ; 26(11): 6336-6349, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34050326

RESUMEN

Microglia play a critical role in maintaining neural function. While microglial activity follows a circadian rhythm, it is not clear how this intrinsic clock relates to their function, especially in stimulated conditions such as in the control of systemic energy homeostasis or memory formation. In this study, we found that microglia-specific knock-down of the core clock gene, Bmal1, resulted in increased microglial phagocytosis in mice subjected to high-fat diet (HFD)-induced metabolic stress and likewise among mice engaged in critical cognitive processes. Enhanced microglial phagocytosis was associated with significant retention of pro-opiomelanocortin (POMC)-immunoreactivity in the mediobasal hypothalamus in mice on a HFD as well as the formation of mature spines in the hippocampus during the learning process. This response ultimately protected mice from HFD-induced obesity and resulted in improved performance on memory tests. We conclude that loss of the rigorous control implemented by the intrinsic clock machinery increases the extent to which microglial phagocytosis can be triggered by neighboring neurons under metabolic stress or during memory formation. Taken together, microglial responses associated with loss of Bmal1 serve to ensure a healthier microenvironment for neighboring neurons in the setting of an adaptive response. Thus, microglial Bmal1 may be an important therapeutic target for metabolic and cognitive disorders with relevance to psychiatric disease.


Asunto(s)
Factores de Transcripción ARNTL , Dieta Alta en Grasa , Memoria , Microglía , Obesidad , Factores de Transcripción ARNTL/genética , Factores de Transcripción ARNTL/metabolismo , Animales , Ritmo Circadiano/fisiología , Dieta Alta en Grasa/efectos adversos , Técnicas de Silenciamiento del Gen , Hipocampo/metabolismo , Hipocampo/fisiología , Aprendizaje/fisiología , Memoria/fisiología , Ratones , Ratones Endogámicos C57BL , Microglía/metabolismo , Obesidad/etiología , Obesidad/genética , Obesidad/metabolismo , Obesidad/prevención & control , Fagocitosis/fisiología , Proopiomelanocortina/metabolismo , Estrés Fisiológico/fisiología
18.
Front Immunol ; 11: 586399, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33363534

RESUMEN

Microglia are brain immune cells responsible for immune surveillance. Microglial activation is, however, closely associated with neuroinflammation, neurodegeneration, and obesity. Therefore, it is critical that microglial immune response appropriately adapts to different stressors. The circadian clock controls the cellular process that involves the regulation of inflammation and energy hemostasis. Here, we observed a significant circadian variation in the expression of markers related to inflammation, nutrient utilization, and antioxidation in microglial cells isolated from mice. Furthermore, we found that the core clock gene-Brain and Muscle Arnt-like 1 (Bmal1) plays a role in regulating microglial immune function in mice and microglial BV-2 cells by using quantitative RT-PCR. Bmal1 deficiency decreased gene expression of pro-inflammatory cytokines, increased gene expression of antioxidative and anti-inflammatory factors in microglia. These changes were also observed in Bmal1 knock-down microglial BV-2 cells under lipopolysaccharide (LPS) and palmitic acid stimulations. Moreover, Bmal1 deficiency affected the expression of metabolic associated genes and metabolic processes, and increased phagocytic capacity in microglia. These findings suggest that Bmal1 is a key regulator in microglial immune response and cellular metabolism.


Asunto(s)
Factores de Transcripción ARNTL/inmunología , Relojes Circadianos/fisiología , Microglía/inmunología , Microglía/metabolismo , Factores de Transcripción ARNTL/deficiencia , Animales , Encéfalo/inmunología , Encéfalo/metabolismo , Inflamación/inmunología , Inflamación/metabolismo , Ratones , Ratones Noqueados
19.
Front Public Health ; 8: 507785, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33344394

RESUMEN

Purpose: The number of families who lost their only child was over one million in 2012 in China, and it is growing rapidly every year. Without their only child, they will inevitably worry about their health and life for their later years. It is important to explore the quality of life and influencing factors of the parents. Methods: The cluster sampling method was adopted to select the participants in Wuhu city, Anhui province, central China. The generalized linear regression models were performed to analyze factors influencing EQ-VAS scores. Results: The parents with different monthly income (P = 0.001) and self-rated health status (P < 0.001) had different EQ-VAS scores. Educational level, self-rated health status, number of chronic diseases, depression and having grandchildren were significantly associated with their EQ-VAS score. Conclusion: The government should encourage public medical institutions to provide convenient health management and medical services to this vulnerable group. Priority treatment should be given to the parents who already have multiple diseases. The parents who were depressed should be given timely intervention. The government should give more financial subsidies to the parents who need to raise their grandchildren.


Asunto(s)
Hijo Único , Calidad de Vida , Niño , China , Estudios Transversales , Humanos , Padres
20.
Front Immunol ; 11: 550145, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33101272

RESUMEN

Microglia are the immune cells of the brain. Hyperactivation of microglia contributes to the pathology of metabolic and neuroinflammatory diseases. Evidence has emerged that links the circadian clock, cellular metabolism, and immune activity in microglia. Rev-erb nuclear receptors are known for their regulatory role in both the molecular clock and cell metabolism, and have recently been found to play an important role in neuroinflammation. The Rev-erbα agonist SR9011 disrupts circadian rhythm by altering intracellular clock machinery. However, the exact role of Rev-erbα in microglial immunometabolism remains to be elucidated. In the current study, we explored whether SR9011 also had such a detrimental impact on microglial immunometabolic functions. Primary microglia were isolated from 1-3 days old Sprague-Dawley rat pups. The expression of clock genes, cytokines and metabolic genes was evaluated using RT-PCR and rhythmic expression was analyzed. Phagocytic activity was determined by the uptake capacity of fluorescent microspheres. Mitochondria function was evaluated by measuring oxygen consumption rate and extracellular acidification rate. We found that key cytokines and metabolic genes are rhythmically expressed in microglia. SR9011 disturbed rhythmic expression of clock genes in microglia. Pro-inflammatory cytokine expression was attenuated by SR9011 during an immune challenge by TNFα, while expression of the anti-inflammatory cytokine Il10 was stimulated. Moreover, SR9011 decreased phagocytic activity, mitochondrial respiration, ATP production, and metabolic gene expression. Our study highlights the link between the intrinsic clock and immunometabolism of microglia. We show that Rev-erbα is implicated in both metabolic homeostasis and the inflammatory responses in microglia, which has important implications for the treatment of metabolic and neuroinflammatory diseases.


Asunto(s)
Metabolismo Energético/efectos de los fármacos , Inmunidad/efectos de los fármacos , Microglía/efectos de los fármacos , Microglía/inmunología , Microglía/metabolismo , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/antagonistas & inhibidores , Pirrolidinas/farmacología , Tiofenos/farmacología , Animales , Proteínas CLOCK/genética , Citocinas/genética , Regulación de la Expresión Génica/efectos de los fármacos , Inmunidad Innata/efectos de los fármacos , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Mitocondrias/metabolismo , Fagocitosis/efectos de los fármacos , Fagocitosis/inmunología , Ratas
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