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1.
Mar Drugs ; 22(6)2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38921577

RESUMO

Sortase A (SrtA) is a cysteine transpeptidase that binds to the periplasmic membrane and plays a crucial role in attaching surface proteins, including staphylococcal protein A (SpA), to the peptidoglycan cell wall. Six pentacyclic polyketides (1-6) were isolated from the marine sponge Xestospongia sp., and their structures were elucidated using spectroscopic techniques and by comparing them to previously reported data. Among them, halenaquinol (2) was found to be the most potent SrtA inhibitor, with an IC50 of 13.94 µM (4.66 µg/mL). Semi-quantitative reverse transcription PCR data suggest that halenaquinol does not inhibit the transcription of srtA and spA, while Western blot analysis and immunofluorescence microscopy images suggest that it blocks the cell wall surface anchoring of SpA by inhibiting the activity of SrtA. The onset and magnitude of the inhibition of SpA anchoring on the cell wall surface in S. aureus that has been treated with halenaquinol at a value 8× that of the IC50 of SrtA are comparable to those for an srtA-deletion mutant. These findings contribute to the understanding of the mechanism by which marine-derived pentacyclic polyketides inhibit SrtA, highlighting their potential as anti-infective agents targeting S. aureus virulence.


Assuntos
Aminoaciltransferases , Antibacterianos , Proteínas de Bactérias , Parede Celular , Cisteína Endopeptidases , Poríferos , Staphylococcus aureus , Aminoaciltransferases/antagonistas & inibidores , Aminoaciltransferases/metabolismo , Cisteína Endopeptidases/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/antagonistas & inibidores , Animais , Poríferos/microbiologia , Antibacterianos/farmacologia , Antibacterianos/química , Policetídeos/farmacologia , Policetídeos/química
2.
Exp Mol Med ; 56(5): 1043-1054, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38689090

RESUMO

Biomedical research on the brain has led to many discoveries and developments, such as understanding human consciousness and the mind and overcoming brain diseases. However, historical biomedical research on the brain has unique characteristics that differ from those of conventional biomedical research. For example, there are different scientific interpretations due to the high complexity of the brain and insufficient intercommunication between researchers of different disciplines owing to the limited conceptual and technical overlap of distinct backgrounds. Therefore, the development of biomedical research on the brain has been slower than that in other areas. Brain biomedical research has recently undergone a paradigm shift, and conducting patient-centered, large-scale brain biomedical research has become possible using emerging high-throughput analysis tools. Neuroimaging, multiomics, and artificial intelligence technology are the main drivers of this new approach, foreshadowing dramatic advances in translational research. In addition, emerging interdisciplinary cooperative studies provide insights into how unresolved questions in biomedicine can be addressed. This review presents the in-depth aspects of conventional biomedical research and discusses the future of biomedical research on the brain.


Assuntos
Encéfalo , Pesquisa Translacional Biomédica , Humanos , Encéfalo/fisiologia , Animais , Neuroimagem/métodos , Encefalopatias/patologia , Inteligência Artificial , Pesquisa Biomédica
3.
Sci Total Environ ; 927: 172199, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38580108

RESUMO

Effect-directed analysis (EDA) is a crucial tool in environmental toxicology, effectively integrating toxicity testing with chemical analysis. The conventional EDA approach, however, presents challenges such as significant solvent consumption, extended analysis time, labor intensity, and potential contamination risks. In response, we introduce an innovative alternative to the conventional EDA. This method utilizes the MTT bioassay and online two-dimensional liquid chromatography (2D LC) coupled with high-resolution mass spectrometry (HR-MS), significantly reducing the fractionation steps and leveraging the enhanced sensitivity of the bioassay and automated chemical analysis. In the chemical analysis phase, a switching valve interface is employed for comprehensive analysis. We tested the performance of both the conventional and our online 2D LC-based methods using a household product. Both methods identified the same number of toxicants in the sample. Our alternative EDA is 22.5 times faster than the conventional method, fully automated, and substantially reduces solvent consumption. This novel approach offers ease, cost-effectiveness, and represents a paradigm shift in EDA methodologies. By integrating a sensitive bioassay with online 2D LC, it not only enhances efficiency but also addresses the challenges associated with traditional methods, marking a significant advancement in environmental toxicology research.


Assuntos
Poluentes Ambientais , Cromatografia Líquida/métodos , Poluentes Ambientais/toxicidade , Poluentes Ambientais/análise , Testes de Toxicidade/métodos , Monitoramento Ambiental/métodos , Espectrometria de Massas/métodos , Bioensaio/métodos , Ecotoxicologia/métodos
4.
J Nat Prod ; 87(5): 1330-1337, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38687892

RESUMO

Serratiomycin (1) is an antibacterial cyclic depsipeptide, first discovered from a Eubacterium culture in 1998. This compound was initially reported to contain l-Leu, l-Ser, l-allo-Thr, d-Phe, d-Ile, and hydroxydecanoic acid. In the present study, 1 and three new derivatives, serratiomycin D1-D3 (2-4), were isolated from a Serratia sp. strain isolated from the exoskeleton of a long-horned beetle. The planar structures of 1-4 were elucidated by using mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Comparison of the NMR chemical shifts and the physicochemical data of 1 to those of previously reported serratiomycin indeed identified 1 as serratiomycin. The absolute configurations of the amino units in compounds 1-4 were determined by the advanced Marfey's method, 2,3,4,6-tetra-O-acetyl-ß-d-glucopyranosyl isothiocyanate derivatization, and liquid chromatography-mass spectrometric (LC-MS) analysis. Additionally, methanolysis and the modified Mosher's method were used to determine the absolute configuration of (3R)-hydroxydecanoic acid in 1. Consequently, the revised structure of 1 was found to possess d-Leu, l-Ser, l-Thr, d-Phe, l-allo-Ile, and d-hydroxydecanoic acid. In comparison with the previously published structure of serratiomycin, l-Leu, l-allo-Thr, and d-Ile in serratiomycin were revised to d-Leu, l-Thr, and l-allo-Ile. The new members of the serratiomycin family, compounds 2 and 3, showed considerably higher antibacterial activities against Staphylococcus aureus and Salmonella enterica than compound 1.


Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Serratia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Serratia/química , Estrutura Molecular , Animais , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Besouros , Depsipeptídeos/farmacologia , Depsipeptídeos/química , Depsipeptídeos/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos
5.
Sci Adv ; 10(13): eadj9600, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38536932

RESUMO

Recently identified human FOXP3lowCD45RA- inflammatory non-suppressive (INS) cells produce proinflammatory cytokines, exhibit reduced suppressiveness, and promote antitumor immunity unlike conventional regulatory T cells (Tregs). In spite of their implication in tumors, the mechanism for generation of FOXP3lowCD45RA- INS cells in vivo is unclear. We showed that the FOXP3lowCD45RA- cells in human tumors demonstrate attenuated expression of CRIF1, a vital mitochondrial regulator. Mice with CRIF1 deficiency in Tregs bore Foxp3lowINS-Tregs with mitochondrial dysfunction and metabolic reprograming. The enhanced glutaminolysis activated α-ketoglutarate-mTORC1 axis, which promoted proinflammatory cytokine expression by inducing EOMES and SATB1 expression. Moreover, chromatin openness of the regulatory regions of the Ifng and Il4 genes was increased, which facilitated EOMES/SATB1 binding. The increased α-ketoglutarate-derived 2-hydroxyglutarate down-regulated Foxp3 expression by methylating the Foxp3 gene regulatory regions. Furthermore, CRIF1 deficiency-induced Foxp3lowINS-Tregs suppressed tumor growth in an IFN-γ-dependent manner. Thus, CRIF1 deficiency-mediated mitochondrial dysfunction results in the induction of Foxp3lowINS-Tregs including FOXP3lowCD45RA- cells that promote antitumor immunity.


Assuntos
Proteínas de Ligação à Região de Interação com a Matriz , Doenças Mitocondriais , Neoplasias , Humanos , Camundongos , Animais , Linfócitos T Reguladores , Ácidos Cetoglutáricos/metabolismo , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Citocinas/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo
6.
J Holist Nurs ; 42(1): 49-63, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37475533

RESUMO

Purpose: This qualitative study aimed to explore the perspectives of adolescents and young adults (AYA) on a planned nurse-patient dyadic storytelling intervention. Background: Cancer is a highly distressful event for AYA. AYA with cancer experience multidimensional suffering while dealing with their developmental transition from adolescence to young adulthood. Their unique needs require appropriate, well-tailored psychosocial support. Nurses can provide such support through storytelling approaches. METHOD: AYA cancer survivors participated in cross-sectional qualitative interviews to provide feedback on the nurse-patient storytelling intervention model. ANALYSIS: Qualitative content analysis was used to interpret and categorize the data. FINDINGS: Barriers and facilitators of the intervention emerged. Themes related to barriers included (a) the disadvantages of an online program, (b) the limitations of the in-person program, (c) interacting with nurses, (d) sharing personal stories with others, and (e) the timing of the program. Themes regarding facilitators included (a) benefits to AYA with cancer, (b) benefits to nurses, (c) benefits of online/in-person programs, and (d) willingness to participate. Conclusions: AYA with cancer may benefit from the nurse-patient dyadic storytelling intervention. Developing innovative methods to optimize and customize interventions based on preferences is essential. Future research should involve nurse feedback and tailored approaches for AYA with cancer.


Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Adolescente , Adulto Jovem , Adulto , Sobreviventes de Câncer/psicologia , Estudos Transversais , Neoplasias/psicologia , Relações Enfermeiro-Paciente , Comunicação
7.
Artigo em Inglês | MEDLINE | ID: mdl-37998279

RESUMO

As digital technologies rapidly integrate into Health Professions Education (HPE), understanding cyberethics is increasingly crucial. This scoping review explores the pedagogy of cyberethics in HPE, highlighting a significant gap in explicit definitions and conceptualizations. Additionally, the absence of specific theoretical frameworks in most documents raises concerns about research progression. Only four articles introduce educational interventions in cyberethics, indicating a promising avenue for future research. While comprehensive search methods are employed, limitations, including language biases, exist. Future investigations should broaden the discourse to encompass ethical implications of emerging technologies within HPE. Cultivating comprehensive, culturally sensitive, and inclusive guidelines is vital for ethical digital practices in the health care community.


Assuntos
Atenção à Saúde , Ocupações em Saúde
8.
Cell Rep ; 42(10): 113183, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37777962

RESUMO

Recent developments in genome sequencing have expanded the knowledge of genetic factors associated with late-onset Alzheimer's disease (AD). Among them, genetic variant ε4 of the APOE gene (APOE4) confers the greatest disease risk. Dysregulated glucose metabolism is an early pathological feature of AD. Using isogenic ApoE3 and ApoE4 astrocytes derived from human induced pluripotent stem cells, we find that ApoE4 increases glycolytic activity but impairs mitochondrial respiration in astrocytes. Ultrastructural and autophagy flux analyses show that ApoE4-induced cholesterol accumulation impairs lysosome-dependent removal of damaged mitochondria. Acute treatment with cholesterol-depleting agents restores autophagic activity, mitochondrial dynamics, and associated proteomes, and extended treatment rescues mitochondrial respiration in ApoE4 astrocytes. Taken together, our study provides a direct link between ApoE4-induced lysosomal cholesterol accumulation and abnormal oxidative phosphorylation.


Assuntos
Doença de Alzheimer , Células-Tronco Pluripotentes Induzidas , Humanos , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo , Astrócitos/metabolismo , Fosforilação Oxidativa , Células Cultivadas , Células-Tronco Pluripotentes Induzidas/metabolismo , Apolipoproteína E3/metabolismo , Colesterol/metabolismo , Doença de Alzheimer/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo
9.
Environ Pollut ; 334: 122166, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37429491

RESUMO

Fenton sludge is a byproduct of the Fenton process that contains large amounts of Fe and Ca. Because of the secondary contamination generated during the disposal of this byproduct, ecofriendly treatment methods are needed. In this study, we used Fenton sludge to remove the Cd discharged from a zinc smelter factory, using thermal activation to enhance the Cd adsorption capacity. Among the various temperatures considered (300-900 °C), the Fenton sludge that was thermally activated at 900 °C (TA-FS-900) adsorbed the highest amount of Cd because of its high specific surface area and high Fe content. Cd was adsorbed onto TA-FS-900 via complexation with C-OH, C-COOH, FeO-, and FeOH and cation exchange with Ca2+. The maximum adsorption of TA-FS-900 was 260.2 mg/g, indicating that TA-FS-900 is an efficient adsorbent, comparable to those reported in the literature. The initial Cd concentration in the zinc smelter wastewater discharged was 105.7 mg/L, 98.4% of which was removed by applying TA-FS-900, suggesting the applicability of TA-FS-900 for real wastewater containing high concentrations of various cations and anions. The leaching of heavy metals from TA-FS-900 was within the EPA standard limits. We concluded that the environmental impact of Fenton sludge disposal can be reduced, and the use of Fenton sludge can add value to the treatment of industrial wastewater in terms of the circular economy and environment.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Esgotos , Zinco , Cádmio , Estudos de Viabilidade , Eliminação de Resíduos Líquidos/métodos , Adsorção
10.
Exp Mol Med ; 55(1): 108-119, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36599935

RESUMO

nArgBP2, a candidate gene for intellectual disability, is a postsynaptic protein critical for dendritic spine development and morphogenesis, and its knockdown (KD) in developing neurons severely impairs spine-bearing excitatory synapse formation. Surprisingly, nArgBP2 KD in mature neurons did not cause morphological defects in the existing spines at rest, raising questions of how it functions in mature neurons. We found that unlike its inaction at rest, nArgBP2 KD completely inhibited the enlargement of dendritic spines during chemically induced long-term potentiation (cLTP) in mature neurons. We further found that nArgBP2 forms condensates in dendritic spines and that these condensates are dispersed by cLTP, which spatiotemporally coincides with spine head enlargement. Condensates with CaMKII phosphorylation-deficient mutant or CaMKII inhibition are neither dispersed nor accompanied by spine enlargement during cLTP. We found that nArgBP2 condensates in spines exhibited liquid-like properties, and in heterologous and in vitro expression systems, nArgBP2 undergoes liquid-liquid phase separation via multivalent intermolecular interactions between SH3 domains and proline-rich domains. It also forms coacervates with CaMKIIα, which is rapidly dissembled by calcium/CaMKIIα-dependent phosphorylation. We further showed that the interaction between nArgBP2 and WAVE1 competes with nArgBP2 phase separation and that blocking the nArgBP2-WAVE1 interaction prevents spine enlargement during cLTP. Together, our results suggest that nArgBP2 at rest is confined to the condensates but is released by CaMKIIα-mediated phosphorylation during synaptic plasticity, which regulates its timely interaction with WAVE1 to induce spine head enlargement in mature neurons.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Espinhas Dendríticas , Espinhas Dendríticas/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Condensados Biomoleculares , Plasticidade Neuronal/fisiologia , Potenciação de Longa Duração/fisiologia , Sinapses/metabolismo , Hipocampo/metabolismo
11.
J Am Chem Soc ; 145(3): 1886-1896, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36634356

RESUMO

The logical and effective discovery of macrolactams, structurally unique natural molecules with diverse biological activities, has been limited by a lack of targeted search methods. Herein, a targeted discovery method for natural macrolactams was devised by coupling genomic signature-based PCR screening of a bacterial DNA library with spectroscopic signature-based early identification of macrolactams. DNA library screening facilitated the efficient selection of 43 potential macrolactam-producing strains (3.6% of 1,188 strains screened). The PCR amplicons of the amine-deprotecting enzyme-coding genes were analyzed to predict the macrolactam type (α-methyl, α-alkyl, or ß-methyl) produced by the hit strains. 1H-15N HSQC-TOCSY NMR analysis of 15N-labeled culture extracts enabled macrolactam detection and structural type assignment without any purification steps. This method identified a high-titer Micromonospora strain producing salinilactam (1), a previously reported α-methyl macrolactam, and two Streptomyces strains producing new α-alkyl and ß-methyl macrolactams. Subsequent purification and spectroscopic analysis led to the structural revision of 1 and the discovery of muanlactam (2), an α-alkyl macrolactam with diene amide and tetraene chromophores, and concolactam (3), a ß-methyl macrolactam with a [16,6,6]-tricyclic skeleton. Detailed genomic analysis of the strains producing 1-3 identified putative biosynthetic gene clusters and pathways. Compound 2 displayed significant cytotoxicity against various cancer cell lines (IC50 = 1.58 µM against HCT116), whereas 3 showed inhibitory activity against Staphylococcus aureus sortase A. This genomic and spectroscopic signature-based method provides an efficient search strategy for new natural macrolactams and will be generally applicable for the discovery of nitrogen-bearing natural products.


Assuntos
Streptomyces , Estrutura Molecular , Lactamas Macrocíclicas/farmacologia , Lactamas Macrocíclicas/química , Streptomyces/metabolismo , Genômica , Reação em Cadeia da Polimerase , Família Multigênica
12.
IEEE Trans Vis Comput Graph ; 29(2): 1424-1437, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-34591770

RESUMO

Dendritic spines are dynamic, submicron-scale protrusions on neuronal dendrites that receive neuronal inputs. Morphological changes in the dendritic spine often reflect alterations in physiological conditions and are indicators of various neuropsychiatric conditions. However, owing to the highly dynamic and heterogeneous nature of spines, accurate measurement and objective analysis of spine morphology are major challenges in neuroscience research. Most conventional approaches for analyzing dendritic spines are based on two-dimensional (2D) images, which barely reflect the actual three-dimensional (3D) shapes. Although some recent studies have attempted to analyze spines with various 3D-based features, it is still difficult to objectively categorize and analyze spines based on 3D morphology. Here, we propose a unified visualization framework for an interactive 3D dendritic spine analysis system, DXplorer, that displays 3D rendering of spines and plots the high-dimensional features extracted from the 3D mesh of spines. With this system, users can perform the clustering of spines interactively and explore and analyze dendritic spines based on high-dimensional features. We propose a series of high-dimensional morphological features extracted from a 3D mesh of dendritic spines. In addition, an interactive machine learning classifier with visual exploration and user feedback using an interactive 3D mesh grid view ensures a more precise classification based on the spine phenotype. A user study and two case studies were conducted to quantitatively verify the performance and usability of the DXplorer. We demonstrate that the system performs the entire analytic process effectively and provides high-quality, accurate, and objective analysis.


Assuntos
Gráficos por Computador , Espinhas Dendríticas , Espinhas Dendríticas/fisiologia , Neurônios , Aprendizado de Máquina , Interpretação Estatística de Dados
13.
Am J Hosp Palliat Care ; 40(1): 34-42, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35535490

RESUMO

BACKGROUND: Recurrent or refractory cancer often results in substantial and extensive physical, emotional, psychosocial, and spiritual burdens for children and their families. However, the therapeutic benefits of legacy interventions in children with recurrent or refractory cancer have been examined only recently, with limited attention to specific effects on children's coping abilities. OBJECTIVE: The purpose of this study was to determine the effects of a digital storytelling-legacy intervention on the adaptive coping of children with recurrent or refractory cancer. METHODS: This study used a 2-arm randomized, waitlist-controlled trial design. A total of 150 children with recurrent or refractory cancer and their parents were recruited via Facebook advertisements. RESULTS: The analysis sample included 92 dyads (35-intervention group, 57-control group). The legacy intervention showed small and statistically nonsignificant effects on primary-control and disengagement coping strategies among children with recurrent or refractory cancer. CONCLUSIONS: Legacy interventions using readily accessible digital storytelling have the potential to enhance the adaptive coping skills among children with recurrent or refractory cancer. Further research should determine how to enhance interventions tailored to this population to optimize the benefits.


Assuntos
Adaptação Psicológica , Neoplasias , Criança , Humanos , Pais/psicologia , Neoplasias/terapia , Neoplasias/psicologia , Emoções , Internet
14.
Nurse Educ ; 48(3): E73-E78, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36450277

RESUMO

BACKGROUND: Given the wide range of metaverse technologies, there is a need to synthesize evidence of metaverse pedagogy used effectively for nursing education. PURPOSE: This umbrella review synthesized systematic reviews on the use of metaverse in nursing education. METHODS: A search was performed in MEDLINE, EMBASE, CINAHL, Web of Science, and Education Full Text. This umbrella review was conducted with reference to the Joanna Briggs Institute (JBI) Reviewer's Manual and reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The JBI Critical Appraisal Checklist for Systematic Review was used to assess the quality of studies. RESULTS: The final review comprised 15 articles published between 2013 and 2021, most of which indicate that metaverse interventions support increased knowledge, self-confidence, engagement, satisfaction, and performance in nursing students. Several articles in this review presented mixed findings related to certain learning outcomes. CONCLUSION: This umbrella review supports the viability and effectiveness of metaverse in nursing education.


Assuntos
Educação em Enfermagem , Estudantes de Enfermagem , Humanos , Pesquisa em Educação em Enfermagem , Aprendizagem , Escolaridade
15.
Mol Cell Proteomics ; 21(11): 100424, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36220603

RESUMO

Astrocytes are major supportive glia and immune modulators in the brain; they are highly secretory in nature and interact with other cell types via their secreted proteomes. To understand how astrocytes communicate during neuroinflammation, we profiled the secretome of human astrocytes following stimulation with proinflammatory factors. A total of 149 proteins were significantly upregulated in stimulated astrocytes, and a bioinformatics analysis of the astrocyte secretome revealed that the brain renin-angiotensin system (RAS) is an important mechanism of astrocyte communication. We observed that the levels of soluble form of aminopeptidase N (sANPEP), an RAS component that converts angiotensin (Ang) III to Ang IV in a neuroinflammatory milieu, significantly increased in the astrocyte secretome. To elucidate the role of sANPEP and Ang IV in neuroinflammation, we first evaluated the expression of Ang IV receptors in human glial cells because Ang IV mediates biological effects through its receptors. The expression of angiotensin type 1 receptor was considerably upregulated in activated human microglial cells but not in human astrocytes. Moreover, interleukin-1ß release from human microglial cells was synergistically increased by cotreatment with sANPEP and its substrate, Ang III, suggesting the proinflammatory action of Ang IV generated by sANPEP. In a mouse neuroinflammation model, brain microglial activation and proinflammatory cytokine expression levels were increased by intracerebroventricular injection of sANPEP and attenuated by an enzymatic inhibitor and neutralizing antibody against sANPEP. Collectively, our results indicate that astrocytic sANPEP-induced increase in Ang IV exacerbates neuroinflammation by interacting with microglial proinflammatory receptor angiotensin type 1 receptor, highlighting an important role of indirect crosstalk between astrocytes and microglia through the brain RAS in neuroinflammation.


Assuntos
Astrócitos , Microglia , Animais , Camundongos , Humanos , Microglia/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Sistema Renina-Angiotensina , Antígenos CD13/metabolismo , Doenças Neuroinflamatórias , Encéfalo/metabolismo , Modelos Animais de Doenças
16.
Sci Adv ; 8(37): eadc9317, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36112688

RESUMO

Lipids are crucial components of cellular function owing to their role in membrane formation, intercellular signaling, energy storage, and homeostasis maintenance. In the brain, lipid dysregulations have been associated with the etiology and progression of neurodegeneration and other neurological pathologies. Hence, brain lipids are emerging as important potential targets for the early diagnosis and prognosis of neurological diseases. This review aims to highlight the significance and usefulness of lipidomics in diagnosing and treating brain diseases. We explored lipid alterations associated with brain diseases, paying attention to organ-specific characteristics and the functions of brain lipids. As the recent advances in brain lipidomics would have been impossible without advances in analytical techniques, we provide up-to-date information on mass spectrometric approaches and integrative analysis with other omic approaches. Last, we present the potential applications of lipidomics combined with artificial intelligence techniques and interdisciplinary collaborative research for treating brain diseases with clinical heterogeneities.


Assuntos
Encefalopatias , Lipidômica , Inteligência Artificial , Encéfalo , Encefalopatias/diagnóstico , Encefalopatias/etiologia , Humanos , Metabolismo dos Lipídeos , Lipídeos/química
17.
Food Microbiol ; 107: 104094, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35953183

RESUMO

The closely related species, Lacticaseibacillus casei, L. paracasei, L. rhamnosus, L. chiayiensis, and L. zeae, are difficult to accurately discriminate by conventional identification methods. In this study, the bioTyper and in-house database of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was evaluated to discriminate five Lacticaseibacillus species. From the mass spectra of 130 isolates aligned with databases, 118 strains were correctly identified. On the other hand, databases could not accurately differentiate 12 isolates such as L. casei, L. rhamnosus and L. chiayiensis because the same colony was identified as two species with similar score. To overcome the database's limitations, the mass spectra were analyzed to discover species-specific protein peaks. The peaks at 6731 ± 1, 6849 ± 1, 7008 ± 1, 7376 ± 1, and 2593 ± 1 m/z were specifically found in the reference strains of L. casei, L. paracasei, L. rhamnosus, L. chiayiensis, and L. zeae, respectively. These peaks confirmed that the five peaks were consistently present in each species using 130 strains isolated from food samples. Our results demonstrate the high-resolution of MALDI-TOF MS technique for rapid and accurate classification of five species when used with databases coupled to specific peaks.


Assuntos
Lacticaseibacillus casei , Lasers , Especificidade da Espécie , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
18.
Sci Total Environ ; 847: 157482, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35901873

RESUMO

Catalytic oxidation is a feasible method for remediating volatile organic compounds (VOCs), due to its lower energy consumption and mineralization of VOCs into H2O and CO2. Noble metal-based catalysts are preferred for the catalytic oxidation of VOCs because of their superior activity, but they are usually deactivated by thermal aging which sinters the metal particles. Here, we report that Pt-Pd/Al2O3 thermally aged at 700-900 °C in air showed enhanced catalytic activity for toluene oxidation in humid conditions. There were electronic and structural changes in the thermally aged Pt-Pd/Al2O3, as confirmed by numerous analyses. Both Pt and Pd existed in a metallic rather than oxidized state without additional reduction steps. The noble metal particles were assembled to form Pt-Pd alloy, in the form of isolated Pd atoms surrounded by Pt atoms. This specific alloy structure was found to be crucial to the observed enhancement in catalytic toluene oxidation at low temperature.


Assuntos
Tolueno , Compostos Orgânicos Voláteis , Ligas/química , Dióxido de Carbono , Catálise , Eletrônica , Metais , Oxirredução , Compostos Orgânicos Voláteis/química
19.
J Oral Microbiol ; 14(1): 2088937, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35756538

RESUMO

Background: Streptococcus mutans, an important Gram-positive pathogen in dental caries, uses sortase A (SrtA) to anchor surface proteins to the bacterial cell wall, thereby promoting biofilm formation and attachment to the tooth surface. Design: Based on activity-guided separation, inhibitors of S. mutans SrtA were isolated from Juniperus chinensis and identified through combined spectroscopic analysis. Further effects of isolated SrtA inhibitor on S. mutans were evaluated on bacterial aggregation, adherence and biofilm formation. Results: Six compounds (1-6) were isolated from the dried heartwood of J. chinensis. A novel compound designated 3',3"-dihydroxy-(-)-matairesinol (1) was identified, which exhibited potent inhibitory activity toward S. mutans SrtA (IC50 = 16.1 µM) without affecting microbial viability (minimum inhibitory concentration > 300 µM). The results of subsequent bioassays using compound 1 indicated that this compound inhibits S. mutans aggregation, adhesion and biofilm formation on solid surfaces by inhibiting SrtA activity. The onset and magnitude of inhibition of adherence and biofilm formation in S. mutans treated with compound 1 at 4× the SrtA IC50 are comparable to the behaviors of the untreated srtA-deletion mutant. Conclusion: Our findings suggest that small-molecule inhibitors of S. mutans SrtA may be useful for the prevention of dental plaque and treatment of dental microbial diseases.

20.
Commun Biol ; 5(1): 431, 2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534680

RESUMO

Various optical clearing approaches have been introduced to meet the growing demand for 3D volume imaging of biological structures. Each has its own strengths but still suffers from low transparency, long incubation time, processing complexity, tissue deformation, or fluorescence quenching, and a single solution that best satisfies all aspects has yet been developed. Here, we develop OptiMuS, an optimized single-step solution that overcomes the shortcomings of the existing aqueous-based clearing methods and that provides the best performance in terms of transparency, clearing rate, and size retention. OptiMuS achieves rapid and high transparency of brain tissues and other intact organs while preserving the size and fluorescent signal of the tissues. Moreover, OptiMuS is compatible with the use of lipophilic dyes, revealing DiI-labeled vascular structures of the whole brain, kidney, spleen, and intestine, and is also applied to 3D quantitative and comparative analysis of DiI-labeled vascular structures of glomeruli turfs in normal and diseased kidneys. Together, OptiMuS provides a single-step solution for simple, fast, and versatile optical clearing method to obtain high tissue transparency with minimum structural changes and is widely applicable for 3D imaging of various whole biological structures.


Assuntos
Imageamento Tridimensional , Imagem Óptica , Encéfalo/diagnóstico por imagem , Corantes , Imageamento Tridimensional/métodos , Imagem Óptica/métodos
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