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1.
Food Chem ; 464(Pt 1): 141579, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39406141

RESUMEN

To achieve high throughput detection of clenbuterol while reducing matrix interference, we developed a simple and integrated nano-inspection platform. Herein, based on the simplicity and convenience of paper chip, a multi-layer paper chip-chemiluminescence (CL) sensor was designed in the form of "48-well plate" type. The all-in-one paper chip-CL sensor has integrated the covalent organic frameworks (COFs) layer for sample matrix purification, high affinity nanobody layer for specific capture of target, and CL rapid response layer for the final determination. The signal readout was realized by the inhibitory effect of clenbuterol on the K3[Fe(CN)6] CL system. Detection of clenbuterol in pork meat was verified by measuring the CL intensity and satisfactory recoveries (85.9 %-97.3 %) were achieved. 48 samples could be simultaneously detected on one-chip in one-test, favoring the high-throughput detection. Especially, the work explored a new pathway for design of portable analytical instruments to achieve immediate on-site detection of hazards.

2.
Adv Mater ; : e2408485, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39344562

RESUMEN

Screening probiotics with specific functions is essential for advancing probiotic research. Current screening methods primarily use animal studies or clinical trials, which are inefficient and costly in terms of time, money, and labor. An intelligent intestine-on-a-chip integrating machine learning (ML) is developed to screen relief-enteritis functional probiotics. A high-throughput microfluidic chip combined with environment control systems provides a standardized and scalable intestinal microenvironment for multiple probiotic cocultures. An unsupervised ML-based score analyzer is constructed to accurately, comprehensively, and efficiently evaluate interactions between 12 Bifidobacterium strains and host cells of the colitis model in the intestine-on-a-chips. The most effective contender, Bifidobacterium longum 3-14, is discovered to relieve intestinal inflammation and enhance epithelial barrier function in vitro and in vivo. A distinct advantage of this strategy is that it can intelligently differentiate small therapeutic variations in probiotic strains and prioritize their efficacies, allowing for economical, efficient, accurate functional probiotics screening.

3.
Aging Cell ; : e14343, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39301860

RESUMEN

Aging-related metabolic disorders seriously affect the lifespan of middle-aged and older people, potentially due to disruptions in the adaptive immune and gut microbial profiles. Dietary intervention offers a promising strategy for maintaining metabolic health. This study aimed to investigate the ameliorative effect of 2'-fucosyllactose (2'-FL) on aging-induced metabolic dysfunction and the underlying mechanisms. The results revealed that 2'-FL significantly relieved aging-related metabolic disorders, including weight gain, lipid deposition, dyslipidemia, glucose intolerance, systemic inflammation, and abnormal hepatic metabolism. Flow cytometry analysis revealed a significant reduction in T cytotoxic (Tc), T helper (Th), and regulatory T (Treg) cells and a significant increase in Th17 cells in aged mice, while 2'-FL relieved the aging-induced proportional changes in Th and Th17 subtypes. The aging intestinal microecology was characterized by higher Th17/Treg ratios, impaired gut barrier function, lower gut bacterial diversity, decreased abundance of beneficial genera including Ligilactobacillus, Colidextribacter, Mucispirillum, and Lachnoclostridium, and increased abundance of harmful bacteria including Turicibacter and Desulfovibrio, which was ameliorated by 2'-FL treatment. These findings highlight that 2'-FL is an ideal dietary prebiotic for improving aging-related metabolic disorders by modulating both the adaptive immune system and the gut microbial profile.

4.
Appl Environ Microbiol ; : e0156424, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39297664

RESUMEN

Cronobacter sakazakii poses a significant threat, particularly to neonates and infants. Despite its strong pathogenicity, understanding of C. sakazakii biofilms and their role in infections remains limited. This study investigates the roles of HmsP and c-di-GMP in biofilm formation and identifies key genetic and proteomic elements involved. Gene knockout experiments reveal that HmsP and c-di-GMP are linked to biofilm formation in C. sakazakii. Comparative proteomic profiling identifies the lysozyme inhibitor protein LprI, which is downregulated in hmsP knockouts and upregulated in c-di-GMP knockouts, as a potential biofilm formation factor. Further investigation of the lprI knockout strain shows significantly reduced biofilm formation and decreased virulence in a rat infection model. Additionally, LprI is demonstrated to bind extracellular DNA, suggesting a role in anchoring C. sakazakii within the biofilm matrix. These findings enhance our understanding of the molecular mechanisms underlying biofilm formation and virulence in C. sakazakii, offering potential targets for therapeutic intervention and food production settings.IMPORTANCECronobacter sakazakii is a bacterium that poses a severe threat to neonates and infants. This research elucidates the role of the lysozyme inhibitor LprI, modulated by HmsP and c-di-GMP, and uncovers a key factor in biofilm formation and virulence. The findings offer crucial insights into the molecular interactions that enable C. sakazakii to form resilient biofilms and persist in hostile environments, such as those found in food production facilities. These insights not only enhance our understanding of C. sakazakii pathogenesis but also identify potential targets for novel therapeutic interventions to prevent or mitigate infections. This work is particularly relevant to public health and the food industry, where controlling C. sakazakii contamination in powdered infant formula is vital for safeguarding vulnerable populations.

5.
Neural Regen Res ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39101651

RESUMEN

Our recent study demonstrated that knockout of microRNA-301a attenuates migration and phagocytosis in macrophages. Considering that macrophages and Schwann cells synergistically clear the debris of degraded axons and myelin during Wallerian degeneration, which is a prerequisite for nerve regeneration, we hypothesized that microRNA-301a regulates Wallerian degeneration and nerve regeneration via impacts on Schwann cell migration and phagocytosis. Herein, we found low expression of microRNA-301a in intact sciatic nerves, with no impact of the microRNA-301a knockout on nerve structure and function. By contrast, we found significant upregulation of microRNA- 301a in injured sciatic nerves. We established a sciatic nerve crush model in microRNA-301a knockout mice, which exhibited attenuated morphological and functional regeneration following sciatic nerve crush injury. The microRNA-301a knockout also led to significantly inhibited Wallerian degeneration in an in vivo sciatic nerve-transection model and in an in vitro nerve explant block model. Schwann cells with the microRNA-301a knockout showed inhibition of phagocytosis and migration, which was reversible under transfection with microRNA-301a mimics. Rescue experiments involving transfection of microRNA-301a-knockout Schwann cells with microRNA-301a mimics or treatment with the C-X-C motif receptor 4 inhibitor WZ811 indicated the mechanistic involvement of the Yin Yang 1/C-X-C motif receptor 4 pathway in the role of microRNA-301a. Combined with our previous findings in macrophages, we conclude that microRNA-301a plays a key role in peripheral nerve injury and repair by regulating the migratory and phagocytic capabilities of Schwann cells and macrophages via the Yin Yang 1/C-X-C motif receptor 4 pathway.

6.
J Agric Food Chem ; 72(33): 18697-18707, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39165163

RESUMEN

Cronobacter sakazakii is a notorious foodborne opportunistic pathogen, particularly affecting vulnerable populations such as premature infants, and poses significant public health challenges. This study aimed to elucidate the role of the envZ/ompR genes in environmental tolerance, pathogenicity, and protein regulation of C. sakazakii. An envZ/ompR knockout mutant was constructed and assessed for its impact on bacterial growth, virulence, environmental tolerance, and protein regulation. Results demonstrate that deletion of envZ/ompR genes leads to reduced growth rate and attenuated virulence in animal models. Additionally, the knockout strain exhibited compromised environmental tolerance, particularly in desiccation and oxidative stress conditions, along with impaired adhesion and invasion abilities in epithelial cells. Proteomic analysis revealed significant alterations in protein expression and phosphorylation patterns, highlighting potential compensatory mechanisms triggered by gene deletion. Furthermore, investigation into protein deamidation and glucose metabolism uncovered a link between envZ/ompR deletion and energy metabolism dysregulation. Interestingly, the downregulation of MalK and GrxC proteins was identified as contributing factors to altered desiccation tolerance and disrupted redox homeostasis, respectively, providing mechanistic insights into the phenotypic changes observed. Overall, this study enhances understanding of the multifaceted roles of envZ/ompR in C. sakazakii physiology and pathogenesis, shedding light on potential targets for therapeutic intervention and food safety strategies.


Asunto(s)
Proteínas Bacterianas , Cronobacter sakazakii , Regulación Bacteriana de la Expresión Génica , Cronobacter sakazakii/genética , Cronobacter sakazakii/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Virulencia , Humanos , Animales , Infecciones por Enterobacteriaceae/microbiología , Ratones , Estrés Oxidativo
7.
Front Hum Neurosci ; 18: 1406670, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39188405

RESUMEN

Major depressive disorder (MDD) is currently the most common psychiatric disorder in the world. It characterized by a high incidence of disease with the symptoms like depressed mood, slowed thinking, and reduced cognitive function. Without timely intervention, there is a 20-30% risk of conversion to treatment-resistant depression (TRD) and a high burden for the patient, family and society. Numerous studies have shown that physical activity (PA) is a non-pharmacological treatment that can significantly improve the mental status of patients with MDD and has positive effects on cognitive function, sleep status, and brain plasticity. However, the physiological and psychological effects of different types of PA on individuals vary, and the dosage profile of PA in improving symptoms in patients with MDD has not been elucidated. In most current studies of MDD, PA can be categorized as continuous endurance training (ECT), explosive interval training (EIT), resistance strength training (RST), and mind-body training (MBT), and the effects on patients' depressive symptoms, cognitive function, and sleep varied. Therefore, the present study was based on a narrative review and included a large number of existing studies to investigate the characteristics and differences in the effects of different PA interventions on MDD. The study also investigated the characteristics and differences of different PA interventions in MDD, and explained the neural mechanisms through the results of multimodal brain function monitoring, including the intracranial environment and brain structure. It aims to provide exercise prescription and theoretical reference for future research in neuroscience and clinical intervention in MDD.

8.
J Cell Mol Med ; 28(16): e70012, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39187917

RESUMEN

Neuritin, also known as candidate plasticity gene 15 (CPG15), was first identified as one of the activity-dependent gene products in the brain. Previous studies have been reported that Neuritin induces neuritogenesis, neurite arborization, neurite outgrowth and synapse formation, which are involved in the development and functions of the central nervous system. However, the role of Neuritin in peripheral nerve injury is still unknown. Given the importance and necessity of Schwann cell dedifferentiation response to peripheral nerve injury, we aim to investigate the molecular mechanism of Neuritin steering Schwann cell dedifferentiation during Wallerian degeneration (WD) in injured peripheral nerve. Herein, using the explants of sciatic nerve, an ex vivo model of nerve degeneration, we provided evidences indicating that Neuritin vividly accelerates Schwann cell dedifferentiation. Moreover, we found that Neuritin promotes Schwann cell demyelination as well as axonal degeneration, phagocytosis, secretion capacity. In summary, we first described Neuritin acts as a positive regulator for Schwann cell dedifferentiation and WD after peripheral nerve injury.


Asunto(s)
Desdiferenciación Celular , Neuropéptidos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Células de Schwann , Nervio Ciático , Transducción de Señal , Serina-Treonina Quinasas TOR , Degeneración Walleriana , Células de Schwann/metabolismo , Células de Schwann/patología , Degeneración Walleriana/metabolismo , Degeneración Walleriana/patología , Animales , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Neuropéptidos/metabolismo , Neuropéptidos/genética , Nervio Ciático/lesiones , Nervio Ciático/metabolismo , Nervio Ciático/patología , Proteínas Ligadas a GPI/metabolismo , Proteínas Ligadas a GPI/genética , Ratas , Traumatismos de los Nervios Periféricos/metabolismo , Traumatismos de los Nervios Periféricos/patología , Ratas Sprague-Dawley , Axones/metabolismo , Axones/patología , Masculino , Fagocitosis , Ratones
9.
J Agric Food Chem ; 72(34): 18794-18808, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39160142

RESUMEN

The big progress of materials science along with chemical engineering and biotechnology has significantly promoted interdisciplinary development, achieving advanced analytical methodologies, improved inspection performance, as well as promising regulation principles for food safety. The very recent progress on nano/microporous architectures for agri-food science, including new strategies for precise inspection and new principles for controllable regulation of food hazards, are summarized and discussed. Major attention is paid to the newly emerged porous architectures with their derivative nano/microstructures contributing to food safety through their instinctive advantages including special material surface, extraordinary porous structure, ease-of-modification, and excellent diversity and variability. This review clearly and logically displays the research road maps and development trends for current food safety issues and give suggestive directions for future outlook as well as the bottleneck problems to be solved, not only smart inspection and analysis but also elimination and control of ever-emerging food hazards.


Asunto(s)
Contaminación de Alimentos , Inocuidad de los Alimentos , Porosidad , Contaminación de Alimentos/análisis , Contaminación de Alimentos/prevención & control , Nanoestructuras/química
10.
Nutrients ; 16(13)2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38999886

RESUMEN

Alcoholic liver damage is caused by long-term or heavy drinking, and it may further progress into alcoholic liver diseases (ALD). Probiotic supplements have been suggested for the prevention or improvement of liver damage. This study was designed to consider the ameliorative effects of Lactobacillus rhamnosus NKU FL1-8 isolated from infant feces against alcoholic liver damage. The mice were gavaged with a 50% ethanol solution and treated with 109 CFU of L. rhamnosus NKU FL1-8 suspension. The factors for liver function, oxidative stress, inflammation, gut microbiota composition, and intestinal barrier integrity were measured. The results showed that L. rhamnosus NKU FL1-8 could decrease the levels of aspartate aminotransferase (AST) to 61% and alanine aminotransferase (ALT) to 50% compared with ethanol given by gavage. It could inhibit the expression level of malondialdehyde (MDA), increase superoxide dismutase (SOD), glutathione (GSH) to relieve oxidative stress, and down-regulate the cytokines to decrease hepatic inflammation. After treatment, the level of triglycerides was reduced, and the expression levels of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and the peroxisome proliferators-activated receptor-α (PPAR-α) pathway were up-regulated. Additionally, the 16S rRNA sequencing analysis showed that L. rhamnosus NKU FL1-8 increased the relative abundance of Lactobacillus, Ruminococcaceae, etc. At the same time, L. rhamnosus NKU FL1-8 could significantly reduce lipopolysaccharides (LPS) and enhance intestinal tight junction proteins. These results demonstrated that L. rhamnosus NKU FL1-8 could reduce the level of oxidative stress, fat accumulation, and liver inflammation caused by alcohol in the host. The underlying mechanism could be that L. rhamnosus NKU FL1-8 inhibits LPS by regulating the gut microbiota and repairing the intestinal barrier. Thereby, these findings support L. rhamnosus NKU FL1-8 as a potential functional food for the relief of ALD.


Asunto(s)
Heces , Microbioma Gastrointestinal , Lacticaseibacillus rhamnosus , Hepatopatías Alcohólicas , Ratones Endogámicos C57BL , Estrés Oxidativo , Probióticos , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Heces/microbiología , Estrés Oxidativo/efectos de los fármacos , Hepatopatías Alcohólicas/prevención & control , Probióticos/farmacología , Ratones , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Masculino , Hígado/efectos de los fármacos , Hígado/metabolismo , Lactante , Etanol , Modelos Animales de Enfermedad
11.
Microorganisms ; 12(6)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38930585

RESUMEN

The widespread dissemination of carbapenem-resistant Klebsiella pneumoniae (CRKP) and its drug resistance transfer poses a global public health threat. While previous studies outlined CRKP's drug resistance mechanism, there is limited research on strategies inhibiting CRKP drug resistance spread. This study investigates the potential of Bifidobacterium longum (B. longum) FB1-1, a probiotic, in curbing the spread of drug resistance among CRKP by evaluating its cell-free supernatant (CFS) for antibacterial activity. Evaluating the inhibitory effect of FB1-1 CFS on CRKP drug resistance spread involved analyzing its impact on drug resistance and virulence gene expression; drug resistance plasmid transfer FB1-1 CFS exhibited an MIC range of 125 µL/mL against CRKP. After eight hours of co-culture, CFS achieved a 96% and 100% sterilization rate at two and four times the MIC, respectively. At sub-inhibitory concentrations (1/2× MIC), FB1-1 CFS reduced the expression of the bla_KPC gene, which is pivotal for carbapenem resistance, by up to 62.13% across different CRKP strains. Additionally, it markedly suppressed the expression of the uge gene, a key virulence factor, by up to 91%, and the fim_H gene, essential for bacterial adhesion, by up to 53.4%. Our study primarily focuses on determining the inhibitory effect of FB1-1 CFS on CRKP strains harboring the bla_KPC gene, which is a critical resistance determinant in CRKP. Furthermore, FB1-1 CFS demonstrated the ability to inhibit the transfer of drug resistance plasmids among CRKP strains, thus limiting the horizontal spread of resistance genes. This study highlights FB1-1 CFS's inhibitory effect on CRKP drug resistance spread, particularly in strains carrying the bla_KPC gene, thus offering a novel idea and theoretical foundation for developing antibacterial drugs targeting CRKP resistance.

12.
Food Chem ; 454: 139754, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38805930

RESUMEN

The complicated food matrix seriously limits the one-time test for the potential food hazards in non-targeted analysis. Accordingly, developing advanced sample pretreatment strategy to reduce matrix effects is of great significance. Herein, newly-integrated hollow-structured covalent organic frameworks (HCOFs) with large internal adsorption capacity and target-matched pore size were synthesized via etching the core-shell structured COFs. The as-prepared HCOFs could be directly applied for matrix clean-up of vegetable samples, while further modification of polydopamine (PDA) network facilitated application for animal samples. Both HCOFs and HCOFs@PDA with the comparable sizes to the matrix interference gave excellent adsorption performance to targets, achieving satisfied recoveries (70%-120%) toward 90 pesticides and 44 veterinary drugs in one-test, respectively. This work showed the great potential of the facile-integrated HCOFs with high stability and customized size to remove interference matrix and offered a universal strategy to achieve simultaneous screening of hazards with considerable quantity in high-throughput non-targeted analysis.


Asunto(s)
Contaminación de Alimentos , Estructuras Metalorgánicas , Verduras , Estructuras Metalorgánicas/química , Contaminación de Alimentos/análisis , Adsorción , Animales , Verduras/química , Polímeros/química , Plaguicidas/química , Plaguicidas/análisis , Drogas Veterinarias/análisis , Drogas Veterinarias/química , Indoles/química
13.
Am J Pathol ; 194(6): 1078-1089, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38417697

RESUMEN

Ferroptosis is a new form of cell death characterized by iron-dependent lipid peroxidation. Whether ferroptosis is involved in retinal microvascular dysfunction under diabetic condition is not known. Herein, the expression of ferroptosis-related genes in patients with proliferative diabetic retinopathy and in diabetic mice was determined with quantitative RT-PCR. Reactive oxygen species, iron content, lipid peroxidation products, and ferroptosis-associated proteins in the cultured human retinal microvascular endothelial cells (HRMECs) and in the retina of diabetic mice were examined. The association of ferroptosis with the functions of endothelial cells in vitro was evaluated. After administration of ferroptosis-specific inhibitor, Fer-1, the retinal microvasculature in diabetic mice was assessed. Characteristic changes of ferroptosis-associated markers, including glutathione peroxidase 4, ferritin heavy chain 1, long-chain acyl-CoA synthetase 4, transferrin receptor protein 1, and cyclooxygenase-2, were detected in the retinal fibrovascular membrane of patients with proliferative diabetic retinopathy, cultured HRMECs, and the retina of diabetic mice. Elevated levels of reactive oxygen species, lipid peroxidation, and iron content were found in the retina of diabetic mice and in cultured HRMECs. Ferroptosis was found to be associated with HRMEC dysfunction under high-glucose condition. Inhibition of ferroptosis with specific inhibitor Fer-1 in diabetic mice significantly reduced the severity of retinal microvasculopathy. Ferroptosis contributes to microvascular dysfunction in diabetic retinopathy, and inhibition of ferroptosis might be a promising strategy for the therapy of early-stage diabetic retinopathy.


Asunto(s)
Retinopatía Diabética , Ferroptosis , Especies Reactivas de Oxígeno , Retinopatía Diabética/patología , Retinopatía Diabética/metabolismo , Animales , Humanos , Ratones , Masculino , Especies Reactivas de Oxígeno/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/patología , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Peroxidación de Lípido , Ratones Endogámicos C57BL , Microvasos/patología , Microvasos/metabolismo , Hierro/metabolismo , Vasos Retinianos/metabolismo , Vasos Retinianos/patología
14.
Health Promot Int ; 39(1)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38386900

RESUMEN

Health literacy is closely related to the incidence of major chronic diseases and its related behaviors such as cancer-related behaviors. This study explored how the cancer health literacy level affects cancer-related behaviors. About one to two villages from six cities of Shandong province were selected as sample areas. Professionals conducted face-to-face interviews with the participants. Finally, 1200 residents completed 1085 effective questionnaires. Data were analysed from a cross-sectional survey in 2019, which included 1085 residents in six cities/counties of Shandong province, China. The result showed that residents with high cancer health literacy were more likely to eat fruits and vegetables frequently, avoid eating moldy food and take exercise. Besides, they were more likely to engage in health education and have a higher willingness to pay for cancer screenings. Most residents in Shandong province have a basic level of cancer health literacy. Improving the cancer health literacy of the population can be an effective strategy to promote a healthier lifestyle, thereby reducing the incidence rates related to cancers.


Asunto(s)
Alfabetización en Salud , Neoplasias , Humanos , Estudios Transversales , China/epidemiología , Frutas , Neoplasias/epidemiología , Neoplasias/prevención & control
15.
Opt Lett ; 49(3): 622-625, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38300074

RESUMEN

Characterization of single-frequency lasers (SFLs) requires a precise measurement of their phase noise. However, there exists a contradiction between the frequency range and laser phase noise measurement sensitivity in the delay self-heterodyne method. Achieving a broadband and highly sensitive phase noise measurement often requires overlapping the results obtained from different delay lengths. In this study, we present a precisely designed short-fiber recirculating delayed self-heterodyne (SF-RDSH) method that enables the broadband and highly sensitive laser phase noise measurement in a compact setup. By designing the length of the delay fiber based on a theoretical model, the RDSH technique with a shortest delay length of 200 m enables a highly sensitive laser phase noise measurement from 1 Hz to 1 MHz for the first time, to our knowledge. In the experiment, we demonstrate the broadband phase noise measurement of an SFL by analyzing the 1st and 10th beat notes.

16.
Curr Eye Res ; 49(4): 368-379, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38164922

RESUMEN

PURPOSE: Circular RNAs (circRNAs) are products of alternative splicing with roles as competitive endogenous RNAs or microRNA sponges, regulating gene expression and biological processes. However, the involvement of circRNAs in herpes simplex keratitis remains largely unexplored. METHODS: This study examines circRNA and miRNA expression profiles in primary human corneal epithelial cells infected with HSV-1, compared to uninfected controls, using microarray analysis. Bioinformatic analysis predicted the potential function of the dysregulated circRNAs and microRNA response elements (MREs) in these circRNAs, forming an interaction network between dysregulated circRNAs and miRNAs. RESULTS: A total of 332 circRNAs and 16 miRNAs were upregulated, while 80 circRNAs and six miRNAs were downregulated (fold change ≥2.0 and p < 0.05). Gene ontology (GO) and KEGG pathway analyses were performed on parental genes of dysregulated circRNAs to uncover potential functions in HSV-1 infection. Notably, miR-181b-5p, miR-338-3p, miR-635, and miR-222-3p emerged as pivotal miRNAs interacting with multiple dysregulated circRNAs. CONCLUSIONS: This comprehensive study offers insights into differentially expressed circRNAs and miRNAs during HSV-1 infection in corneal epithelial cells, shedding light on circRNA-miRNA interactions' potential role in herpes simplex keratitis pathogenesis.


Asunto(s)
Herpes Simple , Herpesvirus Humano 1 , Queratitis Herpética , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , Herpesvirus Humano 1/genética , Células Epiteliales/metabolismo , Queratitis Herpética/genética
17.
Blood ; 143(9): 786-795, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-37946283

RESUMEN

ABSTRACT: Older patients with advanced-stage classical Hodgkin lymphoma (cHL) have inferior outcomes compared with younger patients, potentially due to comorbidities and frailty. This noncomparative phase 2 study enrolled patients aged ≥60 years with cHL unfit for conventional chemotherapy to receive frontline brentuximab vedotin (BV; 1.8 mg/kg) with dacarbazine (DTIC; 375 mg/m2) (part B) or nivolumab (part D; 3 mg/kg). In parts B and D, 50% and 38% of patients, respectively, had ≥3 general comorbidities or ≥1 significant comorbidity. Of the 22 patients treated with BV-DTIC, 95% achieved objective response, and 64% achieved complete response (CR). With a median follow-up of 63.6 months, median duration of response (mDOR) was 46.0 months. Median progression-free survival (mPFS) was 47.2 months; median overall survival (mOS) was not reached. Of 21 patients treated with BV-nivolumab, 86% achieved objective response, and 67% achieved CR. With 51.6 months of median follow-up, mDOR, mPFS, and mOS were not reached. Ten patients (45%) with BV-DTIC and 16 patients (76%) with BV-nivolumab experienced grade ≥3 treatment-emergent adverse events; sensory peripheral neuropathy (PN; 27%) and neutropenia (9%) were most common with BV-DTIC, and increased lipase (24%), motor PN (19%), and sensory PN (19%) were most common with BV-nivolumab. Despite high median age, inclusion of patients aged ≤88 years, and frailty, these results demonstrate safety and promising durable efficacy of BV-DTIC and BV-nivolumab combinations as frontline treatment, suggesting potential alternatives for older patients with cHL unfit for initial conventional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01716806.


Asunto(s)
Fragilidad , Enfermedad de Hodgkin , Inmunoconjugados , Anciano de 80 o más Años , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Brentuximab Vedotina , Dacarbazina , Enfermedad de Hodgkin/patología , Nivolumab/efectos adversos
18.
Food Funct ; 14(24): 10924-10940, 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38009336

RESUMEN

Food allergy (FA) has become a prominent problem in public health. 2'-Fucosyllactose (2'-FL) was reported to alleviate FA symptoms; however, the regulatory mechanism is still unclear. This study evaluated the 2'-FL antiallergic potential in an ovalbumin (OVA)-sensitized mouse model and explored the systemic effects of 2'-FL on gut microecology and the intestinal immune barrier. The results showed that 2'-FL alleviated allergy symptoms, decreased serum allergic indicator levels, enhanced the intestinal barrier, and attenuated low-grade inflammation. The up-regulation of G protein-coupled receptors (GPRs) was associated with higher levels of short-chain fatty acids (SCFAs) in 2'-FL intervention mice. 2'-FL also improved the intestinal microbiota diversity and increased the abundance of Akkermansia, Lachnospiraceae UCG-006, and Ruminococcaceae while suppressing Muribaculaceae, Desulfovibrionaceae, and Erysipelotrichaceae. Additionally, 2'-FL ameliorated the imbalance of Th2/Th1, mainly by decreasing Th2-type immune response and enhanced CD4 + Foxp3 + Treg immunoreaction. These results suggest that 2'-FL restores intestinal barrier defects, gut microbiota disorder, and immune impairment while alleviating ovalbumin-induced allergic symptoms in FA mice.


Asunto(s)
Hipersensibilidad a los Alimentos , Ratones , Animales , Ovalbúmina , Hipersensibilidad a los Alimentos/tratamiento farmacológico , Trisacáridos , Ratones Endogámicos BALB C , Modelos Animales de Enfermedad , Citocinas
19.
Nutrients ; 15(19)2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37836387

RESUMEN

Obesity has emerged as one of the most prevalent chronic diseases worldwide. Our study was conducted to investigate the anti-obese potential of novel probiotic Bifidobacterium longum subsp. infantis FB3-14 (FB3-14) and the underlying molecular mechanisms in high-fat diet (HFD)-fed mice. The results demonstrated that an 8-week FB3-14 intervention significantly suppressed the HFD-induced body and fat weight gain and abnormal alterations of the serum lipid parameter, restoring the levels of cholesterol (4.29 mmol/L) and low-density lipoprotein cholesterol (3.42 mmol/L). FB3-14 treatment also attenuated adipocyte expansion, hepatic injury, and low-grade systemic inflammation and restored the expressions of lipid-metabolism-related genes, including Hsl, Leptin, and Adiponectin. Furthermore, FB3-14 was observed to reduce the Firmicutes/Bacteroidetes ratio in obese mice; increase the abundance of Akkermansia muciniphila, unclassified_Muribaculaceae, Lachnospiraceae_NK4A136_group, and Bifidobacterim; and upregulate G protein-coupled receptor41 associated with higher levels of butyric acid. These results indicate the protective effectiveness of FB3-14 in HFD-driven obesity and gut microbiota disorders, highlighting the promising potential of FB3-14 as a functional nutrition supplement.


Asunto(s)
Microbioma Gastrointestinal , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Obesidad/metabolismo , Bifidobacterium longum subspecies infantis , Butiratos/farmacología , Colesterol/farmacología , Bacteroidetes , Ratones Endogámicos C57BL
20.
Front Bioeng Biotechnol ; 11: 1201421, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37545892

RESUMEN

Objective: To explore the characteristics of Non-Negative Matrix Factorization (NNMF) in analyzing the mechanical characteristics of foot functional units during walking and running. Methods: Eighteen subjects (9 males and 9 females) were recruited, and the ground reaction force curves of each foot region during walking and running were collected using a plantar pressure measurement system. NNMF was used to extract the mechanical features of different foot regions and to determine the number of foot functional units. The differences between the base matrices of walking and running were compared by traditional t-tests, and the differences in coefficient matrices were compared by one-dimensional statistical parameter mapping. Results: 1) When the number of foot functional units for walking and running were both 2, the Variability Accounted For (VAF) by the matrix exceeded 0.90 (VAF walk = 0.96 ± 0.02, VAF run = 0.95 ± 0.04); 2) In foot functional unit 1, both walking and running exhibited buffering function, with the heel region being the main force-bearing area and the forefoot also participating in partial buffering; 3) In foot functional unit 2, both walking and running exhibited push-off function, with the middle part of the forefoot having a higher contribution weight; 4) In foot functional unit 1, compared to walking, the overall force characteristics of the running foot were greater during the support phase of the 0%-20% stage, with the third and fourth metatarsal areas having higher contribution weights and the lateral heel area having lower weights; 5) In foot functional unit 2, compared to walking, the overall force was higher during the beginning and 11%-69% stages of running, and lower during the 4%-5% and 73%-92% stages. During running, the thumb area, the first metatarsal area and the midfoot area had higher contribution weights than during walking; in the third and fourth metatarsal areas, the contribution weights were lower during running than during walking. Conclusion: Based on the mechanical characteristics of the foot, walking and running can both be decomposed into two foot functional units: buffering and push-off. The forefoot occupies a certain weight in both buffering and push-off functions, indicating that there may be a complex foot function transformation mechanism in the transverse arch of foot. Compared to walking, running completes push-off earlier, and the force region is more inclined towards the inner side of the foot, with the hallux area having a greater weight during push-off. This study suggests that NNMF is feasible for analyzing foot mechanical characteristics.

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