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1.
Food Chem ; 462: 140909, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39208727

RESUMEN

Probiotics serve a very important role in human health. However, probiotics have poor stability during processing, storage, and gastrointestinal digestion. The gellan gum (GG) is less susceptible to enzymatic degradation and resistant to thermal and acidic environments. This study investigated the effect of casein (CS)-GG emulsions to encapsulate Lactiplantibacillus plantarum CICC 6002 (L. plantarum CICC 6002) on its storage stability, thermal stability, and gastrointestinal digestion. L. plantarum CICC 6002 was suspended in palm oil and emulsions were prepared using CS or CS-GG complexes. We found the CS-GG emulsions improved the viability of L. plantarum CICC 6002 after storage, pasteurization, and digestion compared to the CS emulsions. In addition, we investigated the influence of the gellan gum concentration on emulsion stability, and the optimal stability was observed in the emulsion prepared by CS-0.8% GG complex. This study provided a new strategy for the protection of probiotics based on CS-GG delivery system.


Asunto(s)
Caseínas , Emulsiones , Lactobacillus plantarum , Polisacáridos Bacterianos , Probióticos , Emulsiones/química , Probióticos/química , Polisacáridos Bacterianos/química , Caseínas/química , Humanos , Lactobacillus plantarum/química , Lactobacillus plantarum/metabolismo , Pasteurización , Tracto Gastrointestinal/microbiología , Tracto Gastrointestinal/metabolismo , Viabilidad Microbiana/efectos de los fármacos , Composición de Medicamentos , Digestión , Almacenamiento de Alimentos
2.
Cell Biosci ; 14(1): 129, 2024 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-39420439

RESUMEN

BACKGROUND: Ferroptosis, a newly identified form of regulated cell death triggered by small molecules or specific conditions, plays a significant role in virus-associated carcinogenesis. However, whether tumours arising after high-risk HPV integration are associated with ferroptosis is unexplored and remains enigmatic. METHODS: High-risk HPV16 integration was analysed by high-throughput viral integration detection (HIVID). Ferroptosis was induced by erastin, and the levels of ferroptosis were assessed through the measurement of lipid-reactive oxygen species (ROS), malondialdehyde (MDA), intracellular Fe2+ level and transmission electron microscopy (TEM). Additionally, clinical cervical specimens and an in vivo xenograft model were utilized for the study. RESULTS: Expression of HPV16 integration hot spot c-Myc negatively correlates with ferroptosis during the progression of cervical squamous cell carcinoma (CSCC). Further investigation revealed that the upregulated oncogene miR-142-5p in HPV16-integrated CSCC cells served as a critical downstream effector of c-Myc in its target network. Inhibiting miR-142-5p significantly decreased the ferroptosis-suppressing effect mediated by c-Myc. Through a combination of computational and experimental approaches, HOXA5 was identified as a key downstream target gene of miR-142-5p. Overexpression of miR-142-5p suppressed HOXA5 expression, leading to decreased accumulation of intracellular Fe2+ and lipid peroxides (ROS and MDA). HOXA5 increased the sensitivity of CSCC cells to erastin-induced ferroptosis via transcriptional downregulation of SLC7A11, a negative regulator of ferroptosis. Importantly, c-Myc knockdown increased the anti-tumour activity of erastin by promoting ferroptosis both in vitro and in vivo. CONCLUSIONS: Collectively, these data indicate that HPV16 integration hot spot c-Myc plays a novel and indispensable role in ferroptosis resistance by regulating the miR-142-5p/HOXA5/SLC7A11 signalling axis and suggest a potential therapeutic approach for HPV16 integration-related CSCC.

3.
Neurobiol Dis ; 202: 106702, 2024 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-39406290

RESUMEN

Abnormal accumulation of insoluble α-synuclein (α-Syn) inclusions in neurons, neurites, and glial cells is the defining neuropathology of synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy. Accumulation of α-Syn inclusions in the amygdala has been well-documented in post-mortem studies of PD and DLB brains, as well as preclinical animal models of these conditions. Though α-Syn pathology is closely associated with neurodegeneration, there is a poor correlation between neuronal loss in the amygdala and the clinical features of PD and DLB. Moreover, functional interaction between the cerebral cortex and the amygdala is critical to regulating emotion, motivation, and social behaviors. The cortico-amygdala functional interaction is likely to be disrupted by the development of α-Syn pathology in the brain. Thus, we hypothesize that neuronal α-Syn inclusions disrupt cortical modulation of the amygdala circuits and are sufficient to drive social behavioral deficits. In the present work, we designed a series of longitudinal studies to rigorously measure the time courses of neurodegeneration, functional impairment of cortico-amygdala connectivity, and development of amygdala-dependent social behavioral deficits to test this hypothesis. We injected α-Syn preformed fibrils (PFFs) into the dorsal striatum to induce α-Syn aggregation in the amygdala and the medial prefrontal cortex (mPFC) of C57BL6 mice of both sexes, followed by a detailed analysis of temporal development of α-Syn pathology, synaptic deficits, and neuronal loss in the amygdala, as well as behavioral deficits at 3-12 months post injections. Development of α-Syn inclusions caused losses of cortical axon terminals and cell death in the basolateral amygdala (BLA) at 6- and 12-months post injections, respectively. At a relatively early stage of 3 months post injections, the connection strength of the mPFC-BLA synapse was decreased in PFFs-injection mice compared to controls. Meanwhile, the PFFs-injected mice showed impaired social interaction behavior, which was rescued by chemogenetic stimulation of mPFC-BLA connections. Altogether, we presented a series of evidence to delineate circuit events in the amygdala associated with the accumulation of α-Syn inclusions in the mouse brain, highlighting that functional impairment of the amygdala is sufficient to cause social behavior deficits. The present work further suggests that early circuit modulation could be an effective approach to alleviate symptoms associated with α-Syn pathology, necessitating studies of functional consequences of α-Syn aggregation.

4.
Environ Health (Wash) ; 2(10): 712-720, 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39474435

RESUMEN

In this study, we conducted exposure experiments on egg-laying hens to explore the toxicokinetics and maternal transfer characteristics of lipophilic and proteinophilic halogenated organic pollutants (HOPs). The lipophilic HOPs included polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and dechlorane plus (DPs), while the proteinophilic HOPs included perfluorocarboxylic acids (PFCAs). The results revealed that most of lipophilic HOPs exhibit lower depuration rate (k d) than PFCAs. The k d of lipophilic HOPs correlated with the octanol-water partition coefficient (log K OW) values in a V-shaped curve, whereas that of PFCAs correlated with the protein-water partition coefficient (log K PW) values in an inverted V-shaped curve. The depuration rate, rather than the uptake rate, was a leading factor in determining the bioaccumulation potential of HOPs in hens. Although the dominant factors determining the tissue distribution of the two types of compounds were explicit (fats vs phospholipids), chemical-specific tissue distribution was still observed. The egg-maternal concentration ratio was dependent on the exposure status, concentration, and maternal tissue choice. Using a single maternal tissue may not be an appropriate method for assessing chemical maternal transfer potential. PFCAs have a greater maternal transfer potential (>80% of the total body burden) than lipophilic HOPs (approximately 30% for BDE209 and DPs, and less than 10% for the others). Their lipophilic and partly proteinophilic nature makes the toxicokinetics and maternal transfer characteristics of BDE209 and DPs different from those of other lipophilic HOPs. These findings are crucial for enhancing our understanding of the behavior and fate of HOPs in egg-laying hens.

5.
Res Sq ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39281856

RESUMEN

Dysfunction of the cerebral cortex is thought to underlie motor and cognitive impairments in Parkinson disease (PD). While cortical function is known to be suppressed by abnormal basal ganglia output following dopaminergic degeneration, it remains to be determined how the deposition of Lewy pathology disrupts cortical circuit integrity and function. Moreover, it is also unknown whether cortical Lewy pathology and midbrain dopaminergic degeneration interact to disrupt cortical function in late-stage. To begin to address these questions, we injected α-synuclein (αSyn) preformed fibrils (PFFs) into the dorsolateral striatum of mice to seed αSyn pathology in the cortical cortex and induce degeneration of midbrain dopaminergic neurons. Using this model system, we reported that αSyn aggregates accumulate in the motor cortex in a layer- and cell-subtype-specific pattern. Particularly, intratelencephalic neurons (ITNs) showed earlier accumulation and greater extent of αSyn aggregates relative to corticospinal neurons (CSNs). Moreover, we demonstrated that the intrinsic excitability and inputs resistance of αSyn aggregates-bearing ITNs in the secondary motor cortex (M2) are increased, along with a noticeable shrinkage of cell bodies and loss of dendritic spines. Last, neither the intrinsic excitability of CSNs nor their thalamocortical input was altered by a partial striatal dopamine depletion associated with αSyn pathology. Our results documented motor cortical neuronal hyperexcitability associated with αSyn aggregation and provided a novel mechanistic understanding of cortical circuit dysfunction in PD.

6.
Viruses ; 16(9)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39339860

RESUMEN

Allergic asthma is characterized by increased type 2 inflammation, including eosinophils. Subjects with allergic asthma have recurrent symptoms due to their constant exposure to environmental allergens, such as house dust mite (HDM), which can be further exacerbated by respiratory infections like rhinovirus. The immunoproteasome (IP) is a proteolytic machinery that is induced by inflammatory mediators during virus infection, but the role of the IP in airway allergic inflammation during rhinovirus infection remains unknown. Wild-type (WT) and IP knockout (KO) mice were challenged with HDM. At 48 h after the last HDM challenge, mice were infected with rhinovirus 1B (RV-A1B) for 24 h. After HDM and RV-A1B treatment, IP KO (vs. WT) mice had significantly more lung eosinophils and neutrophils, as well as a significantly higher viral load, but less IFN-beta expression, compared to WT mice. A TLR3 agonist polyinosinic-polycytidylic acid (Poly I:C) treatment after RV-A1B infection in HDM-challenged IP KO mice significantly increased IFN-beta expression and reduced viral load, with a minimal effect on the number of inflammatory cells. Our data suggest that immunoproteasome is an important mechanism functioning to prevent excessive inflammation and viral infection in allergen-exposed mice, and that Poly I:C could be therapeutically effective in enhancing the antiviral response and lessening the viral burden in lungs with IP deficiency.


Asunto(s)
Ratones Noqueados , Poli I-C , Complejo de la Endopetidasa Proteasomal , Rhinovirus , Receptor Toll-Like 3 , Animales , Receptor Toll-Like 3/agonistas , Receptor Toll-Like 3/genética , Ratones , Complejo de la Endopetidasa Proteasomal/metabolismo , Poli I-C/farmacología , Infecciones por Picornaviridae/inmunología , Carga Viral , Pyroglyphidae/inmunología , Pulmón/patología , Pulmón/inmunología , Pulmón/virología , Asma/inmunología , Asma/tratamiento farmacológico , Eosinófilos/inmunología , Inflamación/inmunología , Hipersensibilidad/inmunología , Hipersensibilidad/tratamiento farmacológico , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Interferón beta/genética , Interferón beta/inmunología
7.
bioRxiv ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39091827

RESUMEN

Dysfunction of the cerebral cortex is thought to underlie motor and cognitive impairments in Parkinson disease (PD). While cortical function is known to be suppressed by abnormal basal ganglia output following dopaminergic degeneration, it remains to be determined how the deposition of Lewy pathology disrupts cortical circuit integrity and function. Moreover, it is also unknown whether cortical Lewy pathology and midbrain dopaminergic degeneration interact to disrupt cortical function in late-stage. To begin to address these questions, we injected α-synuclein (αSyn) preformed fibrils (PFFs) into the dorsolateral striatum of mice to seed αSyn pathology in the cortical cortex and induce degeneration of midbrain dopaminergic neurons. Using this model system, we reported that αSyn aggregates accumulate in the motor cortex in a layer- and cell-subtype-specific pattern. Particularly, intratelencephalic neurons (ITNs) showed earlier accumulation and greater extent of αSyn aggregates relative to corticospinal neurons (CSNs). Moreover, we demonstrated that the intrinsic excitability and inputs resistance of αSyn aggregates-bearing ITNs in the secondary motor cortex (M2) are increased, along with a noticeable shrinkage of cell bodies and loss of dendritic spines. Last, neither the intrinsic excitability of CSNs nor their thalamocortical input was altered by a partial striatal dopamine depletion associated with αSyn pathology. Our results documented motor cortical neuronal hyperexcitability associated with αSyn aggregation and provided a novel mechanistic understanding of cortical circuit dysfunction in PD.

8.
Food Res Int ; 192: 114751, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39147485

RESUMEN

This study employed a combination of principal component analysis (PCA) and gas chromatography-ion mobility spectrometry (GC-IMS) to examine the distinctive taste mixtures produced by Chinese spicy cabbage (CSC) fermented at varying temperatures. As the fermentation progressed, the pH gradually decreased and stabilized after the 11 days of fermentation, and the total content of organic acids and short-chain fatty acids increased. A total of 49 volatile mixtures were detected during CSC fermentation and storage for 21 days. These included 7 aldehydes, 6 alcohols, 7 esters, 6 ketones, 5 pyrazines, 4 sulfides, 4 phenols, 2 ethers, 2 olefins, and 1 acid. With time, the content of most volatile flavor substances decreased. PCA of the signal intensities of the volatile chemicals in the samples showed significant differences in the flavor of CSC fermented at different temperatures; consequently, the samples fermented at different temperatures were effectively separated in relatively independent regions of CSC. Therefore, low-temperature fermentation and storage at 4 °C were more suitable for CSC. Based on the identified volatile chemicals, HS-GC-IMS and PCA could effectively construct the flavour fingerprints of CSC samples. This study provided a theoretical basis for improving the fermentation quality of CSC.


Asunto(s)
Brassica , Fermentación , Análisis de Componente Principal , Gusto , Compuestos Orgánicos Volátiles , Brassica/química , Brassica/microbiología , Ácidos Grasos Volátiles/análisis , Cromatografía de Gases y Espectrometría de Masas , Concentración de Iones de Hidrógeno , Espectrometría de Movilidad Iónica , Temperatura , Compuestos Orgánicos Volátiles/análisis
9.
Chem Commun (Camb) ; 60(71): 9530-9533, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39145466

RESUMEN

A durable and efficient hydrophobic/superoleophilic MIL-88A(Fe)@sponge (MS) with high throughput was fabricated via the dip-coating technique. Its adsorption capacities for pump oil, peanut oil, and CCl4 were 32.13 g g-1, 34.85 g g-1, and 34.25 g g-1, respectively. The hydrophobic surface of MS has excellent chemical resistance and physical stability in harsh environments.

10.
Sci Rep ; 14(1): 17703, 2024 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-39085289

RESUMEN

Renal interstitial fibrosis (RIF) is a prevalent consequence of chronic renal diseases, characterized by excessive extracellular matrix (ECM) deposition. A Disintegrin and Metalloprotease 17 (ADAM17), a transmembrane metalloproteinase, plays a central role in driving renal fibrosis progression by activating Notch 1 protein and the downstream TGF-ß signaling pathway. Our study investigated potential therapeutic interventions for renal fibrosis, focusing on human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs). We found that hucMSC-EVs inhibit ADAM17, thereby impeding renal fibrosis progression. Analysis of hucMSC-EVs miRNA profiles revealed significant enrichment of miR-13474, which effectively targeted and inhibited ADAM17 mRNA expression, subsequently suppressing Notch1 activation, TGF-ß signaling, and collagen deposition. Overexpression of miR-13474 enhanced hucMSC-EVs' inhibitory effect on renal fibrosis, while its downregulation abolished this protective effect. Our findings highlight the efficacy of hucMSC-EVs overexpressing miR-13474 in mitigating renal fibrosis via ADAM17 targeting. These insights offer potential therapeutic strategies for managing renal fibrosis.


Asunto(s)
Proteína ADAM17 , Vesículas Extracelulares , Fibrosis , Riñón , Células Madre Mesenquimatosas , MicroARNs , MicroARNs/genética , MicroARNs/metabolismo , Proteína ADAM17/metabolismo , Proteína ADAM17/genética , Humanos , Vesículas Extracelulares/metabolismo , Células Madre Mesenquimatosas/metabolismo , Animales , Riñón/metabolismo , Riñón/patología , Transducción de Señal , Enfermedades Renales/metabolismo , Enfermedades Renales/terapia , Enfermedades Renales/patología , Enfermedades Renales/genética , Factor de Crecimiento Transformador beta/metabolismo , Ratones
11.
bioRxiv ; 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38948850

RESUMEN

Decreased excitability of pyramidal tract neurons in layer 5B (PT5B) of primary motor cortex (M1) has recently been shown in a dopamine-depleted mouse model of parkinsonism. We hypothesized that decreased PT5B neuron excitability would substantially disrupt oscillatory and non-oscillatory firing patterns of neurons in layer 5 (L5) of primary motor cortex (M1). To test this hypothesis, we performed computer simulations using a previously validated computer model of mouse M1. Inclusion of the experimentally identified parkinsonism-associated decrease of PT5B excitability into our computational model produced a paradoxical increase in rest-state PT5B firing rate, as well as an increase in beta-band oscillatory power in local field potential (LFP). In the movement-state, PT5B population firing and LFP showed reduced beta and increased high-beta, low-gamma activity of 20-35 Hz in the parkinsonian, but not in control condition. The appearance of beta-band oscillations in parkinsonism would be expected to disrupt normal M1 motor output and contribute to motor activity deficits seen in patients with Parkinson's disease (PD).

12.
Cereb Cortex ; 34(7)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-39066504

RESUMEN

The cerebral cortex has long been thought to be involved in the pathophysiology of motor symptoms of Parkinson's disease. The impaired cortical function is believed to be a direct and immediate effect of pathologically patterned basal ganglia output, mediated to the cerebral cortex by way of the ventral motor thalamus. However, recent studies in humans with Parkinson's disease and in animal models of the disease have provided strong evidence suggesting that the involvement of the cerebral cortex is much broader than merely serving as a passive conduit for subcortical disturbances. In the present review, we discuss Parkinson's disease-related changes in frontal cortical motor regions, focusing on neuropathology, plasticity, changes in neurotransmission, and altered network interactions. We will also examine recent studies exploring the cortical circuits as potential targets for neuromodulation to treat Parkinson's disease.


Asunto(s)
Corteza Motora , Enfermedad de Parkinson , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/patología , Humanos , Corteza Motora/fisiopatología , Animales , Plasticidad Neuronal/fisiología , Vías Nerviosas/fisiopatología
13.
J Environ Manage ; 366: 121785, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38981275

RESUMEN

Clearly delineating the key capabilities of organizational resilience for fisheries enterprises holds significant practical implications, as it can mitigate financing risks and foster the sustainable development of the fisheries industry. Based on the "dynamic capabilities perspective", this study constructs an analytical framework for the resilience capabilities of fisheries enterprises against financing risk. A hybrid method comprising the probabilistic linguistic term set, the decision-making trial and evaluation laboratory, and the additive ratio assessment is applied to a case study of Homey Group, examining the diverse pathways through which financing risk forms and impacts outcomes. The main findings are: (1) In the comprehensive assessment of the role of resilience capabilities in addressing the "Risk-Seeking-Decline Type" financing risk factors, market diversification and sustainable practices are accorded higher weights surpassing financial resources as the two most value-enhancing resilience capabilities. Enterprises characterized by a "Risk-Seeking-Loss Type" profile tend to assign higher weights to market diversification and technological infrastructure when evaluating financing risk resilience capabilities. (2) Regarding the key capabilities of organizational resilience, Homey Group possesses a weak risk management system for monitoring and evaluating significant risks and implementing control activities. (3) With regards to suggestions for improvement, it is advisable to delegate oversight of the risk identification process to a designated risk committee or specialists in risk management. The conclusions contribute to a deeper understanding of the nature and mechanism of resilience capabilities for fisheries enterprises and provides implications for risk management and sustainable development.


Asunto(s)
Explotaciones Pesqueras , Explotaciones Pesqueras/economía , Gestión de Riesgos , Conservación de los Recursos Naturales , Desarrollo Sostenible
14.
STAR Protoc ; 5(3): 103140, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-38905103

RESUMEN

Here we present an open-source behavioral platform and software solution for studying fine motor skills in mice performing reach-to-grasp task. We describe steps for assembling the box, training mice to perform the task, and processing the video with the custom software pipeline to analyze forepaw kinematics. The behavioral platform uses readily available and 3D-printed components and was designed to be affordable and universally reproducible. We provide the schematics, 3D models, code, and assembly instructions in the open GitHub repository.


Asunto(s)
Miembro Anterior , Movimiento , Programas Informáticos , Animales , Ratones , Miembro Anterior/fisiología , Fenómenos Biomecánicos/fisiología , Movimiento/fisiología , Destreza Motora/fisiología
15.
MMWR Morb Mortal Wkly Rep ; 73(23): 529-533, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38870469

RESUMEN

High-quality vaccine-preventable disease (VPD) surveillance data are critical for timely outbreak detection and response. In 2019, the World Health Organization (WHO) African Regional Office (AFRO) began transitioning from Epi Info, a free, CDC-developed statistical software package with limited capability to integrate with other information systems, affecting reporting timeliness and data use, to District Health Information Software 2 (DHIS2). DHIS2 is a free and open-source software platform for electronic aggregate Integrated Disease Surveillance and Response (IDSR) and case-based surveillance reporting. A national-level reporting system, which provided countries with the option to adopt this new system, was introduced. Regionally, the Epi Info database will be replaced with a DHIS2 regional data platform. This report describes the phased implementation from 2019 to the present. Phase one (2019-2021) involved developing IDSR aggregate and case-based surveillance packages, including pilots in the countries of Mali, Rwanda, and Togo. Phase two (2022) expanded national-level implementation to 27 countries and established the WHO AFRO DHIS2 regional data platform. Phase three (from 2023 to the present) activities have been building local capacity and support for country reporting to the regional platform. By February 2024, eight of 47 AFRO countries had adopted both the aggregate IDSR and case-based surveillance packages, and two had successfully transferred VPD surveillance data to the AFRO regional platform. Challenges included limited human and financial resources, the need to establish data-sharing and governance agreements, technical support for data transfer, and building local capacity to report to the regional platform. Despite these challenges, the transition to DHIS2 will support efficient data transmission to strengthen VPD detection, response, and public health emergencies through improved system integration and interoperability.


Asunto(s)
Vigilancia de la Población , Programas Informáticos , Enfermedades Prevenibles por Vacunación , Organización Mundial de la Salud , Humanos , África/epidemiología , Enfermedades Prevenibles por Vacunación/prevención & control , Enfermedades Prevenibles por Vacunación/epidemiología
16.
Nat Commun ; 15(1): 3900, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724552

RESUMEN

By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC+ mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus. Additionally, we find ITLN-1 protein binds the C-terminus of the MUC5AC mucin and that its deletion in airway epithelial cells partially reverses IL-13-induced mucostasis. Through analysis of nasal airway epithelial brushings, we find that ITLN1 is highly expressed in T2-high asthmatics, when compared to T2-low children. Furthermore, we demonstrate that both ITLN-1 gene expression and protein levels are significantly reduced by a common genetic variant that is associated with protection from the formation of mucus plugs in T2-high asthma. This work identifies an important biomarker and targetable pathways for the treatment of mucus obstruction in asthma.


Asunto(s)
Asma , Proteínas Ligadas a GPI , Interleucina-13 , Lectinas , Mucina 5AC , Moco , Niño , Humanos , Asma/genética , Asma/metabolismo , Citocinas , Células Epiteliales/metabolismo , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Interleucina-13/genética , Interleucina-13/metabolismo , Lectinas/genética , Lectinas/metabolismo , Mucina 5AC/genética , Mucina 5AC/metabolismo , Moco/metabolismo , Mucosa Nasal/metabolismo , Polimorfismo Genético , Mucosa Respiratoria/metabolismo
17.
J Hazard Mater ; 472: 134420, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38691997

RESUMEN

In this work, MIL-88A(Fe) was immobilized onto the expanded perlites to fabricate the floating MIL-88A(Fe)@expanded perlites (M@EP) catalyst via high throughput batch synthesis method under room temperature. The as-prepared M@EP could efficiently activate H2O2 to achieve 100% tetracycline antibiotics (TCs) removal under both artificial low power UV light (UVL) and real sunlight (SL) irradiation. The toxicological evaluation, growth experiment of mung beans and antimicrobial estimation revealed the decreasing aquatic toxicity of the TCs intermediates compared to those of the pristine TCs. A self-designed continuous bed reactor was employed to investigate the long-term operation of the M@EP. The findings demonstrated that the antibiotics mixture can be continuously degraded up to 7 days under UVL and 5 daytimes under SL irradiation, respectively. More importantly, ca. 76.9% and 81.6% of total organic carbon (TOC) removal efficiencies were accomplished in continuous bed reactor under UVL and SL irradiation, respectively. This work advances the immobilized MOFs on floating supports for their practical application in large-scale wastewater purification through advanced oxidation processes. ENVIRONMENTAL IMPLICATION: This work presented the high throughput production and photo-Fenton degradation application of floating MIL-88A(Fe)@expanded perlites (M@EP). Three tetracycline antibiotics (TCs) were selected as model pollutants to test the degradation ability of M@EP in batch experiment and continuous operation under artificial light and solar light. The complete TCs degradation could be accomplished in self-designed device up to 7 d under UV light and 5 d under real solar light. This work tapped a new door to push MOFs-based functional materials in the real water purification.

18.
Respir Res ; 25(1): 193, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702733

RESUMEN

BACKGROUND: Influenza A virus (IAV) infection is a significant risk factor for respiratory diseases, but the host defense mechanisms against IAV remain to be defined. Immune regulators such as surfactant protein A (SP-A) and Toll-interacting protein (Tollip) have been shown to be involved in IAV infection, but whether SP-A and Tollip cooperate in more effective host defense against IAV infection has not been investigated. METHODS: Wild-type (WT), Tollip knockout (KO), SP-A KO, and Tollip/SP-A double KO (dKO) mice were infected with IAV for four days. Lung macrophages were isolated for bulk RNA sequencing. Precision-cut lung slices (PCLS) from WT and dKO mice were pre-treated with SP-A and then infected with IAV for 48 h. RESULTS: Viral load was significantly increased in bronchoalveolar lavage (BAL) fluid of dKO mice compared to all other strains of mice. dKO mice had significantly less recruitment of neutrophils into the lung compared to Tollip KO mice. SP-A treatment of PCLS enhanced expression of TNF and reduced viral load in dKO mouse lung tissue. Pathway analysis of bulk RNA sequencing data suggests that macrophages from IAV-infected dKO mice reduced expression of genes involved in neutrophil recruitment, IL-17 signaling, and Toll-like receptor signaling. CONCLUSIONS: Our data suggests that both Tollip and SP-A are essential for the lung to exert more effective innate defense against IAV infection.


Asunto(s)
Virus de la Influenza A , Ratones Endogámicos C57BL , Ratones Noqueados , Infecciones por Orthomyxoviridae , Proteína A Asociada a Surfactante Pulmonar , Animales , Proteína A Asociada a Surfactante Pulmonar/metabolismo , Proteína A Asociada a Surfactante Pulmonar/genética , Ratones , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virología , Infecciones por Orthomyxoviridae/metabolismo , Virus de la Influenza A/inmunología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/virología
19.
Environ Toxicol Chem ; 43(7): 1557-1568, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38695729

RESUMEN

Persistent organic pollutants pose a great threat to amphibian populations, but information on the bioaccumulation of contaminants in amphibians remains scarce. To examine the tissue distribution and maternal transfer of organic halogenated pollutants (OHPs) in frogs, seven types of tissues from black-spotted frog (muscle, liver, kidney, stomach, intestine, heart, and egg) were collected from an e-waste-polluted area in South China. Among the seven frog tissues, median total OHP concentrations of 2.3 to 9.7 µg/g lipid weight were found (in 31 polychlorinated biphenyl [PCB] individuals and 15 polybrominated diphenyl ether [PBDE], dechlorane plus [syn-DP and anti-DP], bexabromobenzene [HBB], polybrominated biphenyl] PBB153 and -209], and decabromodiphenyl ethane [DBDPE] individuals). Sex-specific differences in contaminant concentration and compound compositions were observed among the frog tissues, and eggs had a significantly higher contaminant burden on the whole body of female frogs. In addition, a significant sex difference in the concentration ratios of other tissues to the liver was observed in most tissues except for muscle. These results suggest that egg production may involve the mobilization of other maternal tissues besides muscle, which resulted in the sex-specific distribution. Different parental tissues had similar maternal transfer mechanisms; factors other than lipophilicity (e.g., molecular size and proteinophilic characteristics) could influence the maternal transfer of OHPs in frogs. Environ Toxicol Chem 2024;43:1557-1568. © 2024 SETAC.


Asunto(s)
Contaminantes Orgánicos Persistentes , Animales , Femenino , Distribución Tisular , Masculino , Contaminantes Orgánicos Persistentes/metabolismo , Monitoreo del Ambiente , Éteres Difenilos Halogenados/metabolismo , Anuros/metabolismo , China , Ranidae/metabolismo , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/análisis
20.
eNeuro ; 11(5)2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38658137

RESUMEN

The primary motor cortex (M1) integrates sensory and cognitive inputs to generate voluntary movement. Its functional impairments have been implicated in the pathophysiology of motor symptoms in Parkinson's disease (PD). Specifically, dopaminergic degeneration and basal ganglia dysfunction entrain M1 neurons into the abnormally synchronized bursting pattern of activity throughout the cortico-basal ganglia-thalamocortical network. However, how degeneration of the midbrain dopaminergic neurons affects the anatomy, microcircuit connectivity, and function of the M1 network remains poorly understood. The present study examined whether and how the loss of dopamine (DA) affects the morphology, cellular excitability, and synaptic physiology of Layer 5 parvalbumin-expressing (PV+) cells in the M1 of mice of both sexes. Here, we reported that loss of midbrain dopaminergic neurons does not alter the number, morphology, and physiology of Layer 5 PV+ cells in M1. Moreover, we demonstrated that the number of perisomatic PV+ puncta of M1 pyramidal neurons as well as their functional innervation of cortical pyramidal neurons were not altered following the loss of DA. Together, the present study documents an intact GABAergic inhibitory network formed by PV+ cells following the loss of midbrain dopaminergic neurons.


Asunto(s)
Neuronas Dopaminérgicas , Interneuronas , Mesencéfalo , Corteza Motora , Parvalbúminas , Animales , Femenino , Masculino , Ratones , Neuronas Dopaminérgicas/metabolismo , Neuronas GABAérgicas/metabolismo , Interneuronas/metabolismo , Mesencéfalo/metabolismo , Ratones Endogámicos C57BL , Ratones Transgénicos , Corteza Motora/metabolismo , Inhibición Neural/fisiología , Parvalbúminas/metabolismo
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