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1.
Bioinformatics ; 39(12)2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37995293

RESUMO

SUMMARY: A variety of computational methods have been developed to identify functionally related gene modules from genome-wide gene expression profiles. Integrating the results of these methods to identify consensus modules is a promising approach to produce more accurate and robust results. In this application note, we introduce COMMO, the first web server to identify and analyze consensus gene functionally related gene modules from different module detection methods. First, COMMO implements eight state-of-the-art module detection methods and two consensus clustering algorithms. Second, COMMO provides users with mRNA and protein expression data for 33 cancer types from three public databases. Users can also upload their own data for module detection. Third, users can perform functional enrichment and two types of survival analyses on the observed gene modules. Finally, COMMO provides interactive, customizable visualizations and exportable results. With its extensive analysis and interactive capabilities, COMMO offers a user-friendly solution for conducting module-based precision medicine research. AVAILABILITY AND IMPLEMENTATION: COMMO web is available at https://commo.ncpsb.org.cn/, with the source code available on GitHub: https://github.com/Song-xinyu/COMMO/tree/master.


Assuntos
Redes Reguladoras de Genes , Software , Consenso , Algoritmos , Computadores
2.
J Nanobiotechnology ; 22(1): 315, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840207

RESUMO

Chronic hepatitis B poses a significant global burden, modulating immune cells, leading to chronic inflammation and long-term damage. Due to its hepatotropism, the hepatitis B virus (HBV) cannot infect other cells. The mechanisms underlying the intercellular communication among different liver cells in HBV-infected individuals and the immune microenvironment imbalance remain elusive. Exosomes, as important intercellular communication and cargo transportation tools between HBV-infected hepatocytes and immune cells, have been shown to assist in HBV cargo transportation and regulate the immune microenvironment. However, the role of exosomes in hepatitis B has only gradually received attention in recent years. Minimal literature has systematically elaborated on the role of exosomes in reshaping the immune microenvironment of the liver. This review unfolds sequentially based on the biological processes of exosomes: exosomes' biogenesis, release, transport, uptake by recipient cells, and their impact on recipient cells. We delineate how HBV influences the biogenesis of exosomes, utilizing exosomal covert transmission, and reshapes the hepatic immune microenvironment. And based on the characteristics and functions of exosomes, potential applications of exosomes in hepatitis B are summarized and predicted.


Assuntos
Exossomos , Vírus da Hepatite B , Hepatite B Crônica , Hepatócitos , Fígado , Exossomos/imunologia , Exossomos/metabolismo , Humanos , Vírus da Hepatite B/imunologia , Fígado/imunologia , Fígado/virologia , Animais , Hepatite B Crônica/imunologia , Hepatócitos/virologia , Hepatócitos/imunologia , Comunicação Celular , Microambiente Celular/imunologia , Hepatite B/imunologia , Hepatite B/virologia
3.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34556577

RESUMO

Proteins achieve efficient energy storage and conversion through electron transfer along a series of redox cofactors. Multiheme cytochromes are notable examples. These proteins transfer electrons over distance scales of several nanometers to >10 µm and in so doing they couple cellular metabolism with extracellular redox partners including electrodes. Here, we report pump-probe spectroscopy that provides a direct measure of the intrinsic rates of heme-heme electron transfer in this fascinating class of proteins. Our study took advantage of a spectrally unique His/Met-ligated heme introduced at a defined site within the decaheme extracellular MtrC protein of Shewanella oneidensis We observed rates of heme-to-heme electron transfer on the order of 109 s-1 (3.7 to 4.3 Å edge-to-edge distance), in good agreement with predictions based on density functional and molecular dynamics calculations. These rates are among the highest reported for ground-state electron transfer in biology. Yet, some fall 2 to 3 orders of magnitude below the Moser-Dutton ruler because electron transfer at these short distances is through space and therefore associated with a higher tunneling barrier than the through-protein tunneling scenario that is usual at longer distances. Moreover, we show that the His/Met-ligated heme creates an electron sink that stabilizes the charge separated state on the 100-µs time scale. This feature could be exploited in future designs of multiheme cytochromes as components of versatile photosynthetic biohybrid assemblies.


Assuntos
Grupo dos Citocromos c/metabolismo , Citocromos/metabolismo , Elétrons , Heme/metabolismo , Histidina/metabolismo , Metionina/metabolismo , Shewanella/metabolismo , Grupo dos Citocromos c/química , Citocromos/química , Transporte de Elétrons , Heme/química , Histidina/química , Metionina/química , Simulação de Dinâmica Molecular , Nanofios , Oxirredução
4.
Angew Chem Int Ed Engl ; 63(11): e202319896, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38197522

RESUMO

Upgrading of polyethylene terephthalate (PET) waste into valuable oxygenated molecules is a fascinating process, yet it remains challenging. Herein, we developed a two-step strategy involving methanolysis of PET to dimethyl terephthalate (DMT), followed by hydrogenation of DMT to produce the high-valued chemical methyl p-methyl benzoate (MMB) using a fixed-bed reactor and a Cu/ZrO2 catalyst. Interestingly, we discovered the phase structure of ZrO2 significantly regulates the selectivity of products. Cu supported on monoclinic ZrO2 (5 %Cu/m-ZrO2 ) exhibits an exceptional selectivity of 86 % for conversion of DMT to MMB, while Cu supported on tetragonal ZrO2 (5 %Cu/t-ZrO2 ) predominantly produces p-xylene (PX) with selectivity of 75 %. The superior selectivity of MMB over Cu/m-ZrO2 can be attributed to the weaker acid sites present on m-ZrO2 compared to t-ZrO2 . This weak acidity of m-ZrO2 leads to a moderate adsorption capability of MMB, and facilitating its desorption. Furthermore, DFT calculations reveal Cu/m-ZrO2 catalyst shows a higher effective energy barrier for cleavage of second C-O bond compared to Cu/t-ZrO2 catalyst; this distinction ensures the high selectivity of MMB. This catalyst not only presents an approach for upgrading of PET waste into fine chemicals but also offers a strategy for controlling the primary product in a multistep hydrogenation reaction.

5.
J Transl Med ; 21(1): 916, 2023 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-38105228

RESUMO

Mounting attention has been focused on defects of the autophagy-lysosomal pathway in sepsis, however, the precise mechanisms governing the autophagy-lysosomal process in sepsis are poorly known. We have previously reported that Erbin deficiency aggravated the inflammatory response and organ injuries caused by sepsis. In the present study, we found that Erbin knockout impaired the autophagy process in both muramyl dipeptide (MDP)-induced bone marrow-derived macrophages (BMDMs) and sepsis mouse liver and lung, as detected by the accumulation of LC3-II and SQSTM1/p62, and autophagosomes. Pretreatment with autophagy inhibitor chloroquine (CQ) further aggravated inflammatory response and organ injuries in vivo and in vitro sepsis model. We also observed that the impaired lysosomal function mediated autophagic blockade, as detected by the decreased expression of ATP6V, cathepsin B (CTSB) and LAMP2 protein. Immunoprecipitation revealed that the C-terminal of Erbin (aa 391-964) interacts with the N-terminal of transcription factor EB (TFEB) (aa 1-247), and affects the stability of TFEB-14-3-3 and TFEB-PPP3CB complexes and the phosphorylation status of TFEB, thereby promote the nucleus translocation of TFEB and the TFEB target genes transcription. Thus, our study suggested that Erbin alleviated sepsis-induced inflammatory responses and organ injuries by rescuing dysfunction of the autophagy-lysosomal pathway through TFEB-14-3-3 and TFEB-PPP3CB pathway.


Assuntos
Núcleo Celular , Peptídeos e Proteínas de Sinalização Intracelular , Sepse , Animais , Camundongos , Autofagossomos/metabolismo , Autofagia/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Núcleo Celular/metabolismo , Inflamação/etiologia , Inflamação/genética , Inflamação/metabolismo , Lisossomos/genética , Lisossomos/metabolismo , Sepse/complicações , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
6.
Crit Rev Food Sci Nutr ; : 1-12, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37218681

RESUMO

Several epidemiological studies have investigated the association between sugar intake, the levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the risk of hypertension, but findings have been inconsistent. We carried out a systematic review and meta-analysis of observational studies to examine the associations between sugar intake, hypertension risk, and BP levels. Articles published up to February 2, 2021 were sourced through PubMed, EMBASE and Web of Science. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a fixed- or random-effects model. Restricted cubic splines were used to evaluate dose-response associations. Overall, 35 studies were included in the present meta-analysis (23 for hypertension and 12 for BP). Sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) were positively associated with hypertension risk: 1.26 (95% CI, 1.15-1.37) and 1.10 (1.07-1.13) per 250-g/day increment, respectively. For SBP, only SSBs were significant with a pooled ß value of 0.24 mmHg (95% CI, 0.12-0.36) per 250 g increase. Fructose, sucrose, and added sugar, however, were shown to be associated with elevated DBP with 0.83 mmHg (0.07-1.59), 1.10 mmHg (0.12-2.08), and 5.15 mmHg (0.09-10.21), respectively. Current evidence supports the harmful effects of sugar intake for hypertension and BP level, especially SSBs, ASBs, and total sugar intake.

7.
J Chem Phys ; 159(16)2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37902224

RESUMO

Ligand-decorated metal surfaces play a pivotal role in various areas of chemistry, particularly in selective catalysis. Molecular dynamics simulations at the molecular mechanics level of theory are best adapted to gain complementary insights to experiments regarding the structure and dynamics of such organic films. However, standard force fields tend to capture only weak physisorption interactions. This is inadequate for ligands that are strongly adsorbed such as carboxylates on metal surfaces. To address this limitation, we employ the Gaussian Lennard-Jones (GLJ) potential, which incorporates an attractive Gaussian potential between the surface and ligand atoms. Here, we develop this approach for the interaction between cobalt surfaces and carboxylate ligands. The accuracy of the GLJ approach is validated through the analysis of the interaction of oxygen with two distinct cobalt surfaces. The accuracy of this method reaches a root mean square deviation (RMSD) of about 3 kcal/mol across all probed configurations, which corresponds to a percentage error of roughly 4%. Application of the GLJ force field to the dynamics of the organic layer on these surfaces reveals how the ligand concentration influences the film order, and highlights differing mobility in the x and y directions, attributable to surface corrugation on Co(112̄0). GLJ is versatile, suitable for a broad range of metal/ligand systems, and can, subsequently, be utilized to study the organic film on the adsorption/desorption of reactants and products during a catalytic process.

8.
Acta Radiol ; 64(2): 798-805, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35306860

RESUMO

BACKGROUND: Coronary artery distension and aneurysm are complications of Kawasaki disease in children. PURPOSE: To develop a Z-score regression model for coronary artery diameter in children that could be used as reference. MATERIAL AND METHODS: This retrospective analysis included children with normal heart structure between March 2013 and April 2017. Body surface area (BSA) was calculated. The diameters of the right coronary, left main coronary, left anterior descending, and circumflex arteries were measured by echocardiography. Pearson correlation analysis was used to establish linear, exponential, logarithmic, power, and square root regression models. RESULTS: The analysis included 509 children (280 boys) aged 1 day to 15.2 years. Coronary artery diameters were significantly correlated with age, height, body mass, BSA, and BSA (r = 0.663-0.826; P < 0.05), with a stronger correlation for BSA than BSA (P < 0.05). The adjusted determination coefficients (Ra2) were higher for the exponential and square root models than for the other models (P < 0.05). The random error term variance was constant for the exponential model (P > 0.05), and processing with the weighted least-square methods eliminated heteroscedasticity in the other models. The Z-scores were normally distributed for the exponential and square root models (P > 0.05). CONCLUSION: Overall, the square root model was the optimal equation for the calculation of coronary artery Z-score in Chinese Han children. This model could be used to facilitate the diagnosis of coronary artery distension in children with suspected Kawasaki disease.


Assuntos
Vasos Coronários , Síndrome de Linfonodos Mucocutâneos , Criança , Humanos , Lactente , Masculino , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/anatomia & histologia , População do Leste Asiático , Ecocardiografia/métodos , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico por imagem , Estudos Retrospectivos , Feminino , Recém-Nascido , Pré-Escolar , Adolescente
9.
Ren Fail ; 45(1): 2199097, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37051667

RESUMO

OBJECTIVES: The objective of this study was to develop clinical scores to predict the risk of intensive care unit (ICU) admission in patients with COVID-19 and end stage kidney disease (ESKD). METHODS: This was a prospective study in which 100 patients with ESKD were enrolled and divided into two groups: the ICU group and the non-ICU group. We utilized univariate logistic regression and nonparametric statistics to analyze the clinical characteristics and liver function changes of both groups. By plotting receiver operating characteristic curves, we identified clinical scores that could predict the risk of ICU admission. RESULTS: Out of the 100 patients with Omicron infection, 12 patients were transferred to the ICU due to disease aggravation, with an average of 9.08 days from hospitalization to ICU transfer. Patients transferred to the ICU more commonly experienced shortness of breath, orthopnea, and gastrointestinal bleeding. The peak liver function and changes from baseline in the ICU group were significantly higher, with p values <.05. We found that the baseline platelet-albumin-bilirubin score (PALBI) and neutrophil-to-lymphocyte ratio (NLR) were good predictors of ICU admission risk, with area under curve values of 0.713 and 0.770, respectively. These scores were comparable to the classic Acute Physiology and Chronic Health Evaluation II (APACHE-II) score (p > .05). CONCLUSION: Patients with ESKD and Omicron infection who are transferred to the ICU are more likely to have abnormal liver function. The baseline PALBI and NLR scores can better predict the risk of clinical deterioration and early transfer to the ICU for treatment.


Assuntos
COVID-19 , Falência Renal Crônica , Humanos , Estudos Prospectivos , Neutrófilos , COVID-19/complicações , SARS-CoV-2 , Hospitalização , Linfócitos , Unidades de Terapia Intensiva , Falência Renal Crônica/terapia , Albuminas , Curva ROC , Prognóstico , Estudos Retrospectivos
10.
Int J Mol Sci ; 24(4)2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36834536

RESUMO

Dermal papilla cells (DPCs) play important roles in hair growth regulation. However, strategies to regrow hair are lacking. Here, global proteomic profiling identified the tetrathiomolybdate (TM)-mediated inactivation of copper (Cu) depletion-dependent mitochondrial cytochrome c oxidase (COX) as the primary metabolic defect in DPCs, leading to decreased Adenosine Triphosphate (ATP) production, mitochondrial membrane potential depolarization, increased total cellular reactive oxygen species (ROS) levels, and reduced expression of the key marker of hair growth in DPCs. By using several known mitochondrial inhibitors, we found that excessive ROS production was responsible for the impairment of DPC function. We therefore subsequently showed that two ROS scavengers, N-acetyl cysteine (NAC) and ascorbic acid (AA), partially prevented the TM- and ROS-mediated inhibition of alkaline phosphatase (ALP). Overall, these findings established a direct link between Cu and the key marker of DPCs, whereby copper depletion strongly impaired the key marker of hair growth in the DPCs by increasing excessive ROS production.


Assuntos
Derme , Folículo Piloso , Folículo Piloso/metabolismo , Células Cultivadas , Fosfatase Alcalina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteômica , Cobre/metabolismo , Proliferação de Células
11.
Toxicol Mech Methods ; 33(8): 656-666, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37434431

RESUMO

BACKGROUND: Aquilaria sinensis (Lour.) Gilg (ASG) has been used as traditional medicine for centuries. However, the active ingredients from leaves and their anti-inflammatory mechanism are rarely reported. The network pharmacology and molecular docking strategies were applied to explore the potential mechanisms of Benzophenone compounds from the leaves of ASG (BLASG) against inflammation. METHODS: BLASG-related targets were obtained from the SwissTargetPrediction and PharmMapper databases. Inflammation-associated targets were retrieved from GeneGards, DisGeNET, and CTD databases. Cytoscape software was used to draw a network diagram of BLASG and its corresponding targets. DAVID database was applied for enrichment analyses. A protein-protein interaction (PPI) network was constructed to identify the hub targets of BLASG. Molecular docking analyses were performed by AutoDockTools 1.5.6. Moreover, we used ELISA and qRT-PCR assays to validate the anti-inflammatory effects of BLASG by cell experiments. RESULTS: Four BLASG were extracted from ASG, and corresponding 225 potential targets were identified. PPI network analysis indicated that SRC, PIK3R1, AKT1, and other targets were the core therapeutic targets. Enrichment analyses revealed that the effects of BLASG are regulated by targets associated with apoptosis and inflammation-related pathways. In addition, molecular docking revealed that BLASG combined well with PI3K and AKT1. Furthermore, BLASG significantly decreased the inflammatory cytokines levels and down-regulated PIK3R1 and AKT1 gene expression in RAW264.7 cells. CONCLUSION: Our study predicted the potential targets and pathways of BLASG against inflammation, which offered a promising strategy to reveal the therapeutic mechanism of natural active components in the treatment of diseases.


Assuntos
Medicamentos de Ervas Chinesas , Thymelaeaceae , Simulação de Acoplamento Molecular , Farmacologia em Rede , Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Folhas de Planta , Benzofenonas/farmacologia
12.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-37987034

RESUMO

Preimplantation genetic testing is an important part in assisted reproductive technology, which can block the intergenerational inheritance of single gene or chromosomal diseases. Preimplantation genetic testing for polygenic disease risk (PGT-P) is the latest development in the field. It is known that polygenic diseases usually have the characteristics of high incidence, late onset, affecting the quality of life and mental health of patients. On the basis of the development of artificial intelligence and genetic detection technology, PGT-P can analyze genetic material, calculate polygenic risk score turning into incidence probability. Embryos with relatively low incidence probability can be screened for transfer, so as to reduce the possibility of offspring suffering from the disease in the future, which has significant clinical and social significance. At present, PGT-P has been applied clinically and made phased progress at home and abroad. At the same time, as a developing technology, PGT-P still has some technical defects, unstable results, environmental influences and racial differences cannot be ruled out. From the perspective of ethics, if the screening indications are not strictly regulated, it is likely to cause new social problems. In this paper, we review the technical composition and recent progress of PGT-P, and put forward the prospect of its future development, especially how to establish a complete and suitable screening model for Chinese population.

13.
J Neurosci ; 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34035138

RESUMO

Diverse functions such as decision-making and memory consolidation may depend upon communication between neurons in hippocampus (HP) and prefrontal cortex (PFC). HP replay is a candidate mechanism to facilitate this communication, however details remain largely unknown due to the technical challenges of recording sufficient numbers of HP neurons for replay while also recording PFC neurons. Here we implanted male rats with 40-tetrode drives, split between HP and PFC, during learning of a Y-maze spatial memory task. Surprisingly, we found that in contrast to their non-selectivity for maze arm during movement, a portion of PFC neurons were highly selective for HP replay of different arms. Moreover, PFC neurons' selectivity to HP non-local arm representation during running tended to match their replay arm selectivity and was predictive of future choice. Thus, PFC activity that is tuned to HP activity is best explained by non-local HP position representations rather than HP representation of actual position, providing a new potential mechanism of HP-PFC coordination during HP replay.SIGNIFICANCE STATEMENTThe hippocampus is implicated in spatial learning while the prefrontal cortex is implicated in decision-making. The question of how the two areas interact has been of great interest. A specific activity type in hippocampus called replay is particularly interesting because it resembles internal exploration of non-local experiences, but is technically challenging to study, requiring recordings from large numbers of hippocampus neurons simultaneously. Here we combined replay recordings from hippocampus with prefrontal recordings, to reveal a surprising degree of selectivity for replay, and a pattern of coordination that supports some conceptions of hippocampocortical interaction and challenges others.

14.
BMC Genomics ; 23(1): 847, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36544082

RESUMO

BACKGROUND: Toxocara canis is distributed worldwide, posing a serious threat to both human and dog health; however, the pathogenesis of T. canis infection in dogs remains unclear. In this study, the changes in microRNA (miRNA) expression profiles in the bone marrow of Beagle dogs were investigated by RNA-seq and bioinformatics analysis. RESULTS: Thirty-nine differentially expressed (DE) miRNAs (DEmiRNAs) were identified in this study. Among these, four DEmiRNAs were identified at 24 h post-infection (hpi) and all were up-regulated; eight DEmiRNAs were identified with two up-regulated miRNAs and six down-regulated miRNAs at 96 hpi; 27 DEmiRNAs were identified with 13 up-regulated miRNAs and 14 down-regulated miRNAs at 36 days post-infection (dpi). Among these DEmiRNAs, cfa-miR-193b participates in the immune response by regulating the target gene cd22 at 24 hpi. The novel_328 could participate in the inflammatory and immune responses through regulating the target genes tgfb1 and tespa1, enhancing the immune response of the host and inhibiting the infection of T. canis at 96 hpi. In addition, cfa-miR-331 and novel_129 were associated with immune response and self-protection mechanisms at 36 dpi. 20 pathways were significantly enriched by KEGG pathway analysis, most of which were related to inflammatory response, immune response and cell differentiation, such as Cell adhesion molecules (CAMs), ECM-receptor interaction and Focal adhesion. CONCLUSIONS: These findings suggested that miRNAs of Beagle dog bone marrow play important roles in the pathogenesis of T. canis infection in dogs and provided useful resources to better understand the interaction between T. canis and the hosts.


Assuntos
MicroRNAs , Toxocaríase , Animais , Cães , Medula Óssea/metabolismo , Medula Óssea/parasitologia , Doenças do Cão/genética , Doenças do Cão/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Toxocara canis/genética , Toxocaríase/genética , Toxocaríase/metabolismo
15.
J Neuroinflammation ; 19(1): 237, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36171629

RESUMO

BACKGROUND: Microglia pyroptosis-mediated neuroinflammation is thought to be the crucial pathogenesis of sepsis-associated encephalopathy (SAE). Erbin has been reported to be associated with various inflammatory diseases. However, the role of Erbin in SAE and the relationship between Erbin and microglia pyroptosis are unknown. In this study, we investigated the promising role and underlying molecular mechanism of Erbin in the regulation of microglia pyroptosis. METHODS: WT and Erbin knockout mice underwent cecum ligation perforation (CLP) to induce SAE. Primary mouse microglia and BV2 cells were treated with LPS/nigericin in vitro. Behavioral tests were performed to evaluate cognitive function. Nissl staining and transmission electron microscopy were used to assess histological and structural lesions. ELISA and qPCR were carried out to detect neuroinflammation. Western blot and immunofluorescence were used to analyze protein expression. Flow cytometry and confocal microscopy were utilized to observe the Ca2+ changes in the cytoplasm and endoplasmic reticulum (ER). To further explore the underlying mechanism, STF083010 was administered to block the IRE1α/Xbp1s pathway. RESULTS: Erbin deletion resulted in more pronounced neuronal damage and cognitive impairment in mice that underwent CLP. Erbin knockout promoted microglial pyroptosis and inflammatory cytokines secretion in vivo and in vitro, which was mediated by activation of the IRE1α/Xbp1s. Treatment with the selective inhibitor STF083010 significantly inhibited IRE1α/Xbp1s pathway activity, decreased intracytoplasmic Ca2+, attenuated microglial pyroptosis, reduced pro-inflammatory cytokine secretion, lessened neuronal damage, and improved cognitive function. CONCLUSIONS: In SAE, Erbin inhibits IRE1/Xbp1s pathway activity and reduces the ER Ca2+ influx to the cytoplasm, reducing microglial pyroptosis.


Assuntos
Encefalopatia Associada a Sepse , Animais , Citocinas/metabolismo , Endorribonucleases , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Knockout , Microglia/metabolismo , Nigericina , Proteínas Serina-Treonina Quinases/genética , Piroptose/fisiologia , Encefalopatia Associada a Sepse/metabolismo , Sulfonamidas , Tiofenos
16.
Cancer Cell Int ; 22(1): 84, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35172823

RESUMO

PURPOSES: In addition to its role in cellular progression and cancer, SIRT6, a member of nicotinamide adenine dinucleotide (NAD+)-dependent class III deacylase sirtuin family, serves a variety of roles in the body's immune system. In this study, we sought to determine the relationship between the expression of SIRT6 and the clinicopathological outcomes of patients with solid tumours by conducting a meta-analysis of the available data. METHODS: The databases PubMed and ISI Web of Science were searched for relevant literature, and the results were presented here. Using Stata16.0, a meta-analysis was conducted to determine the impact of SIRT6 on clinicopathological characteristics and prognosis in malignancy patients. The results were published in the journal Cancer Research. The dataset from the Cancer Genome Atlas (TCGA) was used to investigate the prognostic significance of SIRT6 in various types of tumors. RESULTS: The inclusion and exclusion criteria were met by 15 studies. In patients with solid tumours, reduced SIRT6 expression was found to be related with improved overall survival (OS) (HR = 0.66, 95% CI = 0.45-0.97, P < 0.001) as well as improved disease-free survival (DFS) (HR = 0.48, 95% CI = 0.26-0.91, P < 0.001). Low SIRT6 expression was found to be associated with a better OS in breast cancer (HR = 0.49, 95% CI = 0.27-0.89, P = 0.179), but was found to be associated with a worse OS in gastrointestinal cancer (gastric cancer and colon cancer) (HR = 1.83, 95% CI = 1.20-2.79, P = 0.939) after subgroup analysis. In terms of clinicopathological characteristics, SIRT6 expression was found to be linked with distant metastasis (OR = 2.98, 95% CI = 1.59-5.57, P = 0.694). When the data from the TCGA dataset was compared to normal tissue, it was discovered that SIRT6 expression was significantly different in 11 different types of cancers. Meanwhile, reduced SIRT6 expression was shown to be associated with improved OS (P < 0.05), which was consistent with the findings of the meta-analysis. Aside from that, the expression of SIRT6 was found to be associated with both gender and clinical stage. CONCLUSION: The overall data of the present meta-analysis indicated that low expression of SIRT6 may predict a favorable survival for patients with solid tumors.

17.
BMC Geriatr ; 22(1): 905, 2022 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434542

RESUMO

BACKGROUND: As a result of the high prevalence of dysphagia in aged care facilities, demand for pureed diets is increasing. One of the biggest challenges for pureed diets is the reduced nutritional density due to the cooking process, such as when blending or softening with liquid. This study aimed to investigate the impact of innovative energy and protein-enriched meat puree on the nutrition intake and nutritional status of aged care residents requiring pureed diets. METHODS: This is a single-blinded randomised controlled trial conducted in two aged care facilities using a crossover design. Twenty-two residents aged 83.2 ± 7.3 years participated in a 12-week study. Participants were blocked randomised into two groups and received a 6-week of either control (unaltered freshly made pureed diets by facilities) or intervention diet, followed by a 2-week washout and then 6-week of alternative treatment. During the intervention, freshly made meat pureed portions were swapped to hydrolysed meat, which contained 144 -392 kcal and 5.6-6.8 g more energy and protein per 100 g. Nutrition intake was collected using a validated visual estimation method over 24 h on two non-consecutive days during the control and intervention phases. A two-tailed t-test was used to compare the significance. RESULTS: The intervention diet significantly increased energy (147 ± 285 kcal, p = .02), protein (4 ± 7 g, p = .04), and fat (3 ± 8 g, p = .07) intake in comparison to the control diet. Nutritional status was improved by the end of the intervention as evidenced by a higher nutritional assessment score using Mini-Nutritional Assessment - Short Form (9.1 ± 1.8) and a weight gain of 1.3 ± 1.7 g, p = .04. No significant differences were found in body composition using bioelectrical impedance analysis, calf circumference and mid-upper arm circumference. Though handgrip strength did not differ at the end of control and intervention, significance was found between the changes in control and intervention period. Plasma branched-chain amino acid increased significantly with hydrolysed meat consumption. CONCLUSIONS: As a dietary enrichment, hydrolysed meat is a promising intervention for pureed diet consumers in aged care facilities, improving residents' dietary intake and reducing malnutrition risk. Future larger multicentre studies with longer intervention periods are required to confirm the effectiveness and residents' acceptance. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12622000888763).


Assuntos
Força da Mão , Estado Nutricional , Humanos , Estudos Cross-Over , Ingestão de Energia , Austrália , Ingestão de Alimentos , Carne , Dieta
18.
BMC Pulm Med ; 22(1): 370, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36171599

RESUMO

BACKGROUND: There were relatively few studies about the incidence and risk factors for bloodstream infection (BSI) in patients with severe acute respiratory distress syndrome (ARDS) supported by veno-venous extracorporeal membrane oxygenation (VV-ECMO). METHODS: Patients who were diagnosed with severe ARDS and received VV-ECMO treatment in the medical intensive care unit of China-Japan Friendship Hospital from August 2013 to March 2019 were retrospectively studied. The pathogens isolated from blood culture (BC) were identified and analyzed for drug sensitivity. The risk factors for BSI were analyzed by logistic regression. RESULTS: A total of 105 patients were included in this single-center retrospective cohort study. Among them, 23 patients (22%) had BSIs. 19 cases were identified as primary BSI; while the other 4 cases were as secondary BSI. A total of 23 pathogenic strains were isolated from BCs, including gram-negative (G-) bacilli in 21 (91%) cases, gram-positive (G+) cocci in 1 case, fungus in 1 case, and multidrug-resistant (MDR) organisms in 8 cases. Compared with patients without BSI, patients with BSI had a higher Murray score (odds ratio = 6.29, P = 0.01) and more blood transfusion (odds ratio = 1.27, P = 0.03) during ECMO. CONCLUSIONS: The incidence of BSI in patients with severe ARDS supported by VV-ECMO was 22%. G- bacilli was the main pathogen, and most of them were MDR-G- bacilli (MDR-GNB). Higher Murray score and more blood transfusion may be the independent risk factors for BSI.


Assuntos
Oxigenação por Membrana Extracorpórea , Síndrome do Desconforto Respiratório , Sepse , Oxigenação por Membrana Extracorpórea/efeitos adversos , Humanos , Síndrome do Desconforto Respiratório/epidemiologia , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos , Fatores de Risco , Sepse/etiologia
19.
BMC Pulm Med ; 22(1): 177, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35509092

RESUMO

BACKGROUND: In patients with acute hypoxemic respiratory failure whose diagnosis is not established after initial evaluation, obtaining a histopathological diagnosis may improve the patients' prognosis. This study aims to compare the safety profile and diagnostic yields between transbronchial lung biopsy (TBLB) and transbronchial lung cryobiopsy (TBLC) in these patients. METHODS: A retrospective comparative study was conducted in a 26-bed intensive care unit over a 5-year period. The consecutive patients with acute hypoxemic respiratory failure who underwent TBLB or TBLC were included to determine the potential etiology. Patients characteristics, procedure related complications, pathological and multidisciplinary discussion (MDD) diagnostic yields, treatment modification and 28-day survival were analyzed. Prognostic factors were identified by Cox regression analysis. RESULTS: Forty-five and 25 consecutive patients underwent TBLB and TBLC, respectively. The patients underwent TBLC were more critical. There was no significant difference in overall procedure related complications of patients underwent TBLB and TBLC [15.6% (7/45) vs 28.0% (7/25), p = 0.212]. The rate of pathological diagnostic yield [72.0% (18/25) vs 37.8% (17/45), p = 0.006], MDD diagnostic yield [84.0% (21/25) vs 55.6% (25/45), p = 0.016] and subsequent treatment modification [84.0% (21/25) vs 57.8% (26/45), p = 0.025] in patients underwent TBLC were significantly higher than those in patients underwent TBLB. Multivariate analysis revealed that MDD diagnosis [HR 0.193 (95% CI 0.047-0.792), p = 0.022] and treatment modification [HR 0.204 (95% CI 0.065-0.638), p = 0.006] may be prognostic protective factors. CONCLUSIONS: TBLC can lead to an increased chance of establishing a diagnosis, which could significantly improve the patients' prognosis, with an acceptable safety profile.


Assuntos
Doenças Pulmonares Intersticiais , Insuficiência Respiratória , Biópsia/métodos , Broncoscopia/efeitos adversos , Broncoscopia/métodos , Estado Terminal , Humanos , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico , Insuficiência Respiratória/etiologia , Estudos Retrospectivos
20.
Dysphagia ; 37(5): 1314-1325, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-34993611

RESUMO

Texture-modified diets (TMDs) are commonly prescribed for older adults with swallowing difficulties to improve swallowing safety. The International Dysphagia Diet Standardization Initiative (IDDSI) provides a framework for terminology, definitions and testing of TMDs. This observational mixed-method study used the consolidated framework for implementation research (CFIR) to establish the barriers and enablers to IDDSI adoption in aged-care facilities (ACFs). Five New Zealand ACFs who had adopted IDDSI > 12 months previously were recruited. Evaluation tools were developed based on CFIR constructs, integrating data from (i) mealtime observations; (ii) manager interviews and (iii) staff (nursing, carers and kitchen) self-administrated surveys. All facility and kitchen managers were IDDSI aware and had access to online resources. Three sites had changed to commercially compliant products post-IDDSI adoption, which had cost implications. Awareness of IDDSI amongst staff ranged from 5 to 79% and < 50% of staff surveyed felt sufficiently trained. Awareness was greater in large sites and where IDDSI was mandated by head office. Managers had not mandated auditing and they felt this had led to reduced perceived importance. Managers felt staff required more training and staff wanted more training, believing it would improve food safety and quality of care. Lack of a dedicated project leader and no speech pathologist on-site were perceived barriers. Collaboration between healthcare assistants, kitchen staff and allied health assisted implementation. ACF staff were aware of IDDSI but staff awareness was low. Using the CFIR, site specific and generic barriers and enablers were identified to improve future implementation effectiveness. Managers and staff want access to regular training. Multidisciplinary collaboration and improving communication are essential. ACFs should consider TMD auditing regularly. Successful implementation of IDDSI allows improvement of quality of care and patient safety but requires a systematic, site-specific implementation plan.


Assuntos
Transtornos de Deglutição , Idoso , Deglutição , Dieta , Humanos , Refeições , Padrões de Referência
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