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1.
Front Public Health ; 10: 825279, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35570958

RESUMO

Medical students' perceptions of the medical school learning environment (MSLE) have an important impact on their professional development, and physical and mental health. Few studies reported potential factors that influenced medical students' perceptions of MSLE. Thus, the main goal of this study was to identify influencing factors for medical students' perception levels of MSLE. The perception levels of MSLE were assessed by the Johns Hopkins Learning Environment Scale. The univariate and multivariate logistic regression analyses were performed to identify significant predictors for the perceptions of MSLE. The nomograms were established to predict medical students' perception levels of MSLE. In the multivariate logistic regression model, gender, university category, grade, mother education level, learning environment of schools, interests in medicine, and Kolb learning experience were significantly associated with medical students' perceptions of MSLE. Correspondently, the nomograms were built based on significant variables identified by the univariate logistic regression analysis. The validation of the nomograms showed that the model had promising predictive accuracy, discrimination, and accordance (area under the curve (AUC) = 0.751). This study identified influencing factors of medical students' perceptions of MSLE. It is essential to implement corresponding interventions to improve medical students' perceptions.

2.
BMC Plant Biol ; 22(1): 250, 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35596150

RESUMO

Hemp (Cannabis sativa L.), an ancient crop, is a significant source of high-quality fiber that primarily caters to the textile industry worldwide. Fiber content is a crucial quantitative trait for evaluating fiber yield in hemp. Understanding the genetic mechanisms involved in hemp breeding is essential for improving yield. In this study, we developed 660 F1 plants from a cross between Jindao-15 (high fiber content fiber-use variety) and Fire No.1 (low fiber content fiber-use variety), and thirty plants each with high and low fiber content were selected from 305 monoecious plants of this population according to 5%-10% of population size for quantitative traits. The DNA from these plants was extracted to establish two bulk DNA pools and then subjected to the restriction digestion by the enzymes RsaI and HaeIII to obtain 314-364 bp digestion fragments and subjected to sequencing using specific length amplified fragment sequencing (SLAF-seq). Finally, we successfully developed 368,404 SLAF tags, which led to the detection of 25,133 high-quality SNPs. Combing with the resequencing results of parents, the SNPs of mixed pools were then subjected to the SNP-Index correlation algorithm, which revealed four candidate regions related to fiber content traits on Chromosome 1, with a length of 8.68 Mb and containing 389 annotated genes. The annotation information and the comparison results identified 15 genes that were highly likely to modulate the fiber content of hemp. Further, qPCR validation identified six genes (LOC115705530, LOC115705875, LOC115704794, LOC115705371, LOC115705688 and LOC115707511) that were highly positively correlated with influencing the hemp fiber content. These genes were involved in the transcription regulation, auxin and water transportion, one carbon and sugar metabolism. And non-synnoumous mutation SNPs which may play vital role in influencing the fiber content were detected in LOC115705875, LOC115704794, LOC115705688 and LOC115707511. Thus, our study highlights the importance of the combined use of SLAF-Seq and Bulked Segregant analysis (BSA) to locate genes related to hemp fiber content rapidly. Hence, our study provides novel mechanistic inputs for the fast identification of genes related to important agronomic traits of hemp and other crops catering to the textile industry.


Assuntos
Cannabis , Locos de Características Quantitativas , Cannabis/genética , Cromossomos de Plantas , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único/genética , Análise de Sequência de DNA
3.
J Clin Epidemiol ; 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35537604

RESUMO

OBJECTIVE: Nutritional screening tools should be sensitive, simple, and easy to use. Differing opinions among clinicians concern the simplicity of the three tools - the Global Leadership Initiative on Malnutrition (GLIM) criteria, Nutritional Risk Screening 2002 (NRS-2002) and Patient Generated Subjective Global Assessment (PG-SGA). For each tool, we estimate prediction of overall survival (OS) in tumor staging, sensitivity, specificity. NRS-2002 is favored by clinicians because it is simple to use. We compare its sensitivity and specificity with GLIM and PG-SGA STUDY DESIGN AND SETTING: This is an analysis of data from 1358 adult colorectal cancer patients recruited in a multicenter from July 2013 to July 2018. RESULTS: In Kaplan-Meier Models, each tool was found to be significantly predictive of overall survival - NRS-2002 (1.28), GLIM (1.49) and PG-SGA (1.42). Use of any tool improved prediction of survival at tumor staging. NRS-2002 has superior specificity (0.90) to diagnose patients without nutritional deficits (GLIM 0.62, PG-SGA 0.82). CONCLUSION: This study provides evidence for the superiority of NRS-2002 accurately identify colorectal cancer patients without nutritional limitations. Compared with the complexity of the other tools, NRS-2002 is simplest to use in routine nutritional screening. in busy clinical practice.

4.
Environ Int ; 165: 107301, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35598418

RESUMO

BACKGROUND: Evidence on the effects of the air pollutants on the hospital admissions, hospital cost and length of stay (LOS) among patients with comorbidities remains limited in China, particularly for patients with cardiovascular diseases and comorbid diabetes mellitus (CVD-DM). METHODS: We collected daily data on CVD-DM patients from 242 hospitals in Beijing between 2014 and 2019. Generalized additive model was employed to quantify the associations between admissions, LOS, and hospital cost for CVD-DM patients and air pollutants. We further evaluated the attributable risk posed by air pollutants to CVD-DM patients, using both Chinese and WHO air quality guidelines as reference. RESULTS: Per 10 ug/m3 increase of particles with an aerodynamic diameter < 2.5 µm (PM2.5), particles with an aerodynamic diameter < 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbonic oxide (CO) and ozone (O3) corresponded to a 0.64% (95% CI: 0.57 to 0.71), 0.52% (95% CI: 0.46 to 0.57), 0.93% (95% CI: 0.67 to 1.20), 0.98% (95% CI: 0.81 to 1.16), 1.66% (95% CI: 1.18 to 2.14) and 0.53% (95% CI: 0.45 to 0.61) increment for CVD-DM patients' admissions. Among the six pollutants, particulate pollutants (PM2.5 and PM10) in most lag days exhibited adverse effects on LOS and hospital cost. For every 10 ug/m3 increase in PM2.5 and PM10, the absolute increase with LOS will increase 62.08 days (95% CI: 28.93 to 95.23) and 51.77 days (95% CI:22.88 to 80.66), respectively. The absolute increase with hospital cost will increase 105.04 Chinese Yuan (CNY) (95% CI: 49.27 to 160.81) and 81.76 CNY (95% CI: 42.01 to 121.51) in PM2.5 and PM10, respectively. Given WHO 2021 air quality guideline as the reference, PM2.5 had the maximum attributable fraction of 3.34% (95% CI: 2.94% to 3.75%), corresponding to an avoidable of 65,845 (95% CI: 57,953 to 73,812) patients with CVD-DM. CONCLUSION: PM2.5 and PM10 are positively associated with hospital admissions, hospital cost and LOS for patients with CVD-DM. Policy changes to reduce air pollutants exposure may reduce CVD-DM admissions and substantial savings in health care spending and LOS.

5.
J Exp Bot ; 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35429161

RESUMO

Flag leaf senescence is an important biological process that drives the remobilization of nutrients to the growing organs of rice. Leaf senescence is controlled by genetic information via gene expression and histone modification, but the precise mechanism is yet unclear. Here, we analyzed genome-wide acetylated lysine residue 9 of histone H3 (H3K9ac) enrichment by chromatin immunoprecipitation-sequencing (ChIP-seq) and examined its association with transcriptomes by RNA-seq during flag leaf aging in rice (Oryza sativa). We found that genome-wide H3K9 acetylation levels increased with age-dependent senescence in rice flag leaf, and there was a positive correlation between the density and breadth of H3K9ac with gene expression and transcript elongation. A set of 1,249 up-regulated, differentially expressed genes (DEGs) and 996 down-regulated DEGs showing a strong relationship between temporal changes in gene expression and gain/loss of H3K9ac was observed during rice flag leaf aging. We produced a landscape of H3K9 acetylation- modified gene expression targets that includes known senescence-associated genes, metabolism-related genes, as well as miRNA biosynthesis- related genes. Our findings reveal a complex regulatory network of metabolism- and senescence-related pathways mediated by H3K9ac and elucidate patterns of H3K9ac-mediated regulation of gene expression during flag leaf aging in rice.

6.
Hematol Oncol ; 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35416325

RESUMO

Sustained expression of B-cell receptor (BCR) critically contributes to the development of diffuse large B-cell lymphoma (DLBCL). However, little is known on the mechanism regulating BCR expression. In the present study, we explored the biological significance of functional intergenic repeating RNA element (FIRRE) in DLBCL and its regulation on BCR. Functional impacts of FIRRE on cell viability, transformation, and apoptosis were examined by MTT, colony formation, and flow cytometry, respectively. The interaction between FIRRE and polypyrimidine tract binding protein 1 (PTBP1) was identified by RNA pull-down and verified using RNA immunoprecipitation (RIP) assays. The effects of FIRRE and PTBP1 on Smurf2 mRNA were examined by RIP, RNA pull-down, and mRNA stability assays. Smurf2-mediated BCR ubiquitination was investigated using co-immunoprecipitation, ubiquitination, and protein stability assays. In vivo, xenograft models were used to assess the impacts of targeting FIRRE on DLBCL growth. FIRRE was specifically up-regulated in and essentially maintained multiple malignant behaviors of BCR-dependent DLBCL cells. Through the interaction with PTBP1, FIRRE promoted the mRNA decay of Smurf2, a ubiquitin ligase for the degradation BCR protein. Targeting FIRRE was sufficient to regulat Smurf2 and BCR expressions and inhibit DLBCL malignancy both in vivo and in vitro. FIRRE-PTBP1 interaction, by simulating Smurf2 mRNA decay and stabilizing BCR, promotes the development of DLBCL. Consequently, targeting this signaling mechanism may provide therapeutic benefits for DLBCL.

7.
J Sci Food Agric ; 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35398898

RESUMO

BACKGROUND: In this study the potential of liposomes as a vitamin E (VE) and ß-carotene (ßC) delivery system was examined. The co-encapsulated liposomes of ßC and VE (L-VE-ßC) were prepared and characterized. Their antioxidant properties were evaluated by free radical scavenging activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), hydroxyl radical and lipid peroxidation assay. The in vitro sustained release behaviour was then investigated and discussed. RESULTS: VE and ßC were co-encapsulated in liposomes with high encapsulation efficiency, up to 92.49% and 86.16% for ßC and VE, respectively. The antioxidant activities of L-VE-ßC samples were significantly higher than that of single loaded liposome. Among different ratios of VE/ßC, L-VE-ßC at 5:3 exhibited the highest radical scavenging rates, with 66.80%, 56.58% and 34.39% for DPPH, ABTS and OH radical, respectively. L-VE-ßC samples also had a good ability to inhibit lipid peroxidation, especially the sample with ratios of VE/ßC at 5:3 and 3:1. In simulated gastrointestinal release, L-VE-ßC exhibited an excellent sustained release behaviour in SGF with the accumulated rate at about 20%, while the release rate in SIF increased to over 80%, where they should be absorbed. The release kinetics analysis indicated that ßC was released in the Higuchi model in stomach, and the Korsmeyr-Peppas model in intestine. CONCLUSION: Compared to single loaded liposomes, the combined-loaded liposomes exhibited higher antioxidant activity and bioavailability, suggesting the potential applications in functional foods. © 2022 Society of Chemical Industry.

8.
Waste Manag ; 144: 221-232, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35397419

RESUMO

Due to rapid economic development and urbanisation, emerging megacities with dense populations have witnessed a significant increase in waste generation. Megacities face challenges in developing sustainable waste management systems. Considerable heterogeneity exists across megacities in management strategies. The two selected emerging megacities, Singapore (a city-state) and Shanghai, have similar developmental characteristics, but their waste management modes differ strikingly. This study assessed the two modes in terms of management strategies, environmental effects, economic costs, and social outcomes. Environmental footprint analysis and cost quantification were employed for the assessment based on public data. The research results would permit a deeper understanding of the long-term sustainability of each mode while considering the feasibility of implementation across different contexts. It was found that the waste management system in Singapore had a relatively lower environmental impact than Shanghai before Shanghai's new waste segregation and recycling policy in 2019. However, when the effect of fossil fuel substitution is taken into account, the environmental burden in Shanghai can be lowered more substantially than the one in Singapore. Although Shanghai had more economic burden for the waste segregation at source, it tended to implement the circular economy principles (e.g., reduce, reuse, and recycling) better and improve its sense of community significantly. Based on the practical experiences from the two representative megacities, suggestions for better waste management practices were provided for Singapore, Shanghai, and other emerging megacities with similar circumstances. In addition, challenges and opportunities related to household waste segregation and recycling were identified to guide future practices in emerging megacities.


Assuntos
Eliminação de Resíduos , Gerenciamento de Resíduos , China , Cidades , Reciclagem , Singapura , Resíduos Sólidos/análise
9.
Environ Sci Technol ; 56(7): 4187-4198, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35289167

RESUMO

Biochar application is a promising strategy for the remediation of contaminated soil, while ensuring sustainable waste management. Biochar remediation of heavy metal (HM)-contaminated soil primarily depends on the properties of the soil, biochar, and HM. The optimum conditions for HM immobilization in biochar-amended soils are site-specific and vary among studies. Therefore, a generalized approach to predict HM immobilization efficiency in biochar-amended soils is required. This study employs machine learning (ML) approaches to predict the HM immobilization efficiency of biochar in biochar-amended soils. The nitrogen content in the biochar (0.3-25.9%) and biochar application rate (0.5-10%) were the two most significant features affecting HM immobilization. Causal analysis showed that the empirical categories for HM immobilization efficiency, in the order of importance, were biochar properties > experimental conditions > soil properties > HM properties. Therefore, this study presents new insights into the effects of biochar properties and soil properties on HM immobilization. This approach can help determine the optimum conditions for enhanced HM immobilization in biochar-amended soils.


Assuntos
Recuperação e Remediação Ambiental , Metais Pesados , Poluentes do Solo , Carvão Vegetal , Aprendizado de Máquina , Solo , Poluentes do Solo/análise
10.
J Healthc Eng ; 2022: 7727953, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35310197

RESUMO

Objective: To explore the effect of integrated nursing care based on the medical alliance model on prevention and treatment of complications and self-efficacy in patients with coronary heart disease (CHD) after PCI. Methods: The data of CHD patients treated in our hospital from January 2019 to January 2021 were analyzed in this retrospective study. One hundred and twenty patients were selected as the research subjects according to the inclusion and exclusion criteria and equally split into the observation group and reference group according to the order of admission. Both groups received routine nursing care, while the observation group was additionally given integrated nursing care based on the medical alliance model to compare the self-efficacy scores, scores of self-management abilities, and incidence of postoperative complications between the two groups before and after nursing. Both groups were nursed for 6 months. Results: Compared with the reference group, the observation group after nursing achieved a notably higher GSES score (26.10 ± 1.30 vs 22.18 ± 1.30, t = 16.516, P < 0.001), higher scores of self-management ability (P < 0.001) , and a lower incidence of postoperative complications (P < 0.05). Conclusion: Integrated nursing care based on the medical alliance model can improve the self-efficacy of CHD patients undergoing PCI, enhance their self-management ability, and reduce the incidence of postoperative complications, which is conducive to improving the prognosis of patients.


Assuntos
Doença das Coronárias , Intervenção Coronária Percutânea , Doença das Coronárias/cirurgia , Humanos , Complicações Pós-Operatórias , Qualidade de Vida , Estudos Retrospectivos , Autoeficácia
11.
Int J Pharm ; 619: 121688, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35314278

RESUMO

Pharmacokinetic limitations associated with oral ivermectin may limit its success as a potential COVID-19 treatment based on in vitro experiments which demonstrate antiviral efficacy against SARS-CoV-2 at high concentrations. Targeted delivery to the lungs is a practical way to overcome these limitations and ensure the presence of a therapeutic concentration of the drug in a clinically critical site of viral pathology. In this study, the pharmacokinetics (PK) and safety of inhaled dry powders of ivermectin with lactose were investigated in healthy mice. Female BALB/c mice received ivermectin formulation by intratracheal administration at high (3.15 mg/kg) or low doses (2.04 mg/kg). Plasma, bronchoalveolar lavage fluid (BALF), lung, kidney, liver, and spleen were collected at predetermined time points up to 48 h and analyzed for PK. Histological evaluation of lungs was used to examine the safety of the formulation. Inhalation delivery of ivermectin formulation showed improved pharmacokinetic performance as it avoided protein binding encountered in systemic delivery and maintained a high exposure above the in vitro antiviral concentration in the respiratory tract for at least 24 h. The local toxicity was mild with less than 20% of the lung showing histological damage at 24 h, which resolved to 10% by 48 h.


Assuntos
COVID-19 , Administração por Inalação , Animais , Antivirais , COVID-19/tratamento farmacológico , Inaladores de Pó Seco , Feminino , Humanos , Ivermectina , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Pós/metabolismo , SARS-CoV-2
12.
Contrast Media Mol Imaging ; 2022: 3318223, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35350701

RESUMO

This study focused on the application value of the newly prepared 129Xe nanoprobe-based functional magnetic resonance imaging (fMRI) in exploring the mechanism of the acupuncture treatment for intractable facial paralysis, expected to provide a theoretical reference for the mechanism of acupuncture for the treatment of facial paralysis. In this study, 30 patients with intractable peripheral facial paralysis (experimental group) and 30 healthy volunteers (control group) were selected. All patients were scanned by the newly prepared 129Xe nanoprobe-based fMRI technology, and then brain functional status data and rating data were collected. fMRI scanning results showed that multiple brain regions were activated in the experimental group before treatment, among which the central posterior brain, insula, and thalamus were positively activated, while the precuneus, superior frontal gyrus, and other parts showed signal reduction. After treatment, several brain regions also showed signal enhancement. Comparisons within the healthy control group also showed activation in multiple brain regions, including the lenticular nucleus, inferior frontal gyrus, and superior temporal gyrus, while in the experimental group, no signal changes were detected in these brain regions. At the same time, comparison of fMRI images of patients with intractable peripheral facial paralysis before and after treatment showed that the cerebellar amygdala, superior frontal gyrus, cerebellar mountaintop, and other brain areas were activated, and all showed positive activation. After treatment, the average House-Brackmann (H-B) and Sunnybrook scores of the experimental group were 3.82 and 51, respectively, and the change was significant compared with that before treatment (P < 0.05). In conclusion, the newly prepared 129Xe nanoprobe-based fMRI scan can reflect the functional changes of cerebral cortex after acupuncture. The acupuncture treatment may achieve its therapeutic effect by promoting the functional reorganization of the cerebral cortex in the treatment of intractable facial paralysis.


Assuntos
Terapia por Acupuntura , Paralisia Facial , Encéfalo/diagnóstico por imagem , Paralisia Facial/diagnóstico por imagem , Paralisia Facial/terapia , Humanos , Imageamento por Ressonância Magnética , Isótopos de Xenônio
13.
Brain Res Bull ; 183: 94-103, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35247488

RESUMO

High-frequency repetitive transcranial magnetic stimulation (rTMS) is a widely used and effective biological treatment for depression. Although previous studies have shown that astrocyte function may be modified by rTMS, the specific neurobiological mechanisms underlying its antidepressant action are not clear. Substantial evidence has accumulated indicating that neurotrophin dysfunction and neuronal apoptosis play a role in the development of depression. To evaluate this hypothesis, we applied a chronical unpredictable mild stress (CUMS) protocol to induce depression-like behaviors in rats, followed by the delivery of 10-Hz rTMS for 3 weeks. Behavioral outcome measures consisted of a sucrose preference test, forced swimming test, and open field test. Histological analysis focused on apoptosis, expression of GFAP and FGF2, and FGF2 pathway-related proteins. The results showed that after rTMS treatment, the rats' sucrose preference increased, open field performance improved while the immobility time of forced swimming decreased. The behavioral changes seen in rTMS treated rats were accompanied by marked reductions in the number of TUNEL-positive neural cells and the level of expression of BAX and by an increase in Bcl2. Furthermore, the expression of GFAP and FGF2 was increased, along with activation of FGF2 downstream pathway. These results suggest that rTMS treatment can improve depression-like behavior, attenuate neural apoptosis, and reverse reduction of astrocytes in a rat model of depression. We hypothesize that the therapeutic action of rTMS in CUMS-induced rats is linked to the activation of the FGF2/FGFR1/p-ERK signaling pathway.


Assuntos
Depressão , Estimulação Magnética Transcraniana , Animais , Depressão/metabolismo , Modelos Animais de Doenças , Fator 2 de Crescimento de Fibroblastos/metabolismo , Hipocampo/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Estresse Psicológico/metabolismo , Estimulação Magnética Transcraniana/métodos
14.
J Alzheimers Dis ; 87(1): 285-304, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35275533

RESUMO

BACKGROUND: Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) are neuropsychological tests commonly used by physicians for screening cognitive dysfunction of Alzheimer's disease (AD). Due to different imperfect reference standards, the performance of MoCA and MMSE do not reach consensus. It is necessary to evaluate the consistence and differentiation of MoCA and MMSE in the absence of a gold standard for AD. OBJECTIVE: We aimed to assess the accuracy of MoCA and MMSE in screening AD without a gold standard reference test. METHODS: Studies were identified from PubMed, Web of Science, CNKI, Chinese Wanfang Database, China Science and Technology Journal Database, and Cochrane Library. Our search was limited to studies published in English and Chinese before August 2021. A hierarchical Bayesian latent class model was performed in meta-analysis when the gold standard was absent. RESULTS: A total of 67 studies comprising 5,554 individuals evaluated for MoCA and 76,862 for MMSE were included in this meta-analysis. The pooled sensitivity was 0.934 (95% CI 0.905 to 0.954) for MoCA and 0.883 (95% CI 0.859 to 0.903) for MMSE, while the pooled specificity was 0.899 (95% CI 0.859 to 0.928) for MoCA and 0.903 (95% CI 0.879 to 0.923) for MMSE. MoCA was useful to rule out dementia associated with AD with lower negative likelihood ratio (LR-) (0.074, 95% CI 0.051 to 0.108). MoCA showed better performance with higher diagnostic odds ratio (DOR) (124.903, 95% CI 67.459 to 231.260). CONCLUSION: MoCA had better performance than MMSE in screening dementia associated with AD from patients with mild cognitive impairment or healthy controls.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Teorema de Bayes , Cognição , Disfunção Cognitiva/psicologia , Humanos , Testes de Estado Mental e Demência , Testes Neuropsicológicos
15.
Theranostics ; 12(5): 2266-2289, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265210

RESUMO

Rational: Intracellular bacterial survival is a major factor causing chronic or recurrent infection, leading to the failure of both host defense and/or antibiotic treatment. However, the elimination of intracellular bacteria is challenging as they are protected from antibiotics and host immune attack. Recent studies have indicated that iron helps macrophages against intracellular bacteria, contradictory to traditional "nutritional immunity", in which iron is considered a key nutrient for bacterial survival in host cells. However, how iron facilitates intracellular bacterial death has not been fully clarified. In this study, we found that ferroptotic stress can help macrophages suppress intracellular bacteria by reversing the importation of ferrous iron into bacterial vacuoles via ferroportin and thereby inducing in situ ferroptosis-like bacterial death. Methods: A macrophage model of bacterial invasion was established to monitor dynamic changes in ferroptotic hallmarks, including ferrous iron and lipid peroxidation. Ferroptosis inducers and inhibitors were added to the model to evaluate the relationship between ferroptotic stress and intracellular bacterial survival. We then determined the spatiotemporal distributions of ferroportin, ferrous iron, and lipid peroxidation in macrophages and intracellular bacteria. A bacterial infection mouse model was established to evaluate the therapeutic effects of drugs that regulate ferroptotic stress. Results: Ferrous iron and lipid peroxidation increased sharply in the early stage of bacterial infection in the macrophages, then decreased to normal levels in the late stage of infection. The addition of ferroptosis inducers (ras-selective lethal small molecule 3, sulfasalazine, and acetaminophen) in macrophages promoted intracellular bacterial suppression. Further studies revealed that ferrous iron could be delivered to the intracellular bacterial compartment via inward ferroportin transportation, where ferrous iron induced ferroptosis-like death of bacteria. In addition, ferroptotic stress declined to normal levels in the late stage of infection by regulating iron-related pathways in the macrophages. Importantly, we found that enhancing ferroptotic stress with a ferroptosis inducer (sulfasalazine) successfully suppressed bacteria in the mouse infection models. Conclusions: Our study suggests that the spatiotemporal response to ferroptosis stress is an efficient pathway for macrophage defense against bacterial invasion, and targeting ferroptosis may achieve therapeutic targets for infectious diseases challenged by intracellular pathogens.


Assuntos
Ferroptose , Sulfassalazina , Animais , Morte Celular , Ferro/metabolismo , Macrófagos/metabolismo , Camundongos , Sulfassalazina/farmacologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-35290577

RESUMO

Air pollution and ischemic stroke (IS) are both vital factors affecting the health of Beijing citizens. This study aims at exploring the associations between air pollution, meteorology, and the hospital admission of IS (IS HA). Information on 476,659 IS inpatients in secondary and higher hospitals in Beijing from 2013 to 2018 were collected. A time-stratified case-crossover design with the generalized additive model and the distributed lag nonlinear model were used. In the single-pollutant models, an inter-quartile range increase in O3, SO2, CO, and NO2 resulted in a significant highest increase in IS HA by 2.23% (95% CI: 1.56%, 2.90%), 1.53% (95% CI: 1.12%, 1.95%), 1.05% (95% CI: 0.70%, 1.40%), and 0.51% (95% CI: 0.24%, 0.79%) on the day of pollution, so did PM2.5 and PM10 by 1.13% (95% CI: 0.68%, 1.59%) and 1.19% (95% CI: 0.74%, 1.64%) at a lag of 0-5 days. There was a nonlinear relationship between meteorology and IS HA. In the multivariate model, the cumulative relative risks with a maximum lag time of 21 days of PM2.5 and NO2 were 1.11 (95% CI: 1.04, 1.19) and 0.88 (95% CI: 0.82, 0.94), while the effects of SO2, O3, and meteorology were insignificant. The findings suggested that particulate pollutants could increase the risk of IS, and the elderly were more sensitive to it, while the results of gaseous pollutants are still discordant. The control of air pollution and the protection of susceptible populations should receive higher attention from policymakers.

17.
Ann Transl Med ; 10(2): 29, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35282083

RESUMO

Background: Despite decades of research, no precise mechanisms of Alzheimer's disease (AD) development have been elucidated. This study aimed to investigate novel diagnostic biomarkers in both peripheral blood cells and hippocampus tissue, and the pathogenesis of memory impairment in AD. Methods: mRNA microarray data, including hippocampus samples (GSE1297 and GSE5281) and peripheral blood mononuclear cells (PBMCs) (GSE63060 and GSE63061), associated with AD were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between AD and normal-aging samples were screened through a comprehensive analysis of multiple gene expression spectra after gene reannotation and batch normalization. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were used to analyze hub genes and to discover potential biomarkers related to AD. Protein-protein interaction (PPI) network maps were constructed to visualize the correlation between possible genes. The CIBERSORT algorithm was built to explore the patterns of PBMC infiltration to investigate the role of inflammation in the pathogenesis of AD. Results: The bioinformatics analysis indicated 1,261 DEGs in the hippocampal samples and 290 in PBMCs when comparing patients with AD with normal-aging individuals. We selected 28 genes co-expressed in the hippocampus and PBMCs. A functional analysis of differential genes revealed that they were primarily involved in neuronal death, immune response, and mitochondrial function. Further, immune cell infiltration patterns demonstrated that the levels of naive CD4+ T cells, resting natural killer cells, M0 macrophages, and activated mast cells were higher in the peripheral blood of patients with AD, while resting memory CD4+ T cells were significantly lower. Conclusions: The key gene changes present in both the hippocampus and PBMCs highly suggest their utility as an AD biomarker. In addition, according to our present results, immune abnormalities may have an important role in AD pathophysiology. When patients display these peripheral blood immune abnormalities, they may be recognized as being at high risk of developing AD.

18.
Front Cardiovasc Med ; 9: 823381, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295269

RESUMO

Background: Acute myocardial infarction (AMI) is considered an acute coronary syndrome (ACS), which is caused by the death of myocardial cells after prolonged ischemia, and there is a high risk of sudden death during AMI. Therefore, the purpose of this study is to explore the relationship between thrombin activatable fibrinolysis inhibitor (TAFI) and AMI and provide evidence for their association and potentially the prevention of AMI. Methods: There were 228 subjects included in this retrospective study, which included 78 AMI patients and 150 controls. The immune turbidimetry was used to measure TAFI concentration in the serum. Mann-Whitney U test was used to compare serum TAFI levels. The logistic regression analysis was used to construct a model of influencing factors of AMI. The dose-response relationship between serum TAFI level and AMI was explored by using the restricted cubic spline (RCS) functions combined with logistic regression analysis. Results: The serum TAFI levels of the AMI group were higher than the control group's (P = 0.003). The risk of AMI in the high-TAFI level group was 2.24 times higher than the low-TAFI level group (P = 0.007) and it was 2.74 times higher after adjustment of other risk factors (P = 0.025). According to the dose-response curve, the risk of AMI increased significantly with an increase of serum TAFI concentration (P = 0.0387). Conclusion: Acute myocardial infarction patients had higher serum TAFI levels, and TAFI was an independent risk factor for AMI patients. Serum TAFI levels demonstrated a dose- dependent response to the risk of AMI. Our study provides evidence that TAFI could be used for risk stratification of AMI patients.

19.
Int J Endocrinol ; 2022: 2789279, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295847

RESUMO

Objective: To investigate the correlation between thyroid nodules and microalbuminuria in type 2 diabetic mellitus. Methods: A total of 270 patients with type 2 diabetes at Tongzhou Branch of Dongzhimen Hospital were enrolled in this retrospective study. Data were collected from the inpatient electronic files between January 2018 and January 2020. The laboratory indexes of the two groups (thyroid nodule group with 172 cases and control group including 98 cases without thyroid nodules) were statistically analyzed by binomial logistic regression analysis and Spearman correlation analysis. Results: The proportion of microalbuminuria (MAU) in the thyroid nodule group was larger than that in the control group. Age, serum TT4, and FT4 in the thyroid nodule group were significantly higher compared with the control group. The binary logistic regression analysis indicated that age, sex, FT4, and MAU were the risk factors for thyroid nodule in T2DM patients. Spearman correlation analysis showed that the thyroid nodule was significantly positively correlated with MAU, age, FT4, and TT4. Conclusions: MAU might be an independent risk factor for thyroid nodule in type 2 diabetic mellitus.

20.
J Orthop Surg Res ; 17(1): 159, 2022 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-35279159

RESUMO

BACKGROUND: Studies of aberrantly expressed circular RNAs (circRNAs) can provide insights into the molecular mechanisms of osteosarcoma (OS). However, the role of circ_0001174 in OS progression remains unknown. This study is aimed to identify differentially expressed circRNAs and messenger RNAs (mRNAs) in patients with OS and to investigate potential regulatory ways of circ_0001174. METHODS: High-throughput sequencing was performed to screen aberrantly expressed circRNAs and mRNAs between tumor and paracancerous tissues from patients with OS. Several bioinformatics tools were used to analyze the functions and pathways of the differentially expressed genes between the tissues. Cell counting kit-8, cell migration and invasion assays were performed to evaluate the functions of the critical circRNAs. RNA interference experiments, quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting were used to explore the relationship between miR-186-5p and circ_0001174 or metastasis-associated in colon cancer 1 (MACC1). RESULTS: Compared with the paracancerous tissues, 109 circRNAs and 1264 mRNAs were differentially expressed in the OS tissues, including 88 circRNAs and 707 mRNAs that were upregulated and 21 circRNAs and 557 mRNAs that were downregulated. The expression of four upregulated and four downregulated circRNAs was validated using RT-qPCR; the results were consistent with the sequencing data, and circ_0001174 was found to be significantly upregulated in 16 pairs of OS tissues and OS cell lines (fold change > 2.0, P value < 0.05). Knockdown of circ_0001174 inhibited the proliferation, migration, and invasion of OS cells. Additionally, circ_0001174 directly and negatively modulated the expression of miR-186-5p and positively regulated the expression of MACC1. CONCLUSIONS: Abnormally high expression of circ_0001174 may promote the proliferation, migration, and invasion of OS cells through up-regulating MACC1 by sponging miR-186-5p. These results provide insight into therapeutic targets for preventing and treating OS.


Assuntos
Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Proliferação de Células/genética , MicroRNAs/genética , Osteossarcoma/genética , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Humanos , MicroRNAs/metabolismo , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Reação em Cadeia da Polimerase em Tempo Real , Transativadores
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