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1.
Bioact Mater ; 21: 284-298, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36157247

RESUMO

It is of great importance to treat a bacterial-infected wound by a smart dressing capable of delivering antibiotics in a smart manner without causing drug resistance. The construction of smart release nanocontainers responsive to near-infrared (NIR) laser irradiation in an on-demand and stepwise way is a promising strategy for avoiding the emergence of multidrug-resistant bacteria. Here, we develop a hydrogel composite made of alginate and nanotubes with an efficient NIR-triggered release of rifampicin and outstanding antibacterial ability. This composite hydrogel is prepared through co-encapsulating antibacterial drug (rifampicin), NIR-absorbing dye (indocyanine green), and phase-change materials (a eutectic mixture of fatty acids) into halloysite nanotubes, followed by incorporation into alginate hydrogels, allowing the in-situ gelation at room temperature and maintaining the integrity of drug-loaded nanotubes. Among them, the eutectic mixture with a melting point of 39 °C serves as the biocompatible phase-change material to facilitate the NIR-triggered drug release. The resultant phase-change material gated-nanotubes exhibit a prominent photothermal efficiency with multistep drug release under laser irradiation. In an in vitro assay, composite hydrogel provides good antibacterial potency against Staphylococcus aureus, one of the most prevalent microorganisms of dangerous gas gangrene. A bacterial-infected rat full-thickness wound model demonstrates that the NIR-responsive composite hydrogel inhibits the bacteria colonization and suppresses the inflammatory response caused by bacteria, promoting angiogenesis and collagen deposition to accelerate wound regeneration. The NIR-responsive composite hydrogel has a great potential as an antibacterial wound dressing functionalized with controlled multistep treatment of the infected sites.

2.
J Theor Biol ; 556: 111310, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36279959

RESUMO

Midbrain dopamine (DA) neurons exhibit spiking and bursting patterns under physiological conditions. Based on the data on electrophysiological recordings, Yu et al. developed a 13-dimensional mathematical model to capture the detailed characteristics of the DA neuronal firing activities. We use the fitting method to simplify the original model into a 4-dimensional model. Then, the spiking-to-bursting transition is detected from a simple and robust mathematical condition. Physiologically, this condition is a balance of the restorative and the regenerative ion channels at resting potential. Geometrically, this condition imposes a transcritical bifurcation. Moreover, we combine singularity theory and singular perturbation methods to capture the geometry of three-timescale firing attractors in a universal unfolding of a cusp singularity. In particular, the planar description of the corresponding firing patterns can generate the corresponding firing attractors. This analysis provides a new idea for understanding the firing activities of the DA neuron and the specific mechanisms for the switching and dynamic regulation among different patterns.


Assuntos
Dopamina , Mesencéfalo , Potenciais de Ação/fisiologia , Mesencéfalo/fisiologia , Neurônios Dopaminérgicos/fisiologia , Potenciais da Membrana
3.
Sci Total Environ ; 857(Pt 1): 159305, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36216056

RESUMO

BACKGROUND: Epidemiological evidence reported that particulate matter (PM) was associated with increased schizophrenia (SCZ) risk. Disturbance of gut microbiome was involved in SCZ. However, it remains unclear whether PM induces SCZ-like symptoms and how gut microbiome regulates them. Therefore, a multi-omics animal experiment was conducted to verify how urban PM induces SCZ-like behavior and altered gut microbiota and metabolic pathways. METHODS: Using a completely random design, mice were divided into three groups: PM group, control group and MK801 group, which received daily tracheal instillation of PM solution, sterile PBS solution and intraperitoneal injection of MK801 (establish SCZ model), respectively. After a 14-day intervention, feces were collected for multi-omics testing (shotgun metagenomic sequencing and untargeted metabolomic profiling), followed by open field test, tail suspension test, and passive avoidance test. Besides, fecal microbiome of PM group and control group were transplanted into "pseudo-sterile" mice, then behavioral tests were conducted. RESULTS: Similar to MK801 group, mice in PM group showed SCZ-like symptoms, including increased spontaneous activity, excitability, anxiety and decreased learning and spatial memory. PM exposure significantly increased the relative abundance of Verrucomicrobia and decreased that of Fibrobacteres et al. The metabolism pathways of estrogen signaling (estriol, 16-glucuronide-estriol and 21-desoxycortisol) and choline metabolism (phosphocholine) were significantly altered by PM exposure. Verrucomicrobia was negatively correlated with the level of estriol, which was correlated with decreased learning and spatial memory. Fibrobacteres and Deinococcus-Thermus were positively correlated with the level of phosphocholine, which was correlated with increased spontaneous activity, excitability and anxiety. Fecal microbiome transplantation from PM group mice reproduced excitability and anxiety symptoms. CONCLUSIONS: Exposure to PM may affect composition of gut microbiome and alterations of estrogen signaling pathway and choline metabolism pathway, which were associated with partial SCZ-like behaviors. But whether gut microbiome regulates these metabolic pathways and behaviors remains to be determined.


Assuntos
Microbioma Gastrointestinal , Esquizofrenia , Animais , Camundongos , Material Particulado/toxicidade , Maleato de Dizocilpina/farmacologia , Fosforilcolina/farmacologia , Fezes , Estriol , Estrogênios , RNA Ribossômico 16S
4.
Food Chem ; 402: 134265, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36179521

RESUMO

In this study, yeast and soy protein at different ratios (0:1, 1:9, 2:8, 3:7, 4:6, and 5:5) were used to produce meat analogues (MA) via high-moisture extrusion. According to color analysis, the addition of yeast protein (YP) increased the lightness of MA from 43.12 ± 0.26 (the control) to 50.37 ± 0.46 (50 g/100 g, dry basis). Textural results indicated that when the YP content was 40 g/100 g (dry basis), the hardness, chewiness, and fibrous degree of MA reached the maximum (523.94 ± 11.91 N, 724.55 ± 22.89 N, and 2.06 ± 0.15, respectively), which were higher than the control (419.63 ± 7.52 N, 618.02 ± 14.82 N, and 1.43 ± 0.03, respectively). Furthermore, YP increased the free water ratio, SS bond, and total ß-sheets structure content, while reducing the ß-turn structure content and thermal stability of MA. Overall, YP is a promising protein source for preparing high-quality MA.


Assuntos
Saccharomyces cerevisiae , Proteínas de Soja , Proteínas de Soja/análise , Manipulação de Alimentos , Carne/análise , Água
5.
Artigo em Inglês | MEDLINE | ID: mdl-36316554

RESUMO

Stimulating indigenous microbes to reduce aqueous U(VI) to insoluble U(IV) by adding an electron donor has been applied as an applicable strategy to remediate uranium-contaminated groundwater in situ. However, biogenic U(IV) minerals are susceptible to oxidative remobilization after exposure to oxygen. To enhance the stability of the end product, glycerol phosphate (GP) was selected to treat artificial uranium-containing groundwater at different pH values (i.e., 7.0 and 5.0) with glycerol (GY) as the control group. The results revealed that removal ratios of uranium with GP were all higher than those with GY, and reduced crystalline U(IV)-phosphate and U(VI)-phosphate minerals (recalcitrant to oxidative remobilization) were generated in the GP groups. Although bioreduction efficiency was influenced at pH 5.0, the stability of the end product with GP was elevated significantly compared with that with GY. Mechanism analysis demonstrated that GP could activate bioreduction and biomineralization of the microbial community, and two stages were included in the GP groups. In the early stage, bioreduction and biomineralization were both involved in the immobilization process. Subsequently, part of the U(VI) precipitate was gradually reduced to U(IV) precipitate by microorganisms. This work implied that the formation of U-phosphate minerals via bioreduction coupled with biomineralization potentially offers a more effective strategy for remediating uranium-contaminated groundwater with long-term stability.

6.
Water Environ Res ; 94(11): e10812, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36433882

RESUMO

In this study, biogas and biogas slurry were simultaneously treated using two symbiotic systems: Chlorella vulgaris-Ganoderma lucidum-S395-2 (endophytic bacteria) and Scenedesmus obliquus-G. lucidum-S395-2. The influence of different mixed illumination (red and blue) intensity ratios on the algal symbionts' extracellular carbonic anhydrase activities was investigated, as well as the rates of microalgal growth and photosynthesis. The treatment performance was simultaneously assessed in terms of the efficiency of organic matter or nutrient removal and the level of CO2 absorption. The results indicated that red-blue light combinations with an intensity ratio of 5:5 were optimal. When comparing the performance of the two symbiotic systems, the C. vulgaris-G. lucidum-S395-2 symbiont co-culture system achieved significantly improved photosynthetic rates, biomass growth, and treatment effects. Under the optimal treatment conditions, the organic matter and nutrient removal rates were 81.06% ± 7.06% for chemical oxygen demand, 82.32% ± 7.18% for total nitrogen, and 82.98% ± 7.26% for total phosphorus. In addition, the rate of CO2 removal from biogas was 63.38% ± 5.35%. PRACTITIONER POINTS: The red and blue light intensity ratio of 5:5 showed the best removal performance. C. vulgaris-G. lucidum-S395-2 system obtained the best photosynthetic performance. The carbonic anhydrase activity had positive effects on CO2 removal performance.

7.
Front Immunol ; 13: 1013542, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36420261

RESUMO

Head and neck squamous cell carcinoma (HNSCC) usually has a poor prognosis and is associated with a high mortality rate. Its etiology is mainly the result from long-term exposure to either alcohol, tobacco or human papillomavirus (HPV) infection or a combination of these insults. However, HNSCC patients with HPV have been found to show a survival advantage over those without the virus, but the mechanism that confers this advantage is unclear. Due to the large number of HPV-independent HNSCC cases, there is a possibility that the difference in prognosis between HPV-positive (HPV+) and negative (HPV-) patients is due to different carcinogens. To clarify this, we used scRNA data and viral tracking methods in order to identify HPV+ and HPV- cells in the tumour tissues of patients infected with HPV. By comparing HPV+ and HPV- malignant cells, we found a higher level of tumour stemness in HPV- tumour cells. Using tumour stemness-related genes, we established a six-gene prognostic signature that was used to divide the patients into low- and high-risk groups. It was found that HPV patients who were at low-risk of contracting HNSCC had a higher number of CD8+ T-cells as well as a higher expression of immune checkpoint molecules. Correspondingly, we found that HPV+ tumour cells expressed higher levels of CCL4, and these were highly correlated with CD8+ T cells infiltration and immune checkpoint molecules. These data suggest that the stemness features of tumour cells are not only associated with the prognostic risk, but that it could also affect the immune cell interactions and associated signalling pathways.


Assuntos
Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Linfócitos T CD8-Positivos , Papillomaviridae , Proteínas de Checkpoint Imunológico
8.
Fitoterapia ; 163: 105343, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36328169

RESUMO

In this study, it was confirmed at first time that the crude extracts of Psoralea corylifolia seeds (PCE34) can reduce serum lipids (AST, ALT, TG, TC, LDL, ALP, ACP and LDH), body weight and serum sugar, increase HDL and serum insulin in hyperlipidemic wistar rat induced by high-fat diet in vivo. Furthermore, eight new chalcones 1-8, one new flavanone 12, one new coumarin 14, three new meroterpenes 15-17 and one new bakuchiol 20 together with seven known compounds (9-11, 13, 18-19 and 21) were isolated from the PCE34. Their structures were elucidated based on analyses of their spectroscopic (UV, CD, NMR and HREIMS) data. All the isolates were evaluated for in vitro inhibitory activity against DGAT1/2, PTP1B and α-Glucosidase. Among them, compounds 1-3, 8-11, 14-17, 19 and 20 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 66.7 ± 1.2 to 87.2 ± 1.3 µM; 1, 8-12, 14 and 20 has the best inhibit active on PTP1B with IC50 values ranging from 13.8 ± 1.1 to 19.1 ± 1.6 µM; 1-12 and 14 displayed the significant inhibitory activities on α-Glucosidase with IC50 values ranging from 29.1 ± 1.2 to 79.4 ± 1.2 µM.

9.
Sci Total Environ ; 858(Pt 2): 159829, 2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36374752

RESUMO

BACKGROUND: Frail individuals often face a high medical burden, and household solid fuel use is associated with a range of functional declines or diseases, but evidence on the relationship between household solid fuel and frailty and the resulting medical burden is limited. We aim to investigate the effect of household solid fuel on frailty and further quantify how much of the increased medical burden associated with frailty is attributable to household solid fuel. METHODS: The prospective data were from the China Health and Retirement Longitudinal Study, 4685 non-frail participants at baseline were included. Inverse probability weighting was used to balance the covariates between groups. The modified Poisson regression was used to analyze the association of household solid fuel (including baseline and switching across three-wave survey) with frailty, and the generalized linear model was used to analyze the association of frailty with the change in medical burden. Further, the increased medical burden associated with frailty attributable to household solid fuel was quantified. RESULTS: Using solid fuel for cooking (RR = 1.29, 95%CI, 1.07-1.57), heating (RR = 1.38, 95%CI, 1.09-1.73), or both (RR = 1.40, 95%CI, 1.05-1.86) had a higher risk of frailty than using clean fuel. In addition, the risk of frailty generally increases with the times of solid fuel use across the three-wave survey. Then, frailty participants had a greater increase in the annual number of hospitalizations (ß = 0.11, 95%CI, 0.02-0.19) and annual costs of hospitalizations (ß = 2953.35, 95%CI, 1149.87-4756.83) than those non-frailty. Heating coal caused the largest frailty-related increase in the annual number of hospitalizations and annual costs of hospitalizations, with 0.04 and 1195.40, respectively. CONCLUSION: The increased medical burden associated with frailty was partly attributable to household solid fuel, which suggested that intervention targeting household solid fuels can delay frailty and thus reduce individual medical burden.

10.
Int Heart J ; 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36372406

RESUMO

Epicardial adipose tissue (EAT) and pericardial adipose tissue (PAT) are anatomically close to the myocardium and may influence cardiovascular pathology. Thus, in this study, we aim to assess whether EAT and PAT volumes were associated with coronary artery calcification score (CCS) in patients with suspected coronary artery disease (CAD), especially in overweight and obese individuals.We included consecutive patients with suspected CAD in whom EAT volume, PAT volume, and CCS were measured via computed tomography between September 2015 and June 2017 at the Affiliated Hospital of Chengde Medical University, China. Logistic regression models were applied to analyze the risk factors for CCS ≥ 100 Agatston units (AU) and in different body mass index (BMI) subgroups.EAT and PAT volumes were noted to be higher in people with BMI ≥ 24 kg/m2, BMI ≥ 28 kg/m2, hyperlipidemia, hypertension, diabetes, stroke, and CCS ≥ 100 AU (P < 0.05). After adjusting for the traditional CAD factors, we found that EAT and PAT volumes were independent risk factors for CCS ≥ 100 AU (odds ratio, 3.001; 95% confidence interval, 1.900-4.740, P < 0.001). In patients with CCS ≥ 100 AU, the EAT and PAT volumes were noted to be greater in the BMI ≥ 24 kg/m2 and BMI ≥ 28 kg/m2 subgroups than in the BMI < 24 kg/m2 and BMI < 28 kg/m2 subgroups, respectively (P < 0.05).Our results indicate that EAT and PAT volumes may be clinical predictors for a CCS ≥ 100 AU, especially in overweight and obese individuals.

11.
BMC Med Genomics ; 15(1): 230, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329483

RESUMO

BACKGROUND: Waardenburg syndrome (WS) is the most common form of syndromic deafness with phenotypic and genetic heterogeneity in the Chinese population. This study aimed to clarify the clinical characteristics and the genetic cause in eight Chinese WS families (including three familial and five sporadic cases). Further genotype-phenotype relationships were also investigated. METHODS: All probands underwent screening for the known WS-related genes including PAX3, SOX10, MITF, EDNRB, EDN3, and SNAI2 using next-generation sequencing to identify disease-causing genes. Further validation using Sanger sequencing was performed. Relevant findings for the associated genotype-phenotype from previous literature were retrospectively analyzed. RESULT: Disease-causing variants were detected in all eight probands by molecular genetic analysis of the WS genes (SOX10(NM_006941.4): c.544_557del, c.553 C > T, c.762delA, c.336G > A; MITF(NM_000248.3): c.626 A > T; PAX3(NM_181459.4): c.838delG, c.452-2 A > G, c.214 A > G). Six mutations (SOX10:c.553 C > T, c.544_557del, c.762delA; PAX3: c.838delG, c.214 A > G; MITF:c.626 A > T) were first reported. Clinical evaluation revealed prominent phenotypic variability in these WS patients. Twelve WS1 cases and five WS2 cases were diagnosed in total. Two probands with SOX10 mutations developed progressive changes in iris color with age, returning from pale blue at birth to normal tan. Additionally, one proband had a renal malformation (horseshoe kidneys).All cases were first described as WS cases. Congenital inner ear malformations were more common, and semicircular malformations were exclusively observed in probands with SOX10 mutations. Unilateral hearing loss occurred more often in cases with PAX3 mutations. CONCLUSION: Our findings helped illuminate the phenotypic and genotypic spectrum of WS in Chinese populations and could contribute to better genetic counseling of WS.


Assuntos
Síndrome de Waardenburg , Humanos , Síndrome de Waardenburg/genética , Síndrome de Waardenburg/diagnóstico , Estudos Retrospectivos , Linhagem , Fatores de Transcrição SOXE/genética , Genótipo , Mutação , Fenótipo , China
13.
Nanomaterials (Basel) ; 12(22)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36432256

RESUMO

In the present work, a facile one-step methodology was used to synthesize honeycomb-like BiFeO3/g-C3N4 composites, where the well-dispersed BiFeO3 strongly interacted with the hg-C3N4. The 10BiFeO3/hg-C3N4 could completely degrade RhB under visible light illumination within 60 min. The degradation rate constant was remarkably improved and approximately three times and seven times that of pristine hg-C3N4 and BiFeO3, respectively. This is ascribed to the following factors: (1) the unique honeycomb-like morphology facilitates the diffusion of the reactants and effectively improves the utilization of light energy by multiple reflections of light; (2) the charged dye molecules can be tightly bound to the spontaneous polarized BiFeO3 surface to form the Stern layer; (3) the Z-scheme heterojunction and the ferroelectric synergistically promoted the efficient separation and migration of the photogenerated charges. This method can synchronously tune the micro-nano structure, surface property, and internal field construction for g-C3N4-based photocatalysts, exhibiting outstanding potential in environmental purification.

14.
J Ethnopharmacol ; : 115954, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36435409

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic ulcers (DUs) are one of the most severe complications of diabetes, and efficacious therapeutic means are currently lacking. Sheng-ji Hua-yu (SJHY) ointment is a classical Chinese traditional prescription that can significantly attenuate DU defects, but the specific mechanism remains to be fully elucidated. AIM OF THE STUDY: In order to verify the underlying mechanism of SJHY ointment in accelerating the closure of DUs. MATERIALS AND METHODS: Modular pharmacology and molecular docking were utilized to predict the therapeutic targets of SJHY ointment against DUs. Male db/db diabetic mice and HaCaT cell models induced by methylglyoxal were used to validate the findings. RESULTS: CCN1 was proven to be the core target of SJHY ointment involved in DUs treatment. CCN1 up-regulated by SJHY treatment (0.5 g/cm2/day) at the mRNA and protein levels were detected on Day 9 after wounding. When CCN1 knockdown, accelerated cell proliferation, migration, and anti-inflammatory effect of SJHY treatment (10 mg/L) were reversed. CONCLUSIONS: SJHY ointment ameliorates cutaneous wound healing by up-regulating CCN1.

15.
Eur J Med Chem ; 245(Pt 1): 114898, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36370552

RESUMO

50 New drugs including 36 chemical entities and 14 biologics were approved by the U.S. Food and Drug Administration during 2021. Among the marketed drugs, 31 new small molecule agents (29 small molecule drugs and 2 diagnostic agents) with privileged structures and novel clinical applications represent as promising leads for the development of new drugs with the similar indications and improved therapeutic efficacy. This review is mainly focused on the clinical applications and synthetic methods of 29 small molecule drugs newly approved by the FDA in 2021. We believed that insight into the synthetic approaches of drug molecules would provide creative and practical inspirations for the development of more efficient and practical synthetic technologies to meet with new drug discovery.

16.
Environ Int ; 170: 107605, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36323064

RESUMO

BACKGROUND: More studies focus on reporting the effects of ambient air pollution on physical activity while ignoring the hazards of indoor air pollution caused by household solid fuel use. Moreover, the impact of individual cognitive and depressive status on the health effects of air pollution is often overlooked. OBJECTIVE: We examined the association between household solid fuel and activities of daily living (ADL) trajectories, and further examined this association in homogeneous subgroups of cognitive or depressive trajectories. METHODS: Participants were from the China Health and Retirement Longitudinal Study, which conducted four waves of surveys from 2011 to 2018. We collected information on participants' household fuel use, then the ADL, cognitive and depressive performances were assessed in each wave. The latent growth mixture model (LGMM) was used to identify the optimal trajectory class for ADL, cognition, and depression. Then, the multinomial logistic regression was used to assess the association between solid fuel use and ADL trajectories in total population, as well as subgroups with different cognitive or depression trajectories. Furthermore, we examined the association between switching household fuel types and ADL trajectories across the four-wave survey. RESULTS: The study sample included 7052 participants. We identified three ADL trajectory classes in total population: "Low-stable", "Moderate-anterior rise", and "Moderate-posterior rise". The multinomial logistic regression results showed that solid fuel use was associated with elevated odds for the adverse ADL trajectories, and this association was still shown in homogeneous subgroups of cognitive or depressive trajectories, while some effects were less significant. In addition, the risk of adverse ADL trajectories generally increases with the times of solid fuel use across the four-wave survey. CONCLUSIONS: For middle and older adults in China, household solid fuel use was not conducive to physical activity development, which inspires that a further transformation to cleaner fuels is an important intervention.

17.
Opt Express ; 30(12): 20859-20870, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-36224821

RESUMO

Highly emissive spaceborne blackbody radiation sources are important devices for infrared value traceability by providing accurate infrared radiation to calibrate infrared load. To meet the needs of the radiation calibration accuracy needed for infrared remote sensing, this paper proposes a highly emissive blackbody that uses cubic reflection and an absorption method based on light capture. An emissivity simulation based on ray tracing was carried out. The influences of specular reflection (SR), near specular reflection (NSR), and diffuse reflection (DR) on the emissivity of the blackbody were analyzed. Two blackbodies with NSR and DR were fabricated, simulated, and tested experimentally; the experimental and simulation results were consistent.

18.
Front Chem ; 10: 981173, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36238092

RESUMO

Mulberroside A is a polyhydroxylated stilbene active component of Morus alba L. Studies have shown that it has antitussive, antiasthmatic, tyrosinase and antioxidation activities. However, little is known about the metabolism of it in vitro and in vivo. In our study, an integrated strategy on the basis of UHPLC-Q-Exactive Plus Orbitrap MS and network pharmacology was established to comprehensively research the metabolic characteristic of mulberroside A for the first time. Plasma, urine, feces and liver tissues of rats in the blank group and drug group were collected after intragastric administration of mulberroside A at a dose of 150 mg/kg, and rat liver microsomes were cultured for in vitro metabolism experiment. The biological samples were processed by different methods and analyzed in positive and negative ion modes using UHPLC-Q-Exactive Plus Orbitrap MS. A total of 72 metabolites were finally identified based on the accurate molecular mass, retention time, MS/MS spectra and related literatures combined with the Compound Discoverer 3.1. The metabolic pathways were mainly hydrolysis, glucuronidation, hydrogenation, sulfation, hydroxylation, methylation and their composite reactions. In addition, a network pharmacology method was used to predict the mechanism of action of mulberroside A and its metabolites. In the end, 7 metabolites with high gastrointestinal absorption and drug-likeness and 167 targets were screened by Swiss ADME and Swiss Target Prediction. 1702 items of GO analysis and 158 related signaling pathways of KEGG were enriched using Metascape. This study established a novel integrated strategy based on UHPLC-Q-Exactive Plus Orbitrap MS and network pharmacology, which could systematically analyze the metabolism behavior of mulberroside A in vivo and in vitro of rats and provide basis for the further research of mulberroside A.

20.
Elife ; 112022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36197007

RESUMO

The blood-brain barrier (BBB) limits the entry of leukocytes and potentially harmful substances from the circulation into the central nervous system (CNS). While BBB defects are a hallmark of many neurological disorders, the cellular heterogeneity at the neurovascular interface, and the mechanisms governing neuroinflammation are not fully understood.Through single-cell RNA sequencing of non-neuronal cell populations of the murine cerebral cortex during development, adulthood, ageing, and neuroinflammation, we identify reactive endothelial venules, a compartment of specialized postcapillary endothelial cells that are characterized by consistent expression of cell adhesion molecules, preferential leukocyte transmigration, association with perivascular macrophage populations, and endothelial activation initiating CNS immune responses. Our results provide novel insights into the heterogeneity of the cerebral vasculature and a useful resource for the molecular alterations associated with neuroinflammation and ageing.


Assuntos
Células Endoteliais , Endotélio Vascular , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Moléculas de Adesão Celular/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Camundongos , Transcriptoma
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