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1.
Int J Mol Sci ; 25(7)2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38612430

RESUMO

A variety of neurological and psychiatric disorders have recently been shown to be highly associated with the abnormal development and function of oligodendrocytes (OLs) and interneurons. OLs are the myelin-forming cells in the central nervous system (CNS), while interneurons are important neural types gating the function of excitatory neurons. These two types of cells are of great significance for the establishment and function of neural circuits, and they share similar developmental origins and transcriptional architectures, and interact with each other in multiple ways during development. In this review, we compare the similarities and differences in these two cell types, providing an important reference and further revealing the pathogenesis of related brain disorders.


Assuntos
Interneurônios , Oligodendroglia , Humanos , Bainha de Mielina , Neurônios , Encéfalo
2.
Adv Sci (Weinh) ; : e2306498, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38476116

RESUMO

Ca2+ signaling is essential for oligodendrocyte (OL) development and myelin formation. Inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) is an endoplasmic reticulum calcium channel and shows stage-dependent high levels in postmitotic oligodendrocyte precursor cells (OPCs). The role and potential mechanism of ITPR2 in OLs remain unclear. In this study, it is revealed that loss of Itpr2 in OLs disturbs Ca2+ homeostasis and inhibits myelination in adolescent mice. Animals with OL-specific deletion of Itpr2 exhibit anxiety/depressive-like behaviors and manifest with interrupted OPC proliferation, leading to fewer mature OLs in the brain. Detailed transcriptome profiling and signal pathway analysis suggest that MAPK/ERK-CDK6/cyclin D1 axis underlies the interfered cell cycle progression in Itpr2 ablated OPCs. Besides, blocking MAPK/ERK pathway significantly improves the delayed OPC differentiation and myelination in Itpr2 mutant. Notably, the resting [Ca2+ ]i is increased in Itpr2 ablated OPCs, with the elevation of several plasma calcium channels. Antagonists against these plasma calcium channels can normalize the resting [Ca2+ ]i level and enhance lineage progression in Itpr2-ablated OPCs. Together, the findings reveal novel insights for calcium homeostasis in manipulating developmental transition from OPCs to pre-OLs; additionally, the involvement of OLs-originated ITPR2 in depressive behaviors provides new therapeutic strategies to alleviate myelin-associated psychiatric disorders.

3.
J Exp Clin Cancer Res ; 43(1): 2, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38163881

RESUMO

BACKGROUND: Cisplatin (CDDP)-based chemotherapy is a standard first-line treatment for metastatic bladder cancer (BCa) patients, and chemoresistance remains a major challenge in clinical practice. Circular RNAs (circRNAs) have emerged as essential regulators in carcinogenesis and cancer progression. However, the role of circRNAs in mediating CDDP chemosensitivity has yet to be well elucidated in BCa. METHODS: CircSTX6 (hsa_circ_0007905) was identified by mining the public circRNA datasets and verified by Sanger sequencing, agarose gel electrophoresis, RNase R treatment and qRT-PCR assays. Then, function experiments were performed to evaluate the effects of circSTX6 on BCa metastasis. Luciferase reporter assay, RNA pull-down, RNA immunoprecipitation (RIP), RNA stability assay, Fluorescence in situ hybridization (FISH) and Immunofluorescence (IF) were conducted to evaluate the interaction among circSTX6, miR-515-3p, PABPC1 and SUZ12. Animal experiments were performed to explore the function of circSTX6 in tumor metastasis and CDDP sensitivity. RESULTS: We identified that circSTX6 was significantly upregulated in clinical samples and cells of BCa. Functionally, circSTX6 promoted cell migration and invasion both in vitro and in vivo. Mechanistically, circSTX6 could act as a miR-515-3p sponge and abolish its effect on SUZ12. Moreover, circSTX6 was confirmed to increase the stability of SUZ12 mRNA by interacting with a mRNA stabilizer PABPC1 and subsequently promote the expression of SUZ12. Importantly, silencing of circSTX6 improved the chemosensitivity of CDDP-resistant bladder cancer cells to CDDP. Furthermore, in vivo analysis supported that knockdown of circSTX6 attenuated CDDP resistance in BCa tumors. CONCLUSION: These studies demonstrate that circSTX6 plays a pivotal role in BCa metastasis and chemoresistance, and has potential to serve as a therapeutic target for treatment of BCa.


Assuntos
MicroRNAs , Neoplasias da Bexiga Urinária , Animais , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , MicroRNAs/genética , RNA Circular/genética , Hibridização in Situ Fluorescente , Regulação Neoplásica da Expressão Gênica , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Proteínas de Ligação a RNA/genética , RNA Mensageiro , Proliferação de Células , Linhagem Celular Tumoral , Fator de Iniciação 4A em Eucariotos/genética , RNA Helicases DEAD-box/genética
4.
Int J Biol Macromol ; 253(Pt 6): 127267, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37820903

RESUMO

Diabetes mellitus (DM) as one chronic metabolic disease was greatly increased over recent decades. The major agents treating diabetes have noticeable side effects as well as the tolerability problems. The bioactive dietary polysaccharides from abundant natural resources exhibit good hypoglycemic effect with rare adverse effects, which might serve as a candidate to prevent and treat diabetes. However, the correlations between the hypoglycemic mechanism of polysaccharides and their structure were not mentioned in several studies, what's more, most of the current hypoglycemic studies on polysaccharides were based on in vitro and in vivo experiments, and there was a lack of knowledge about the effects in human clinical trials. The aim of this review is to discuss recent literature about the variety of dietary polysaccharides with hypoglycemic activity, as well the mechanism of action and the structure-function relationship are highlighted. Meanwhile, the application of dietary polysaccharides in functional foods and clinical medicine are realized with an in-depth understanding. So as to promote the exploration of dietary polysaccharides in low glycemic healthy foods or clinical medicine to prevent and treat diabetes.


Assuntos
Diabetes Mellitus , Hipoglicemiantes , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/química , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Polissacarídeos/química , Diabetes Mellitus/tratamento farmacológico , Carboidratos da Dieta/uso terapêutico , Alimento Funcional
5.
Vet Res ; 54(1): 83, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37759250

RESUMO

The LuxS quorum sensing system is a widespread system employed by many bacteria for cell-to-cell communication. The luxS gene has been demonstrated to play a crucial role in intramacrophage survival of piscine Streptococcus agalactiae, but the underlying mechanism remains largely unknown. In this study, transcriptome analysis, followed by the luxS gene deletion and subsequent functional studies, confirmed that impaired bacterial survival inside macrophages due to the inactivation of luxS was associated with reduced transcription of the fruRKI operon, encoding the fructose-specific phosphotransferase system. Further, luxS was determined not to enhance the transcription of fruRKI operon by binding its promoter, but to upregulate the expression of this operon via affecting the binding ability of catabolite control protein A (CcpA) to the catabolite responsive element (cre) in the promoter of fruRKI. Collectively, our study identifies a novel and previously unappreciated role for luxS in bacterial intracellular survival, which may give a more thorough understanding of the immune evasion mechanism in S. agalactiae.


Assuntos
Regulação Bacteriana da Expressão Gênica , Streptococcus agalactiae , Animais , Streptococcus agalactiae/genética , Regiões Promotoras Genéticas , Percepção de Quorum , Óperon , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
6.
Nat Commun ; 14(1): 5935, 2023 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-37741817

RESUMO

Single-molecule Real-time Isoform Sequencing (Iso-seq) of transcriptomes by PacBio can generate very long and accurate reads, thus providing an ideal platform for full-length transcriptome analysis. We present an integrated computational toolkit named TAGET for Iso-seq full-length transcript data analyses, including transcript alignment, annotation, gene fusion detection, and quantification analyses such as differential expression gene analysis and differential isoform usage analysis. We evaluate the performance of TAGET using a public Iso-seq dataset and newly sequenced Iso-seq datasets from tumor patients. TAGET gives significantly more precise novel splice site prediction and enables more accurate novel isoform and gene fusion discoveries, as validated by experimental validations and comparisons with RNA-seq data. We identify and experimentally validate a differential isoform usage gene ECM1, and further show that its isoform ECM1b may be a tumor-suppressor in laryngocarcinoma. Our results demonstrate that TAGET provides a valuable computational toolkit and can be applied to many full-length transcriptome studies.


Assuntos
Análise de Dados , Perfilação da Expressão Gênica , Humanos , Fusão Gênica , RNA-Seq , Transcriptoma/genética , Proteínas da Matriz Extracelular
7.
Med Image Anal ; 90: 102953, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37734140

RESUMO

Congenital heart disease (CHD) is the most common type of birth defect. Without timely detection and treatment, approximately one-third of children with CHD would die in the infant period. However, due to the complicated heart structures, early diagnosis of CHD and its types is quite challenging, even for experienced radiologists. Here, we present an artificial intelligence (AI) system that achieves a comparable performance of human experts in the critical task of classifying 17 categories of CHD types. We collected the first-large CT dataset from three different CT machines, including more than 3750 CHD patients over 14 years. Experimental results demonstrate that it can achieve diagnosis accuracy (86.03%) comparable with junior cardiovascular radiologists (86.27%) in a World Health Organization appointed research and cooperation center in China on most types of CHD, and obtains a higher sensitivity (82.91%) than junior cardiovascular radiologists (76.18%). The accuracy of the combination of our AI system (97.20%) and senior radiologists achieves comparable results to that of junior radiologists and senior radiologists (97.16%) which is the current clinical routine. Our AI system can further provide 3D visualization of hearts to senior radiologists for interpretation and flexible review, surgeons for precise intuition of heart structures, and clinicians for more precise outcome prediction. We demonstrate the potential of our model to be integrated into current clinic practice to improve the diagnosis of CHD globally, especially in regions where experienced radiologists can be scarce.

8.
Molecules ; 28(9)2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37175285

RESUMO

A novel precolumn derivatization-GC-MS/MS method was developed for the determination of decoquinate residues in chicken tissues (muscle, liver, and kidney). The samples were extracted and purified by liquid-liquid extraction combined with solid-phase extraction and derivatized with acetic anhydride and pyridine. The recovery rates for decoquinate were 77.38~89.65%, and the intra-day and inter-day RSDs were 1.63~5.74% and 2.27~8.06%, respectively. The technique parameters meet the necessities for veterinary drug residue detection in China, the US, and the EU. Finally, the method was applied to analyze tissues of 60 chickens bought from a neighborhood supermarket, and solely one sample of chicken muscle contained 15.6 µg/kg decoquinate residue.


Assuntos
Decoquinato , Espectrometria de Massas em Tandem , Animais , Espectrometria de Massas em Tandem/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Galinhas , Músculos , Cromatografia Líquida de Alta Pressão/métodos , Extração em Fase Sólida
9.
BMC Genomics ; 24(1): 86, 2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36829105

RESUMO

BACKGROUND: Prenatal stress (PS) is considered as a risk factor for many mental disorders. PS-induced transcriptomic alterations may contribute to the functional dysregulation during brain development. Here, we used RNA-seq to explore changes of gene expression in the mouse fetal brain after prenatal exposure to chronic unpredictable mild stress (CUMS). RESULTS: We compared the stressed brains to the controls and identified groups of significantly differentially expressed genes (DEGs). GO analysis on up-regulated DEGs revealed enrichment for the cell cycle pathways, while down-regulated DEGs were mostly enriched in the neuronal pathways related to synaptic transmission. We further performed cell-type enrichment analysis using published scRNA-seq data from the fetal mouse brain and revealed cell-type-specificity for up- and down-regulated DEGs, respectively. The up-regulated DEGs were highly enriched in the radial glia, while down-regulated DEGs were enriched in different types of neurons. Cell deconvolution analysis further showed altered cell fractions in the stressed brain, indicating accumulation of neuroblast and impaired neurogenesis. Moreover, we also observed distinct brain-region expression pattern when mapping DEGs onto the developing Allen brain atlas. The up-regulated DEGs were primarily enriched in the dorsal forebrain regions including the cortical plate and hippocampal formation. Surprisingly, down-regulated DEGs were found excluded from the cortical region, but highly expressed on various regions in the ventral forebrain, midbrain and hindbrain. CONCLUSION: Taken together, we provided an unbiased data source for transcriptomic alterations of the whole fetal brain after chronic PS, and reported differential cell-type and brain-region vulnerability of the developing brain in response to environmental insults during the pregnancy.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Animais , Camundongos , Ciclo Celular , RNA-Seq , Encéfalo
10.
Eur Radiol ; 33(5): 3041-3051, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36571603

RESUMO

OBJECTIVES: This study aimed to investigate the association between the perivascular fat attenuation index (FAI) and the success of the antegrade percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). METHODS: This study evaluated patients with only one CTO lesion observed on conventional coronary angiography (CAG) who underwent coronary computed tomography angiography (CCTA) < 1 month before CAG, from 2018 to 2019. The clinical data, CCTA-based CTO lesion morphologic characteristics, and perivascular FAI of CTO lesions were recorded and analysed. RESULTS: In total, 156 patients with CTOs were enrolled in this study. Successful antegrade PCI (A-PCI) was achieved in 105 CTO lesions (67.3%). The perivascular FAI of the failed A-PCI group was significantly lower than the successful A-PCI group (-84.76 ± 10.44 Hounsfield unit (HU) vs. -67.54 ± 9.94 HU; p < 0.001), and the cut-off value determined by the receiver operating characteristic (ROC) curve was -77.50 HU. Multivariable analysis revealed no statistical significance in the clinical data, FAI ≤ -77.50 HU (odds ratio (OR): 33.96), negative remodeling (OR: 4.36), severe calcification degree (OR: 4.43) and occlusion length ≥ 20.25 mm (OR: 3.89) were independent predictors of A-PCI failure. The prediction performance of combining the three morphologic characteristics (severe calcification, occlusion length ≥ 20.25 mm, and negative remodeling) with FAI ≤ -77.50 HU was better than that of the three morphologic characteristics alone (0.93 versus 0.77, p < 0.001). CONCLUSIONS: As a non-invasive index for detecting coronary inflammation, FAI complements indicators based on coronary CTA well and may be helpful for choosing appropriate interventional strategies. KEY POINTS: • Perivascular FAI of CTO was significantly higher in the failed A-PCI group. • The combination of FAI with other morphological predictors showed higher predictive performance of failed A-PCI for CTOs. • FAI is a good complement to indicators based on coronary CTA.


Assuntos
Oclusão Coronária , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/métodos , Resultado do Tratamento , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/cirurgia , Angiografia Coronária/métodos , Tecido Adiposo/diagnóstico por imagem , Doença Crônica , Fatores de Risco
11.
Biol Psychiatry ; 93(3): 279-290, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36335068

RESUMO

BACKGROUND: GABAergic (gamma-aminobutyric acidergic) interneurons (INs) are highly heterogeneous, and Htr3a labels a subpopulation of cortical INs originating from the embryonic caudal ganglionic eminence. SETDB1 is one of the histone H3K9 methyltransferases and plays an essential role in the excitatory neurons, but its role in regulating cortical inhibitory INs remains largely unknown. METHODS: In this study, we generated transgenic mice with conditional knockout of Setdb1 in neural progenitor cells (Setdb1-NS-cKO) and GABAergic neurons (Setdb1-Gad2-cKO). In addition, we performed RNA sequencing, ATAC-seq (assay for transposase-accessible chromatin with sequencing), chromatin immunoprecipitation sequencing, luciferase assay, chromatin conformation capture, and CRISPR (clustered regularly interspaced short palindromic repeats)/dCas9 to study the epigenetic mechanism underlying SETDB1-mediated transcriptional regulation of Htr3a. We also performed in situ hybridization and whole-cell recording to evaluate the functional properties of cortical Htr3a+ INs and behavioral tests for mood. RESULTS: We detected significant upregulation of Htr3a expression in the embryonic ganglionic eminence of Setdb1-NS-cKO and identified the endogenous retroviral sequence RMER21B as a new target of SETDB1. RMER21B showed enhancer activity and formed distal chromatin interaction with the promoter of Htr3a. In addition, we observed an increased number and enhanced excitability of Htr3a+ INs in the knockout cortex. Moreover, Setdb1-Gad2-cKO mice exhibited anxiety- and depressive-like behaviors, which were partially reversed by a 5-HT3 receptor antagonist. CONCLUSIONS: These findings suggest that SETDB1 represses Htr3a transcription via RMER21B-mediated distal chromatin interaction in the embryonic ganglionic eminence and regulates the development of cortical Htr3a+ INs and mood behaviors.


Assuntos
Cromatina , Interneurônios , Camundongos , Animais , Histona Metiltransferases , Camundongos Transgênicos , Neurônios GABAérgicos , Receptores 5-HT3 de Serotonina , Histona-Lisina N-Metiltransferase/genética
12.
Microbes Infect ; 25(1-2): 105038, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35963567

RESUMO

The TonB system is required for the active transport of iron compounds across the outer membrane in Gram-negative bacteria. Our previous data indicated that three TonB systems act coordinately to contribute to the motility of Aeromonas hydrophila NJ-35. In this study, we found that flagellum biogenesis was defective in the ΔtonB123 mutant. Subcellular localization indicated that the flagellin subunits FlaA and FlaB were trapped in the cytoplasm of ΔtonB123 mutant with reduced molecular mass. Overexpression of FlaA or FlaB in the ΔtonB123 mutant was unable to restore the secretion of flagellin subunits. Further investigation demonstrated that flagellins in the ΔtonB123 mutant showed a weak affinity for the flagellin-specific chaperone FliS, which is necessary for the export of flagellins. Deglycosylation analysis indicated that flagellins in the cytoplasm of the ΔtonB123 mutant were almost nonglycosylated. Our data suggested that disruption of tonB123 impairs the formation of flagella by inhibiting flagellin glycosylation and decreasing the binding affinity of flagellin for the chaperone FliS. Taken together, our findings indicate a new role of the TonB system in flagellar biogenesis in A. hydrophila.


Assuntos
Aeromonas hydrophila , Flagelina , Flagelina/genética , Flagelina/metabolismo , Aeromonas hydrophila/genética , Aeromonas hydrophila/metabolismo , Flagelos/genética
13.
Foods ; 11(23)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36496702

RESUMO

An innovative and sensitive approach using high-performance liquid chromatography-photo diode array detection (HPLC-PDAD) was developed and optimized for the simultaneous determination of abamectin (ABM), ivermectin (IVM), albendazole (ABZ) and three metabolites in eggs. The samples were extracted with acetonitrile (MeCN)/water (90:10, v/v), and the extracts containing the targets were cleaned up and concentrated by a series of liquid-liquid extraction (LLE) steps. A reversed-phase C18 column and a mobile phase consisting of 0.1% trifluoroacetic acid (TFA) aqueous solution and methanol (MeOH) were utilized to perform optimal chromatographic separation. The developed method was validated on the basis of international guidelines. The limits of detection (LODs) and quantitation (LOQs) were 2.1-10.5 µg/kg and 7.8-28.4 µg/kg, respectively. Satisfactory linear relationships were observed for the targets in their corresponding concentration ranges. The mean recoveries ranged from 85.7% to 97.21% at 4 addition levels, with intraday and interday relative standard deviations (RSDs) in the ranges of 1.68-4.77% and 1.74-5.31%, respectively. The presented protocol was demonstrated to be applicable and reliable by being applied for the detection of target residues in locally sourced egg samples.

14.
Neurobiol Stress ; 21: 100495, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36532375

RESUMO

Stress-induced neuroinflammation is considered an important mechanism in the pathogenesis of depression. As immune effector cells in the brain, microglia play an essential role in neuroinflammation under stress, but the underlying mechanism remains controversial. Here, we performed RNA-seq and ATAC-seq to study microglia-specific epigenomic changes in mice after 12 weeks of exposure to mild stress. Our study revealed that chronic stress induced pronounced anxiety and depressive-like behavioral changes. However, microglia did not manifest a state of neuroinflammatory activation; instead, they displayed morphological changes characterized by hyper-ramification. Furthermore, we revealed large-scale transcriptional repression in microglia isolated from the stressed brain, including many interferon (IFN)-regulated genes (IRGs) and some encompassing DNA repeats. GSEA showed that the down-regulated genes were enriched in the IFN-mediated neuroimmune signaling pathways. In addition, integrative analysis with a published scRNA-seq dataset revealed that these down-regulated genes were enriched in a distinct subpopulation of "Interferon microglia". ATAC-seq analysis further showed that differential gene expression was positively correlated with the changes in chromatin accessibility, and the IFN-stimulated response element (ISRE) was enriched in the down-regulated ATAC-seq loci. Interestingly, this phenotype was not associated with the production of IFNs. Instead, the gene encoding Activating Transcription Factor 3 (ATF3) was significantly increased in the stressed microglia, which might contribute to the transcriptional repression of IRGs. Our study reported microglia-specific transcriptional repression of IRGs independent of the production of IFNs, providing some new insights into neuroimmune dysregulation under prolonged stress.

15.
Molecules ; 27(19)2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36234676

RESUMO

A quantitative and qualitative method using a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) detection approach was developed and validated for the analysis of tigecycline, four tetracyclines and their three 4-epimer derivatives in chicken muscle. Samples were extracted repeatedly with 0.1 mol/L Na2EDTA-McIlvaine buffer solution. After vortexing, centrifugation, solid-phase extraction, evaporation and reconstitution, the aliquots were separated using a C8 reversed-phase column (50 mm × 2.1 mm, 5 µm) with a binary solvent system consisting of methanol and 0.01 mol/L trichloroacetic acid aqueous solution. The typical validation parameters were evaluated in accordance with the acceptance criteria detailed in the guidelines of the EU Commission Decision 2002/657/EC and the U.S. Food and Drug Administration Bioanalytical Method Validation 05/24/18. The matrix-matched calibration curve was linear over the concentration range from the limit of quantitation (LOQ) to 400 µg/kg for doxycycline, and the calibration graphs for tetracycline, chlortetracycline, oxytetracycline, their 4-epimer derivatives and tigecycline showed a good linear relationship within the concentration range from the LOQ to 200 µg/kg. The limits of detection (LODs) for the eight targets were in the range of 0.06 to 0.09 µg/kg, and the recoveries from the fortified blank samples were in the range of 89% to 98%. The within-run precision and between-run precision, which were expressed as the relative standard deviations, were less than 5.0% and 6.9%, respectively. The applicability was successfully demonstrated through the determination of residues in 72 commercial chicken samples purchased from different sources. This approach provides a novel option for the detection of residues in animal-derived food safety monitoring.


Assuntos
Clortetraciclina , Oxitetraciclina , Animais , Antibacterianos/análise , Galinhas , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa , Doxiciclina , Ácido Edético , Metanol , Músculos/química , Oxitetraciclina/análise , Extração em Fase Sólida , Solventes , Espectrometria de Massas em Tandem/métodos , Tetraciclina , Tetraciclinas/análise , Tigeciclina , Ácido Tricloroacético
16.
Virulence ; 13(1): 1650-1665, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36152028

RESUMO

Protozoan predation has been demonstrated to be a strong driving force for bacterial defence strategies in the environment. Our previous study demonstrated that Aeromonas hydrophila NJ-35, which evolved small-colony variants (SCVs), displayed various adaptive traits in response to Tetrahymena thermophila predation, such as enhanced phage resistance. However, the evolutionary mechanisms are largely unknown. In this study, we performed a genome- and transcriptome-wide analysis of the SCV1, representing one strain of the SCVs, for identification of the genes of mutation and altered expression underlying this phage resistance phenotype. Our study demonstrated that phage resistance caused by T. thermophila predation was due to the downregulation of a flagellar biosynthesis regulator, flhF, in SCV1. Interestingly, we confirmed that phage resistance in SCV1 was not straightforwardly attributable to the absence of flagella but to FlhF-mediated secretion of extracellular protein that hinders phage adsorption. This finding improves our understanding of the mechanisms by which A. hydrophila lowers the susceptibility to phage infection under predation pressure, and highlights an important contribution of bacterium-protozoan interactions in driving the adaptive evolution of pathogens in complex environments.


Assuntos
Bacteriófagos , Tetrahymena thermophila , Aeromonas hydrophila/genética , Animais , Bacteriófagos/genética , Flagelos , Comportamento Predatório , Tetrahymena thermophila/genética , Transcriptoma
17.
Microbiol Spectr ; 10(4): e0211321, 2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-35861526

RESUMO

The clustered regularly interspaced palindromic repeat (CRISPR)-associated (Cas) system functions classically as a prokaryotic defense system against invading mobile genetic elements, such as phages, plasmids, and viruses. Our previous study revealed that CRISPR deletion caused increased transcription of capsular polysaccharide (CPS) synthesis-related genes and severely attenuated virulence in the hypervirulent piscine Streptococcus agalactiae strain GD201008-001. Here, we found that CRISPR deficiency resulted in reduced adhesion, invasion, and biofilm formation abilities in this strain by upregulating the production of CPS. However, enhanced CPS production was not responsible for the attenuated phenotype of the ΔCRISPR mutant. RNA degradation assays indicated that inhibited transcription of the cps operon by CRISPR RNA (crRNA) was not due to the base pairing of the crRNA with the cps mRNA but to the repression of the promoter activity of cpsA, which is a putative transcriptional regulator of the capsule locus. IMPORTANCE Beyond protection from invading nucleic acids, CRISPR-Cas systems have been shown to have an important role in regulating bacterial endogenous genes. In this study, we demonstrate that crRNA inhibits the transcription of the cps operon by repressing the activity of promoter PcpsA, leading to increases in the abilities of adhesion, invasion, and biofilm formation in S. agalactiae. This study highlights the regulatory role of crRNA in bacterial physiology and provides a new explanation for the mechanism of crRNA-mediated endogenous gene regulation in S. agalactiae.


Assuntos
Óperon , Streptococcus agalactiae , Biofilmes , Sistemas CRISPR-Cas , Polissacarídeos , Streptococcus agalactiae/genética , Virulência
18.
Exp Ther Med ; 24(1): 445, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35720624

RESUMO

[This corrects the article DOI: 10.3892/etm.2015.2220.].

19.
Front Cardiovasc Med ; 9: 804442, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35282363

RESUMO

Coronary artery disease (CAD) is the most common cause of death globally, and its diagnosis is usually based on manual myocardial (MYO) segmentation of MRI sequences. As manual segmentation is tedious, time-consuming, and with low replicability, automatic MYO segmentation using machine learning techniques has been widely explored recently. However, almost all the existing methods treat the input MRI sequences independently, which fails to capture the temporal information between sequences, e.g., the shape and location information of the myocardium in sequences along time. In this article, we propose a MYO segmentation framework for sequence of cardiac MRI (CMR) scanning images of the left ventricular (LV) cavity, right ventricular (RV) cavity, and myocardium. Specifically, we propose to combine conventional neural networks and recurrent neural networks to incorporate temporal information between sequences to ensure temporal consistency. We evaluated our framework on the automated cardiac diagnosis challenge (ACDC) dataset. The experiment results demonstrate that our framework can improve the segmentation accuracy by up to 2% in the Dice coefficient.

20.
Eur Radiol ; 32(1): 355-367, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34156553

RESUMO

OBJECTIVES: To construct models for predicting reintervention after thoracic endovascular aortic repair (TEVAR) of Stanford type B aortic dissection (TBAD). METHODS: A total of 192 TBAD patients who underwent TEVAR were included; 68 (35.4%) had indications for reintervention. Clinical characteristics, aorta characteristics on pre- and postoperative computed tomography angiography, and aorta characteristics on immediate postoperative aortic digital subtraction angiography were collected. The least absolute shrinkage and selection operator (LASSO) regression was applied to identify the risk factors for reintervention. Eight classifiers were used for modeling. The models were trained on 100 train-validation random splits with a ratio of 2:1. The performance was evaluated by the receiver operating characteristic curve. RESULTS: Seven predictors of reintervention were identified, including maximum false lumen diameter, aortic diameter measured at the level of approximately 15 mm distal to the left subclavian artery, aortic diameter measured at the level of the diaphragm, false lumen diameter measured at the level of the celiac artery, number of bare-metal and covered stents, number of bare-metal stents, and residual perfusion of the false lumen. Logistic regression (LR) yielded the highest performance, with an area under the curve of 0.802. A nomogram built for clinical use showed good calibration. The cutoff value for dividing patients into low- and high-risk subgroups was 0.413. Kaplan-Meier curves showed that the overall survival of high-risk patients was significantly shorter than that of low-risk patients (both p < 0.05). CONCLUSION: Our nomogram could predict the reintervention after TEVAR in patients with TBAD, which may facilitate patient selection and surveillance strategies. KEY POINTS: • Seven risk factors of reintervention after TEVAR of TBAD were identified for modeling. • Logistic regression performed best in predicting reintervention with an AUC of 0.802. • Patients with a high risk of reintervention had shorter OS than those with a low risk.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Humanos , Aprendizado de Máquina , Estudos Retrospectivos , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento
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