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1.
Medicine (Baltimore) ; 103(36): e39464, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39252309

RESUMEN

To more accurately diagnose and treat patients with different subtypes of thyroid cancer, we constructed a diagnostic model related to the iodine metabolism of THCA subtypes. THCA expression profiles, corresponding clinicopathological information, and single-cell RNA-seq were downloaded from TCGA and GEO databases. Genes related to thyroid differentiation score were obtained by GSVA. Through logistic analyses, the diagnostic model was finally constructed. DCA curve, ROC curve, machine learning, and K-M analysis were used to verify the accuracy of the model. qRT-PCR was used to verify the expression of hub genes in vitro. There were 104 crossover genes between different TDS and THCA subtypes. Finally, 5 genes (ABAT, CHEK1, GPX3, NME5, and PRKCQ) that could independently predict the TDS subpopulation were obtained, and a diagnostic model was constructed. ROC, DCA, and RCS curves exhibited that the model has accurate prediction ability. K-M and subgroup analysis results showed that low model scores were strongly associated with poor PFI in THCA patients. The model score was significantly negatively correlated with T cell follicular helper. In addition, the diagnostic model was significantly negatively correlated with immune scores. Finally, the results of qRT-PCR corresponded with bioinformatics results. This diagnostic model has good diagnostic and prognostic value for THCA patients, and can be used as an independent prognostic indicator for THCA patients.


Asunto(s)
Yodo , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Biología Computacional/métodos , Femenino , Masculino , Aprendizaje Automático , Persona de Mediana Edad , Glándula Tiroides/patología , Glándula Tiroides/metabolismo , Curva ROC , Diferenciación Celular , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo
2.
BMC Nurs ; 23(1): 617, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39227877

RESUMEN

BACKGROUND: "The hidden costs of informal caregiving" is an interdisciplinary concept. While caregivers make a significant contribution to the process of caregiving, they sacrifice their leisure time, and incur risks of dropping out of the job, impaired mental and physical health, and decreased well-being within the context of caregiving. Those invisible sacrifices are often overlooked and described as hidden costs of informal caregiving. However, the conceptualisation of hidden costs of informal caregiving has not yet been clarified and scientifically assessed. The research aimed to clarify the concept of hidden costs of informal caregiving and develop an operational definition. METHODS: Walker and Avant's concept analysis was conducted. Databases of CBM, CNKI, WanFang, VIP, PubMed, Embase, CINAHL, Web of Science, MEDLINE, Cochrane Library, Econlit, CINAHL and ProQuest were searched with the term "hidden costs of informal caregiving". Information about the uses of the concept, defining attributes, model cases, antecedents, consequences and empirical referents of hidden costs of informal caregiving was extracted and synthesized. RESULTS: A total of 25 articles were included. The six defining attributes of hidden costs of informal caregiving were identified as including "undertaken by informal caregivers", "the time costs of caregiving", "costs of career development" "physical well-being costs", "mental well-being costs" and "social relationship costs". Personal characteristics of the caregivers and care recipients, along with caregiving attributes, were among the antecedents. The consequences of hidden costs of informal caregiving resulted in negative influences which included poor quality of life, life-altering decisions, options for the type of care, some degree of economic hardship, decreased compliance with treatment plans and monetary value informal caregivers are willing to pay to be replaced. CONCLUSION: This concept analysis decisively illuminated the hitherto nebulous concept and expanded the contents of hidden costs of informal caregiving, which will foster a deeper appreciation of the invisible cost of caregivers. Moreover, it will provide a reference for the study of the hidden costs of informal caregiving in future, contribute to the development of assessment tools and theoretical models of hidden costs of informal caregiving, and create a basis for designing an evidence-based care program.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39271561

RESUMEN

Multidrug-resistant Escherichia coli (MDR-E. coli) is a global health concern. Lactic acid bacteria (LAB) are important probiotics that have beneficial effects on health, and in recent years, their influences in preventing foodborne pathogens-induced colitis have attracted much attention. Therefore, this study aimed to investigate the oral administration of Lactiplantibacillus plantarum NWAFU-BIO-BS29 as an emerging approach to alleviate MDR-E. coli-induced colitis in BALB/c mice model. To illustrate the mode of action of NWAFU-BIO-BS29 interventions with the gut microbiota and immune responses, the changes on the colonic mucosal barrier, regulatory of the gene expressions of inflammatory cytokines, re-modulating the intestinal microflora, and changes in physiological parameters were studied. The results indicated that daily supplementation of 200 µL fresh bacteria for 7 days had ameliorated the associated colitis and partially prevented the infection. The modes of action by ameliorating the inflammatory response, which destructed villous and then affected the intestinal barrier integrity, reducing the secretion of interleukins (6 and ß) and tumor necrosis factor (TNF-α) in serum by 87.88-89.93%, 30.73-35.98%, and 19.14-22.32%, respectively, enhancing the expressions of some epithelial integrity-related proteins in the mouse mucous layer of mucins 2 and 3, Claudin-1, and Occludin by 130.00-661.85%, 27.64-57.35%, 75.52-162.51%, and 139.36-177.73%, respectively, and 56.09-73.58% for toll-like receptor (TLR4) in colon tissues. Notably, the mouse gut microbiota analysis showed an increase in the relative abundance of beneficial bacteria, including Lactobacillus, Bacteriodales bacterium, Candidatus Saccharimonas, Enterorhabdus, and Bacilli. Furthermore, the probiotic promoted the proliferation of epithelia and goblet cells by increasing short-chain fatty acids (SCFAs) levels by 19.23-31.39%. In conclusion, L. plantarum NWAFU-BIO-BS29 has potential applications and can be considered a safe dietary supplement to ameliorate the colitis inflammation symptoms of MDR-E. coli infection.

4.
BMC Biol ; 22(1): 197, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39256779

RESUMEN

BACKGROUND: Cotton is an important economic crop and a host of Liriomyza sativae. Pectin methylesterase (PME)-mediated pectin metabolism plays an indispensable role in multiple biological processes in planta. However, the pleiotropic functions of PME often lead to unpredictable effects on crop resistance to pests. Additionally, whether and how PME affects susceptibility to Liriomyza sativae remain unclear. RESULTS: Here, we isolated GhPME36, which is located in the cell wall, from upland cotton (Gossypium hirsutum L.). Interestingly, the overexpression of GhPME36 in cotton caused severe susceptibility to Liriomyza sativae but increased leaf biomass in Arabidopsis. Cytological observations revealed that the cell wall was thinner with more demethylesterified pectins in GhPME36-OE cotton leaves than in WT leaves, whereas the soluble sugar content of GhPME36-OE cotton leaf cell walls was accordingly higher; both factors attracted Liriomyza sativae to feed on GhPME36-OE cotton leaves. Metabolomic analysis demonstrated that glucose was significantly differentially accumulated. Transcriptomic analysis further revealed DEGs enriched in glucose metabolic pathways when GhPME36 was overexpressed, suggesting that GhPME36 aggravates susceptibility to Liriomyza sativae by affecting both the structure and components of cell wall biosynthesis. Moreover, GhPME36 interacts with another pectin-modifying enzyme, GhC/VIF1, to maintain the dynamic stability of pectin methyl esterification. CONCLUSIONS: Taken together, our results reveal the cytological and molecular mechanisms by which GhPME36 aggravates susceptibility to Liriomyza sativae. This study broadens the knowledge of PME function and provides new insights into plant resistance to pests and the safety of genetically modified plants.


Asunto(s)
Pared Celular , Gossypium , Hojas de la Planta , Proteínas de Plantas , Gossypium/genética , Pared Celular/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Animales , Ascomicetos/fisiología , Hidrolasas de Éster Carboxílico/metabolismo , Hidrolasas de Éster Carboxílico/genética , Enfermedades de las Plantas/parasitología , Regulación de la Expresión Génica de las Plantas , Arabidopsis/genética , Plantas Modificadas Genéticamente/genética
5.
Environ Sci Technol ; 58(36): 16204-16214, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39190017

RESUMEN

Although hydrophilic modification of the membrane surface is widely adopted, polymeric membranes still suffer from irreversible fouling caused by hydrophilic components in surface water. Here, an ultrathin hydrogel layer (40 nm) with hydrophilic-hydrophobic textures was in situ grown onto the polysulfone ultrafiltration membrane surface using an organic-radical-initiated interfacial polymerization technique. The interfacial polymerization of hydrophilic and hydrophobic monomers ensured the molecular-scale distribution of hydrophilic and hydrophobic nanodomains on the membrane surface. These nanodomains, with their molecular lengths, facilitated dynamic repulsion interactions between the uniformly textured surface and foulant components with different degrees of hydrophilicity. Chemical force characterization confirmed that the adhesion force between the hydrophilic-hydrophobic textured membrane surface and foulants (dodecane, bovine serum albumin, and humic acid) was greatly reduced. Dynamic filtration experiments showed that a hydrophilic-hydrophobic textured membrane always possessed the largest water flux and the best antifouling performance. Furthermore, the foulant coverage ratio on the membrane surface was first evaluated by measuring changes in surface streaming potentials, which demonstrated a 69% reduction in the amount of foulant adhering to the hydrophilic-hydrophobic textured membrane surface. Therefore, the construction of hydrophilic-hydrophobic nanodomains on the membrane surface provides a promising strategy for alleviating membrane fouling caused by both hydrophobic and hydrophilic components during ultralow pressurized ultrafiltration processes.


Asunto(s)
Interacciones Hidrofóbicas e Hidrofílicas , Membranas Artificiales , Ultrafiltración , Incrustaciones Biológicas , Polímeros/química , Albúmina Sérica Bovina/química
6.
Front Chem ; 12: 1449536, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39206439

RESUMEN

Objective: The aim of the present study was to carry out a systematic research on bitterness quantification to provide a reference for scholars and pharmaceutical developers to carry out drug taste masking research. Significance: The bitterness of medications poses a significant concern for clinicians and patients. Scientifically measuring the intensity of drug bitterness is pivotal for enhancing drug palatability and broadening their clinical utility. Methods: The current study was carried out by conducting a systematic literature review that identified relevant papers from indexed databases. Numerous studies and research are cited and quoted in this article to summarize the features, strengths, and applicability of quantitative bitterness assessment methods. Results: In our research, we systematically outlined the classification and key advancements in quantitative research methods for assessing drug bitterness, including in vivo quantification techniques such as traditional human taste panel methods, as well as in vitro quantification methods such as electronic tongue analysis. It focused on the quantitative methods and difficulties of bitterness of natural drugs with complex system characteristics and their difficulties in quantification, and proposes possible future research directions. Conclusion: The quantitative methods of bitterness were summarized, which laid an important foundation for the construction of a comprehensive bitterness quantification standard system and the formulation of accurate, efficient and rich taste masking strategies.

7.
Mol Neurodegener ; 19(1): 62, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39183331

RESUMEN

BACKGROUND: Although WD repeat domain 45 (WDR45) mutations have been linked to ß -propeller protein-associated neurodegeneration (BPAN), the precise molecular and cellular mechanisms behind this disease remain elusive. This study aims to shed light on the impacts of WDR45-deficiency on neurodegeneration, specifically axonal degeneration, within the midbrain dopaminergic (DAergic) system. We hope to better understand the disease process by examining pathological and molecular alterations, especially within the DAergic system. METHODS: To investigate the impacts of WDR45 dysfunction on mouse behaviors and DAergic neurons, we developed a mouse model in which WDR45 was conditionally knocked out in the midbrain DAergic neurons (WDR45cKO). Through a longitudinal study, we assessed alterations in the mouse behaviors using open field, rotarod, Y-maze, and 3-chamber social approach tests. We utilized a combination of immunofluorescence staining and transmission electron microscopy to examine the pathological changes in DAergic neuron soma and axons. Additionally, we performed proteomic and lipidomic analyses of the striatum from young and aged mice to identify the molecules and processes potentially involved in the striatal pathology during aging. Further more, primary midbrain neuronal culture was employed to explore the molecular mechanisms leading to axonal degeneration. RESULTS: Our study of WDR45cKO mice revealed a range of deficits, including impaired motor function, emotional instability, and memory loss, coinciding with the profound reduction of midbrain DAergic neurons. The neuronal loss, we observed massive axonal enlargements in the dorsal and ventral striatum. These enlargements were characterized by the accumulation of extensively fragmented tubular endoplasmic reticulum (ER), a hallmark of axonal degeneration. Proteomic analysis of the striatum showed that the differentially expressed proteins were enriched in metabolic processes. The carbohydrate metabolic and protein catabolic processes appeared earlier, and amino acid, lipid, and tricarboxylic acid metabolisms were increased during aging. Of note, we observed a tremendous increase in the expression of lysophosphatidylcholine acyltransferase 1 (Lpcat1) that regulates phospholipid metabolism, specifically in the conversion of lysophosphatidylcholine (LPC) to phosphatidylcholine (PC) in the presence of acyl-CoA. The lipidomic results consistently suggested that differential lipids were concentrated on PC and LPC. Axonal degeneration was effectively ameliorated by interfering Lpcat1 expression in primary cultured WDR45-deficient DAergic neurons, proving that Lpcat1 and its regulated lipid metabolism, especially PC and LPC metabolism, participate in controlling the axonal degeneration induced by WDR45 deficits. CONCLUSIONS: In this study, we uncovered the molecular mechanisms underlying the contribution of WDR45 deficiency to axonal degeneration, which involves complex relationships between phospholipid metabolism, autophagy, and tubular ER. These findings greatly advance our understanding of the fundamental molecular mechanisms driving axonal degeneration and may provide a foundation for developing novel mechanistically based therapeutic interventions for BPAN and other neurodegenerative diseases.


Asunto(s)
Axones , Neuronas Dopaminérgicas , Lipidómica , Mesencéfalo , Ratones Noqueados , Proteómica , Animales , Ratones , Axones/metabolismo , Axones/patología , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/patología , Mesencéfalo/metabolismo , Mesencéfalo/patología , Degeneración Nerviosa/patología , Degeneración Nerviosa/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patología
8.
Methods Mol Biol ; 2841: 165-170, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39115775

RESUMEN

Vesicle trafficking is an essential cellular process conserved in eukaryotes to precisely transport proteins to their destinations. The plant endomembrane system plays a pivotal role in orchestrating this vesicle-mediated protein transport process, making its study essential for a comprehensive understanding of plant growth and development. Pharmaceutical analysis proves highly useful in investigating the plant endomembrane system. To facilitate further studies in this area, we present a summary of several commonly used chemical inhibitors in this chapter, providing a practical resource for researchers interested in the plant endomembrane system.


Asunto(s)
Transporte de Proteínas , Plantas/metabolismo , Membranas Intracelulares/metabolismo , Membranas Intracelulares/efectos de los fármacos , Proteínas de Plantas/metabolismo , Membrana Celular/metabolismo
9.
Int J Biol Macromol ; 279(Pt 2): 135154, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39214212

RESUMEN

Silver nanoparticles (AgNPs) have drawn a lot of attention from a variety of fields, particularly the biological and biomedical sciences. As a result, it is acknowledged that AgNPs' direct interactions with macromolecules such as DNA, proteins, and enzymes are essential for both therapeutic and nanotoxicological applications. Enzymes as important catalysts may interact with AgNP surfaces in a variety of ways. Therefore, mechanistic investigation into the molecular effects of AgNPs on enzyme conformation and function is necessary for a comprehensive assessment of their interactions. In this overview, we aimed to overview the various strategies for producing AgNPs. We then discussed the enzyme activity inhibition (EAI) mechanism by nanostructured particles, followed by an in-depth survey of the interaction of AgNPs with different enzymes. Furthermore, various parameters influencing the interaction of NPs and enzymes, as well as the antibacterial and anticancer effects of AgNPs in the context of the enzyme inhibitors, were discussed. In summary, useful information regarding the biological safety and possible therapeutic applications of AgNPs-enzyme conjugates may be obtained from this review.

10.
Sci Rep ; 14(1): 19142, 2024 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-39160211

RESUMEN

Cancer is one of the most concerning public health issues and breast cancer is one of the most common cancers in the world. The immune cells within the tumor microenvironment regulate cancer development. In this study, single immune cell data sets were used to identify marker gene sets for exhausted CD8 + T cells (CD8Tex) in breast cancer. Machine learning methods were used to cluster subtypes and establish the prognostic models with breast cancer bulk data using the gene sets to evaluate the impacts of CD8Tex. We analyzed breast cancer overexpressing and survival-associated marker genes and identified CD8Tex hub genes in the protein-protein-interaction network. The relevance of the hub genes for CD8 + T-cells in breast cancer was evaluated. The clinical associations of the hub genes were analyzed using bulk sequencing data and spatial sequencing data. The pan-cancer expression, survival, and immune association of the hub genes were analyzed. We identified biomarker gene sets for CD8Tex in breast cancer. CD8Tex-based subtyping systems and prognostic models performed well in the separation of patients with different immune relevance and survival. CRTAM, CLEC2D, and KLRB1 were identified as CD8Tex hub genes and were demonstrated to have potential clinical relevance and immune therapy impact. This study provides a unique view of the critical CD8Tex hub genes for cancer immune therapy.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , Linfocitos T CD8-positivos , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Femenino , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Biomarcadores de Tumor/genética , Pronóstico , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Regulación Neoplásica de la Expresión Génica , Mapas de Interacción de Proteínas/genética , Aprendizaje Automático
11.
CNS Neurosci Ther ; 30(8): e70003, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39161161

RESUMEN

AIMS: We evaluated the potential of Parkinson's disease (PD) fecal microbiota transplantation to initiate or exacerbate PD pathologies and investigated the underlying mechanisms. METHODS: We transplanted the fecal microbiota from PD patients into mice by oral gavage and assessed the motor and intestinal functions, as well as the inflammatory and pathological changes in the colon and brain. Furthermore, 16S rRNA gene sequencing combined with metabolomics analysis was conducted to assess the impacts of fecal delivery on the fecal microbiota and metabolism in recipient mice. RESULTS: The fecal microbiota from PD patients increased intestinal inflammation, deteriorated intestinal barrier function, intensified microglia and astrocyte activation, abnormal deposition of α-Synuclein, and dopaminergic neuronal loss in the brains of A53T mice. A mechanistic study revealed that the fecal microbiota of PD patients stimulated the TLR4/NF-κB/NLRP3 pathway in both the brain and colon. Additionally, multiomics analysis found that transplantation of fecal microbiota from PD patients not only altered the composition of the gut microbiota but also influenced the fecal metabolic profile of the recipient mice. CONCLUSION: The fecal microbiota from PD patients intensifies inflammation and neurodegeneration in A53T mice. Our findings demonstrate that imbalance and dysfunction in the gut microbiome play significant roles in the development and advancement of PD.


Asunto(s)
Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Enfermedad de Parkinson , Animales , Ratones , Enfermedad de Parkinson/microbiología , Enfermedad de Parkinson/metabolismo , Humanos , Microbioma Gastrointestinal/fisiología , Masculino , Inflamación/metabolismo , Inflamación/microbiología , Heces/microbiología , Ratones Transgénicos , Ratones Endogámicos C57BL , Femenino , alfa-Sinucleína/metabolismo , Encéfalo/metabolismo , Encéfalo/patología
12.
Int J Nanomedicine ; 19: 8437-8461, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39170101

RESUMEN

Data published in 2020 by the International Agency for Research on Cancer (IARC) of the World Health Organization show that breast cancer (BC) has become the most common cancer globally, affecting more than 2 million women each year. The complex tumor microenvironment, drug resistance, metastasis, and poor prognosis constitute the primary challenges in the current diagnosis and treatment of BC. Magnetic iron oxide nanoparticles (MIONPs) have emerged as a promising nanoplatform for diagnostic tumor imaging as well as therapeutic drug-targeted delivery due to their unique physicochemical properties. The extensive surface engineering has given rise to multifunctionalized MIONPs. In this review, the latest advancements in surface modification strategies of MIONPs over the past five years are summarized and categorized as constrast agents and drug delivery platforms. Additionally, the remaining challenges and future prospects of MIONPs-based targeted delivery are discussed.


Asunto(s)
Neoplasias de la Mama , Nanopartículas Magnéticas de Óxido de Hierro , Humanos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Nanopartículas Magnéticas de Óxido de Hierro/química , Sistemas de Liberación de Medicamentos/métodos , Propiedades de Superficie , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Animales , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapéutico , Microambiente Tumoral/efectos de los fármacos
13.
Sci Total Environ ; 949: 175215, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39098416

RESUMEN

Both soluble phosphorus (P) deficiency and petroleum hydrocarbon contamination represent challenges in soil environments. While phosphate-solubilizing bacteria and hydrocarbon-degrading bacteria have been identified and employed in environmental bioremediation, the bacteria co-adapted to soluble P deficiency and hydrocarbon contamination has rarely been reported. This study explored the ability of Acinetobacter oleivorans S4 (A. oleivorans S4) to solubilize phosphate using n-hexadecane (H), glucose (G), and a mixed carbon source (HG) in tricalcium phosphate (TCP) medium. A. oleivorans S4 exhibited robust growth in H-TCP, releasing 31 mg L-1 of soluble P. Conversely, A. oleivorans S4 barely grew in G-TCP, releasing 654 mg L-1 of soluble P. In HG-TCP, biomass surpassed that in H-TCP, with phosphate release comparable to that in G-TCP. HPLC analysis revealed a small amount of TCA cycle acids in H-TCP and a large amount of gluconate in G-TCP and HG-TCP. Transcriptomic analysis showed elevated expression of genes associated with alkane degradation, P starvation, N utilization, and trehalose synthesis in H-TCP, revealing the molecular co-adaptation mechanism of A. oleivorans S4. Furthermore, the addition of glucose enhanced alkane degradation, P and N utilization, and reduced trehalose synthesis. It indicated that incomplete glucose metabolism may provide energy for other reactions, and the increase in soluble P mediated by gluconate may alleviate oxidative stress. Overall, A. oleivorans S4 proves promising for remediating soluble P-deficient and hydrocarbon-contaminated environments, and glucose stimulates its transformation into a super phosphate-solubilizing bacterium.


Asunto(s)
Acinetobacter , Biodegradación Ambiental , Hidrocarburos , Fósforo , Fósforo/deficiencia , Fósforo/metabolismo , Acinetobacter/metabolismo , Hidrocarburos/metabolismo , Contaminantes del Suelo/metabolismo , Alcanos/metabolismo
14.
ISME J ; 18(1)2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-39073916

RESUMEN

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is associated with a loss or an imbalance of host-microorganism interactions. However, such interactions at protein levels remain largely unknown. Here, we applied a depletion-assisted metaproteomics approach to obtain in-depth host-microbiome association networks of IBD, where the core host proteins shifted from those maintaining mucosal homeostasis in controls to those involved in inflammation, proteolysis, and intestinal barrier in IBD. Microbial nodes such as short-chain fatty-acid producer-related host-microbial crosstalk were lost or suppressed by inflammatory proteins in IBD. Guided by protein-protein association networks, we employed proteomics and lipidomics to investigate the effects of UC-related core proteins S100A8, S100A9, and cytokines (IL-1ß, IL-6, and TNF-α) on gut bacteria. These proteins suppressed purine nucleotide biosynthesis in stool-derived in vitro communities, which was also reduced in IBD stool samples. Single species study revealed that S100A8, S100A9, and cytokines can synergistically or antagonistically alter gut bacteria intracellular and secreted proteome, with combined S100A8 and S100A9 potently inhibiting beneficial Bifidobacterium adolescentis. Furthermore, these inflammatory proteins only altered the extracellular but not intracellular proteins of Ruminococcus gnavus. Generally, S100A8 induced more significant bacterial proteome changes than S100A9, IL-1ß, IL-6, and TNF-α but gut bacteria degrade significantly more S100A8 than S100A9 in the presence of both proteins. Among the investigated species, distinct lipid alterations were only observed in Bacteroides vulgatus treated with combined S100A8, S100A9, and cytokines. These results provided a valuable resource of inflammatory protein-centric host-microbial molecular interactions.


Asunto(s)
Colitis Ulcerosa , Citocinas , Microbioma Gastrointestinal , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/metabolismo , Humanos , Citocinas/metabolismo , Calgranulina B/metabolismo , Calgranulina A/metabolismo , Proteómica , Heces/microbiología , Ruminococcus/metabolismo , Interacciones Microbiota-Huesped , Clostridiales
15.
Biomed Chromatogr ; 38(9): e5951, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38956830

RESUMEN

Loganic acid is an iridoid compound extracted from Gentianaceae plant Gentiana macrophylla Pall. It can effectively inhibit inflammation and tumor migration and has antioxidant activity. In this paper, we establish a simple, fast, sensitive and validated LC-MS method with the purpose of quantification of loganic acid in rat plasma with gliclazide as an internal standard (IS). Methanol was used to precipitate the protein in the plasma sample, and a C18 column (2.1 × 50 mm, 1.7 µm) was used for the separation of the target compound. Meanwhile, 0.1% formic acid water-methanol was employed as the mobile phase. Multiple reaction monitoring detection mode was adopted in detection with m/z 375.1 > 213.2 for loganic acid and m/z 322.1 > 169.9 for the IS, respectively, in negative ion scan mode. The linear range of calibration curve was 5.77-11,540.00 ng/ml, and the lower limit of detedtion was 2.89 ng/ml. The inter-day and intra-day precision and accuracy were <15% for lower limit of quantitation, low, middle and high quality control samples. This method was successfully used for the pharmacokinetic study of loganic acid in rat plasma at a dose range of 50-150 mg/kg for oral administration and 2 mg/kg for intravenous administration. The pharmacokinetic results showed that the oral bioavailability of loganic acid was low (2.71-5.58%).


Asunto(s)
Iridoides , Cromatografía Líquida con Espectrometría de Masas , Espectrometría de Masas en Tándem , Animales , Ratas , Iridoides/farmacocinética , Iridoides/sangre , Iridoides/química , Límite de Detección , Modelos Lineales , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de Masas en Tándem/métodos
16.
Front Pharmacol ; 15: 1417655, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39055491

RESUMEN

Silybum marianum (L.) Gaertn, a herbaceous plant with a long history in traditional medicine for the treatment of hepatobiliary diseases, particularly in Europe, which has attracted attention for its remarkable therapeutic effect. This review systematically summarizes the research progress in the botany, phytochemistry, pharmacology, comprehensive utilization and synthetic biology of S. marianum. Up to now, more than 20 types of flavonolignan components have been isolated from S. marianum. In addition, the rearch on fatty acids and triterpenoids is also constantly improving. Among them, silybin is the most active compound in flavonolignans components. Its pharmacological effects in vivo and in vitro include anti-inflammatory, antioxidant, anti-tumour, hypoglycaemic, neuroprotective and immunoregulatory properties. The use of coniferyl alcohol and taxifolin as substrates to produce silybin and isosilybin under the action of enzyme catalysis is the commonly used biosynthetic pathway of silymarin, which provides support for a comprehensive analysis of the synthetic pathway of silymarin. In addition to medicinal use, the extracts of plants also have broad application prospects in the production of food, healthcare products, cosmetics and other aspects. In addition, the chemical composition, pharmacological mechanism and synthetic biology of S. marianum need to be further studied, which is very important for its clinical efficacy and resource development.

17.
J Org Chem ; 89(15): 10678-10683, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39013075

RESUMEN

A radical cascade cyclization of 2-alkynylaniline derivatives with sulfonyl chlorides was developed to construct C3-sulfone methylene-substituted indolines in yields of 21 to 85% with a broad substrate scope under metal- and base-free conditions. This protocol could simultaneously build three new chemical bonds and employ a solvent-radical relay strategy, providing a rapid and concise approach toward an indoline framework. Scale-up reactions of this method and further transformations to afford useful indolines were also demonstrated.

18.
Traffic ; 25(7): e12952, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39073202

RESUMEN

SNX32 is a member of the evolutionarily conserved Phox (PX) homology domain- and Bin/Amphiphysin/Rvs (BAR) domain- containing sorting nexin (SNX-BAR) family of proteins, which play important roles in sorting and membrane trafficking of endosomal cargoes. Although SNX32 shares the highest amino acid sequence homology with SNX6, and has been believed to function redundantly with SNX5 and SNX6 in retrieval of the cation-independent mannose-6-phosphate receptor (CI-MPR) from endosomes to the trans-Golgi network (TGN), its role(s) in intracellular protein trafficking remains largely unexplored. Here, we report that it functions in parallel with SNX1 in mediating epidermal growth factor (EGF)-stimulated postendocytic trafficking of the epidermal growth factor receptor (EGFR). Moreover, SNX32 interacts directly with EGFR, and recruits SNX5 to promote sorting of EGF-EGFR into multivesicular bodies (MVBs) for lysosomal degradation. Thus, SNX32 functions distinctively from other SNX-BAR proteins to mediate signaling-coupled endolysosomal trafficking of EGFR.


Asunto(s)
Factor de Crecimiento Epidérmico , Receptores ErbB , Lisosomas , Transporte de Proteínas , Nexinas de Clasificación , Nexinas de Clasificación/metabolismo , Nexinas de Clasificación/genética , Receptores ErbB/metabolismo , Lisosomas/metabolismo , Humanos , Transporte de Proteínas/fisiología , Factor de Crecimiento Epidérmico/metabolismo , Células HeLa , Endosomas/metabolismo , Red trans-Golgi/metabolismo , Cuerpos Multivesiculares/metabolismo
19.
Front Psychiatry ; 15: 1402680, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39077626

RESUMEN

Background: Anxiety, depression, and sleep problems are prevalent comorbid mental disorders among university students. The World Health Organization (WHO) emphasized a mental health promotion objective, recommending the consideration of protective health-promoting factors in strategies aimed at preventing mental disorders. Integrating theoretically significant constructs (such as protective factors) enhances our comprehension of the intricate mechanisms that underpin mental disorders. This study employed network analysis to first identify core and bridge symptoms within comorbid mental disorders and then explore how health-promoting lifestyles (HPLs) were associated with these disorders. The ultimate goal is to offer health promotion recommendations to enhance students' quality of life. Methods: A total of 3,896 qualified university students participated in this study. Anxiety, depression, sleep problems, and HPLs were assessed using the GAD-7, PHQ-9, PSQI, and HPLP-II scales. A Gaussian Graphical Model was used to construct the networks. The Network Comparison Test was applied to determine whether the associations between HPLs and comorbid symptoms vary by gender, educational level, family sibling, and mental health status. Results: Low energy (PHQ4) had the highest strength centrality, followed by Daytime dysfunction (PSQI7) and Trouble relaxing (GAD4). Five bridge symptoms were identified: Daytime dysfunction (PSQI7), Self-harm even suicide (PHQ9), Sad mood (PHQ2), Low energy (PHQ4), and Feeling afraid (GAD7). Regarding protective HPLs, Physical activity, Spiritual growth, and Stress management generally emerged as the top three central mental health-promoting behaviors. Conclusion: Targeting core and bridge symptoms with timely and appropriate interventions can alleviate anxiety, depression, and sleep problems in this population. Moreover, promoting physical activity, fostering spiritual growth, and managing stress are likely to significantly enhance the overall mental health of university students.

20.
Inorg Chem ; 63(29): 13707-13713, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-38973588

RESUMEN

Due to the unique geometric and electronic structures, supported metal clusters with sizes below 3 nm have appealed to great interest in heterogeneous catalysis. However, these supported ultrasmall metal clusters would endure severe particle coalescences under high reaction temperatures. Herein, based on the technology of ball-milling processing, we propose a solid-state "surface-anchoring" strategy to synthesize thermally stabilized Al2O3-supported Ni nanoclusters. Interestingly, when the theoretical Ni loading weight was 1 wt %, highly dispersed Ni species were found where no Ni nanoparticles would be seen after 500 °C calcination. Until the Ni loading weight increased to 5 wt % and the calcination temperature increased to 750 °C, the Ni nanoparticles became significant but still with a size of only about 6.8 nm. With the small Ni nanoparticles, the final 5-Ni-Al2O3-OAm-750 sample worked well as methane dry reforming catalysts with excellent anticoking performance during a 500 h stability test.

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