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1.
Neural Regen Res ; 20(2): 557-573, 2025 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38819067

RESUMEN

JOURNAL/nrgr/04.03/01300535-202502000-00032/figure1/v/2024-05-28T214302Z/r/image-tiff Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury. Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction. However, the mechanisms involved remain unclear. In this study, we found that after spinal cord injury, resting microglia (M0) were polarized into pro-inflammatory phenotypes (MG1 and MG3), while resting astrocytes were polarized into reactive and scar-forming phenotypes. The expression of growth arrest-specific 6 (Gas6) and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury. In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia, and even inhibited the cross-regulation between them. We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway. This, in turn, inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways. In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord, thereby promoting tissue repair and motor function recovery. Overall, Gas6 may play a role in the treatment of spinal cord injury. It can inhibit the inflammatory pathway of microglia and polarization of astrocytes, attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment, and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

2.
Nat Commun ; 15(1): 6697, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107299

RESUMEN

The skeleton has been suggested to function as an endocrine organ controlling whole organism energy balance, however the mediators of this effect and their molecular links remain unclear. Here, utilizing Schnurri-3-/- (Shn3-/-) mice with augmented osteoblast activity, we show Shn3-/-mice display resistance against diet-induced obesity and enhanced white adipose tissue (WAT) browning. Conditional deletion of Shn3 in osteoblasts but not adipocytes recapitulates lean phenotype of Shn3-/-mice, indicating this phenotype is driven by skeleton. We further demonstrate osteoblasts lacking Shn3 can secrete cytokines to promote WAT browning. Among them, we identify a C-terminal fragment of SLIT2 (SLIT2-C), primarily secreted by osteoblasts, as a Shn3-regulated osteokine that mediates WAT browning. Lastly, AAV-mediated Shn3 silencing phenocopies the lean phenotype and augmented glucose metabolism. Altogether, our findings establish a novel bone-fat signaling axis via SHN3 regulated SLIT2-C production in osteoblasts, offering a potential therapeutic target to address both osteoporosis and metabolic syndrome.


Asunto(s)
Tejido Adiposo Blanco , Huesos , Dieta Alta en Grasa , Péptidos y Proteínas de Señalización Intercelular , Ratones Noqueados , Obesidad , Osteoblastos , Animales , Obesidad/metabolismo , Obesidad/genética , Obesidad/etiología , Tejido Adiposo Blanco/metabolismo , Osteoblastos/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Ratones , Dieta Alta en Grasa/efectos adversos , Huesos/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Masculino , Tejido Adiposo Pardo/metabolismo , Ratones Endogámicos C57BL , Adipocitos/metabolismo , Transducción de Señal
3.
PLoS One ; 19(8): e0308220, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39116065

RESUMEN

The oil used to fry food is often used multiple times to reduce costs. However, when foods containing sweeteners are processed in this way, the sweeteners may produce substances harmful to the body as a result of repeated frying at high temperatures. This article investigated the stability of sodium cyclamate during deep-frying by HPLC using a pre-column derivatization method. The results showed that cyclohexylamine was a decomposition product of a standard sample of sodium cyclamate when deep-fried at 200°C for 25 min. A pre-column derivatization/HPLC method was established to determine cyclohexylamine, a decomposition product of sodium cyclamate, under these conditions. Dansyl chloride was used as the derivatization reagent, the derivatization temperature was 60°C, the derivatization time was 20 min, the pH of sodium bicarbonate buffer solution was 11, and the concentration of dansyl chloride was 2.0 mg/mL. Detection was carried out by using an Agilent 1260 high-performance liquid chromatograph coupled with an ultraviolet detector. The ultraviolet detection wavelength was 254 nm, and the mobile phase was acetonitrile-1.0 g/L potassium dihydrogen phosphate solution at a flow rate of 1.0 mL/min. Gradient elution was adopted, the peak of the cyclohexylamine derivative appeared at a retention time of 17.75 min, and the peak area response value was the largest. The methodological validation analysis showed that the detection limit of cyclohexylamine was 0.5 mg/kg, the quantification limit was 2.0 mg/kg, and the spiked recoveries were in the range of 99.37-110.16%. The relative standard deviations (RSDs) were in the range of 0.17-1.26%. Four samples were tested and analyzed by the established method, and cyclohexylamine was not detected.


Asunto(s)
Ciclamatos , Cromatografía Líquida de Alta Presión/métodos , Ciclamatos/análisis , Ciclamatos/química , Calor , Ciclohexilaminas/química , Ciclohexilaminas/análisis
4.
Am J Med Sci ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39127419

RESUMEN

BACKGROUND: Given the previously reported harmful effects of abdominal fat burden on kidney function, we aim to investigate the relationship between major adverse kidney events within 30 days (MAKE30) and abdominal obesity in acute necrotizing pancreatitis (ANP) patients and explore the underlying risk factors. METHODS: A retrospective cohort study of all patients admitted within 72 h after the first episode of ANP to a tertiary center between June 2015 and June 2019 was conducted. Automatic image analysis software was used to calculate the area of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and skeletal muscle from computed tomography scans at the umbilical level. The potential risk factors of MAKE30 were analyzed by logistic regression. RESULTS: A total of 208 eligible ANP patients were enrolled, with an incidence of 23% for MAKE30. VAT area was more closely associated with the development of MAKE30, with an area under the ROC curve of 0.69 (cutoff value 200 cm2, 63.8% sensitivity and 66.7% specificity). Multivariate logistic regression analysis demonstrated that VAT area [OR 1.01 (1.01-1.02); p < 0.001] was an independent risk factor in predicting MAKE30. Patients with a VAT area > 200 cm2 had more requirements of renal replacement therapy (32% vs. 12%, P < 0.001), and a significantly higher incidence of other poor clinical outcomes (all p < 0.05). CONCLUSION: Early assessment of the VAT area may help identify ANP patients at high risk of MAKE30, suggesting that it could be a potential indicator for adverse kidney events.

5.
Bioresour Technol ; 409: 131259, 2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39137860

RESUMEN

The utilization of biomass pyrolysis is a crucial approach for sustainable development. This study used the typical biomass of pine (PI), rice husk (RH), and corn straw (ST) as feedstocks to evaluate the pyrolysis mechanisms, features and conversion mechanisms of the phenol tar product. The phenolic gaseous products were more trailing in ST, which mostly concentrated around 320-500 °C. Primary phenol tar is produced from lignin through the homolytic cleavage of ß-O and α-O, and C-C bond breakage, primarily occurring before 550 °C. As the degree of aromatization increases, the oxygenates progressively deoxygenate, and the primary tar demethoxylates to form secondary tar as the temperature increases. The pyrolysis of cellulose produces H radicals, which aid the transformation of lignin into phenol tar. This study can provide a theoretical basis for biomass pyrolysis to select the appropriate process parameters to improve the quality of bio-oil and regulate phenol tar products.

6.
ACS Appl Bio Mater ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39146214

RESUMEN

We establish an in vitro perfusion intestinal tissue bioreactor system tailored to study drug responses related to inflammatory bowel disease (IBD). The system includes key components including multiple human intestinal cell types (colonoids, myofibroblasts, and macrophages), a three-dimensional (3D) intestinal architecture, and fluid flow. Inclusion of myofibroblasts resulted in increased secretion of cytokines such as glypican-1 (GCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin 1-α (IL-1α), whereas inclusion of macrophages resulted in increased secretion of monocyte chemoattractant proteins (MCPs) demonstrating a significant role of both stromal and immune cell types in intestinal inflammation. The system is responsive to drug treatments, as reflected in the reduction of pro-inflammatory cytokine production in tissue in some treatment scenarios. While future studies are needed to evaluate more nuanced responses in an IBD context, the present study demonstrates the ability to establish a 3D intestinal model with multiple relevant cell types and flow that is responsive to both inflammatory cues and various drug treatment options.

7.
Rev Cardiovasc Med ; 25(7): 253, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39139432

RESUMEN

Background: To evaluate the effectiveness of the surgical approach in patients with congenital heart disease and pulmonary hypertension (PH). Methods: This was a retrospective clinical review of patients with congenital heart disease and PH who underwent pulmonary artery banding (PAB) at our institution between January 2013 and January 2023. Results: We identified 219 patients (53.4% males) with a median age of 7 (4.0-15.0) months and a median weight of 6.8 (5.2-9.0) kg at the time of PAB. The median hospital stay was 7.0 (5.0-10.0) days. The in-hospital mortality rate was 4.6%. The median follow-up was 33.0 (17.0-61.0) months. Survival rates were 96.9 ± 2.5% at 60 months and 92.1 ± 6.9% at 120 months post-PAB. 43.8% of patients had a de-banding procedure, and 147 (79.0%) patients received a second-stage procedure (34.7% univentricular, 65.3% biventricular). The mortality rate between stages was 4.3%. 21 (9.6%) patients reached a third-stage procedure. The overall mortality rate was 9.1%. Conclusions: PAB is an acceptable strategy for patients with congenital heart disease complicated with PH. The results and outcomes of subsequent univentricular or biventricular procedures are generally good.

8.
Environ Sci Technol ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39143808

RESUMEN

Fluorinated liquid-crystal monomers (FLCMs) are a potential emerging class of persistent, bioaccumulative, and toxic compounds. Humans inevitably ingest FLCMs via food and the environment. However, there are limited studies on internal exposure biomonitoring of FLCMs. Herein, we evaluated the estimated daily intakes (EDIs) of FLCMs in the general population based on serum residue levels. For the first time, 38 FLCMs were detected in 314 serum samples from the general population in Beijing, with a median value of 132.48 ng/g of lipid weight (lw). BDPrB is a predominant FLCM in serum. The median EDI of ∑38FLCMs in the general residents was 37.96 pg/kg bw/day. The residual levels of most FLCMs were higher in urban than in suburban areas (p < 0.05). The concentrations of EFPEB, EDPrB, EDFPBB, and PDTFMTFT in serum showed positive associations with blood glucose (GLU) (r = 0.126-0.275, p < 0.05). Logistic regression analysis showed that FLCMs were significantly positively correlated with dyslipidemia, with an odds ratio of 2.19; BDPrB was significantly positively correlated with hyperglycemia (OR: 2.48). Overall, the present study suggests the occurrence of FLCMs in the nonoccupational population, and the exposure of certain FLCMs may cause abnormal blood glucose and lipid levels.

9.
Sci Total Environ ; : 175543, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39153619

RESUMEN

Carbon(C), nitrogen(N), and phosphorus(P) are crucial elements in the element cycling in the terrestrial ecosystems. In the past decades, the spatial pattern and driving mechanism of plant and soil ecological stoichiometry have been hot topics in ecological geography. So far, many studies at different spatial and ecological scales have been conducted, but systematic review has not been reported to summarize the research status. In this paper, we tried to fill this gap by reviewing both the spatial variations and driving factors of C, N, P stoichiometric characteristics of plant and soil at regional to large scale. Additionally, we synthesized researches on the relationships between plant and soil C, N and P stoichiometric characteristics. At the global scale, plant C, N, P stoichiometric characteristics exhibited some trends along latitude and temperature gradient. Plant taxonomic classification was the main factor controlling the spatial variations of plant C, N and P stoichiometric characteristics. Climate factor and soil properties showed varying impacts on the spatial variations of plant C, N, P stoichiometric characteristics across different spatial scales. Soil C, N, P stoichiometric characteristics also vary along climate gradient at large scale. Their spatial variations result from the combined effects of climate, topography, soil properties, and vegetation characteristics at regional scale. The spatial pattern of soil C, N, P stoichiometric characteristics and the driving effects from environmental factors could be notably different among different ecosystems and vegetation types. Plant C:N:P is obviously higher than that of soil, and there exists a positive correlation between plant and soil C:N:P. Their trends along longitude and latitude are similar, but this correlation varies significantly among different vegetation types. Finally, based on the issues identified in this paper, we highlighted eight potential research themes for the future studies.

12.
Front Pediatr ; 12: 1394403, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39105162

RESUMEN

Objective: To investigate the surgical outcomes and complication rates of traditional circumcision and disposable circumcision stapler in the treatment of pediatric patients with phimosis and redundant prepuce. Methods: A retrospective analysis was conducted on pediatric patients with phimosis or preputial redundancy treated at our pediatric surgery department from January 2022 to December 2023. The patients were divided into two groups: treated with traditional circumcision (control group) and treated with a disposable circumcision stapler (experimental group). Surgical parameters (operation time, intraoperative bleeding), postoperative outcomes (postoperative pain scores, wound healing time, severe edge swelling, wound dehiscence, postoperative rebleeding, postoperative infection, aesthetic satisfaction), were compared between the two groups. Results: A total of 301 pediatric patients were included in our study, with 146 in the traditional group and 155 in the stapler group. The stapler group showed significantly lower values in operation time, intraoperative bleeding, and postoperative rebleeding compared to the traditional group (P < 0.05). However, the traditional group had a significant advantage in postoperative wound healing time and the occurrence of severe edge swelling (P < 0.05). There were no significant differences between the two groups in terms of anesthetic drug dosage, postoperative pain level, postoperative infection rate, wound dehiscence, and aesthetic satisfaction (P > 0.05). Conclusion: In the treatment of pediatric phimosis and redundant prepuce, the advantage of traditional circumcision lies in faster postoperative recovery and less severe edge swelling. The disposable circumcision stapler excels in thorough hemostasis, easy and safe operation, suitable for primary medical use, but lags behind in postoperative recovery compared to the traditional method. Each treatment approach has its own advantages, and the choice should be based on the actual condition and circumstances of the patient. Personalized treatment decisions should be made collaboratively to achieve the best therapeutic outcomes.

13.
Materials (Basel) ; 17(15)2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39124306

RESUMEN

Sand solidification of earth-rock dams is the key to flood discharge capacity and collapse prevention of earth-rock dams. It is urgent to find an economical, environmentally friendly, and durable sand solidification technology. However, the traditional grouting reinforcement method has some problems, such as high costs, complex operations, and environmental pollution. Enzyme-induced calcium carbonate precipitation (EICP) is an anti-seepage reinforcement technology emerging in recent years with the characteristics of economy, environmental protection, and durability. The erosion resistance and shear strength of earth-rock dams solidified by EICP need further verification. In this paper, EICP-solidified standard sand is taken as the research object, and EICP-cemented standard sand is carried out by a consolidated undrained triaxial test. A two-stage pouring method is adopted to pour samples, and the effects of dry density, cementation times, standing time, and confining pressure on the shear strength of cemented standard sand are emphatically analyzed. The relationship between cohesion, internal friction angle, and CaCO3 formation was analyzed. After the optimal curing conditions are obtained through the triaxial shear strength test, the erosion resistance model test is carried out. The effects of erosion angle, erosion flow rate, and erosion time on the erosion resistance of EICP-solidified sand were analyzed through an erosion model test. The results of triaxial tests show that the standard sand solidified by EICP exhibits strain softening, and the peak strength increases with the increase in initial dry density, cementation times, standing time, and confining pressure. When the content of CaCO3 increases from 2.84 g to 12.61 g, the cohesive force and internal friction angle change to 23.13 times and 1.18 times, and the determination coefficients reach 0.93 and 0.94, respectively. Erosion model test results indicate that the EICP-solidified sand dam has good erosion resistance. As the increase in erosion angle, erosion flow rate, and erosion time, the breach of solidified samples gradually becomes larger. Due to the deep solidification of sand by EICP, the development of breaches is relatively slow. Under different erosion conditions, the solidified samples did not collapse and the dam broke. The research results have important reference value and scientific significance for the practice of sand consolidation engineering in earth-rock dams.

14.
Org Lett ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39140838

RESUMEN

(Hetero)arylated bicyclo[1.1.1]pentanes (BCPs) are important for the construction of complex druglike target molecules. Herein, we developed a method for light-induced, Cs2CO3-promoted homolytic cleavage of pyridinium C-N bonds for generating alkyl radicals from amino acid-derived Katritzky salts and use of the radicals for functionalization of [1.1.1]propellane to rapidly generate (hetero)arylated BCPs. The method features excellent functional group tolerance and a broad substrate scope and can be used to functionalize structurally complex natural products.

15.
ACS Omega ; 9(30): 33044-33054, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39100341

RESUMEN

Due to the fact that more conventional heavy oil recovery methods (heating, emulsification, dilution, and other methods) have many shortcomings, they cannot meet the demand of heavy oil exploitation. Therefore, there is a need for new recovery methods. In this paper, the surface of nano SiO2 was modified with a silane coupling agent, KH-560, to prepare a nanoviscosity reducer (NRV), which has high-temperature resistance (300 °C), calcium and magnesium resistance (Ca2+ + Mg2+ > 900 mg/L) and high viscosity reduction rate (>99%). FTIR and SEM measurements showed that KH560 has been successfully connected to the surface of SiO2. The particle size distribution of NRV is mainly distributed in 50-80 nm, which matches the results of SEM. The experimental results showed that the viscosity reduction rates of 1 wt % NRV on M-1 heavy oil before and after aging were 99.73% and 99.71%, respectively. The viscosity reduction effect of 1% NRV on M-1 heavy oil and the bleeding rate of emulsion formation were investigated when the oil-water ratio ranged from 9:1 to 1:9. The results showed that when the oil-water ratio was between 7:3 and 1:9, the viscosity reduction rate was greater than 99%. Besides, the bleeding rate of emulsion increases with the decrease of the oil-water ratio. What's more, static and dynamic adsorption experiments showed that the adsorption capacity of 1 wt % NRV was 1.746 mg/g and 1.668 mg/g sand, respectively. The interfacial tension experiment showed that the interfacial tension (IFT) between 1 wt % NRV and M-1 heavy oil was 0.052 mN/m, and low interfacial tension was beneficial to displace the oil in the formation pores. At the same time, the displacement effect of NRV on M-1 heavy oil at different concentrations (0.5, 1.0, and 1.5 wt %) and temperatures (200, 250, and 300 °C) was investigated by core flooding experiments. The results showed that the recovery rate increases with the increase of NRV concentration, and 1 wt % NRV at 300 °C will improve the recovery rate of M-1 heavy oil by 27.3% compared to steam flooding. NRV could reduce the viscosity of crude oil, which provides technical guidelines for the exploitation of heavy oil and extra heavy oil.

16.
Front Public Health ; 12: 1398396, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39100956

RESUMEN

Accumulating research suggested that long-term exposure to fine particulate matter (PM2.5) is related to cardiovascular disease (CVD). However, evidence regarding the relationship between PM2.5 and CVD risk factors remains inconsistent. We hypothesized that this association may be partially modified by socioeconomic status (SES). To investigate the relationships and to test the modifying effect of SES, we included baseline data for 21,018 adults from September 2017 to May 2018. PM2.5 concentrations were determined by employing an amalgamation of linear measurements obtained from monitoring stations located near the participants' residential and workplace addresses. We assessed SES across several domains, including income, education, and occupation levels, as well as through a composite SES index. The results indicated that for every 10 µg/m3 increase in PM2.5 exposure, the risk of hypercholesterolemia, hyperbetalipoproteinemia, diabetes, and hyperhomocysteinemia (HHcy) increased by 7.7% [Odds ratio (OR) = 1.077, 95% Confidence Interval (CI) = 1.011, 1.146], 19.6% (OR = 1.196, 95% CI = 1.091, 1.312), 4.2% (OR = 1.042, 95% CI = 1.002, 1.084), and 17.1% (OR = 1.171, 95% CI = 1.133, 1.209), respectively. Compared to the high SES group, those with low SES are more prone to hypercholesterolemia, hyperbetalipoproteinemia, diabetes, and HHcy. Notably, the disparities in SES appear significant in the relationship between PM2.5 exposure and hypercholesterolemia as well as hyperbetalipoproteinemia. But for diabetes and HHcy, the modification effect of SES on PM2.5 shows an inconsistent pattern. In conclusion, the results confirm the association between PM2.5 and cardiovascular risk factors and low SES significantly amplified the adverse PM2.5 effect on dyslipidemia. It is crucial to emphasize a need to improve the socioeconomic inequality among adults in Beijing and contribute to the understanding of the urgency in protecting the health of vulnerable groups.


Asunto(s)
Enfermedades Cardiovasculares , Exposición a Riesgos Ambientales , Factores de Riesgo de Enfermedad Cardiaca , Material Particulado , Clase Social , Humanos , Material Particulado/análisis , Masculino , Femenino , Estudios Transversales , Beijing/epidemiología , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Adulto , Anciano , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/efectos adversos , Factores de Riesgo , Contaminación del Aire/efectos adversos
17.
Neural Regen Res ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39101644

RESUMEN

Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response, with resident microglia and infiltrating macrophages playing pivotal roles. While previous studies have grouped these two cell types together based on similarities in structure and function, an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes. In this study, we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury. Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury, gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed. Regarding macrophages, our findings highlighted abundant communication with other cells, including fibroblasts and neurons. Both pro-inflammatory and neuroprotective effects of macrophages were also identified; the pro-inflammatory effect may be related to integrin ß2 (Itgb2) and the neuroprotective effect may be related to the oncostatin M pathway. These findings were validated by in vivo experiments. This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury, and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.

18.
Acta Pharmacol Sin ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39112771

RESUMEN

Esculetin (ESC) is a coumarin-derived phytochemical prevalent in traditional Chinese medicine that exhibits anti-acute ischemic stroke activities. Our previous studies demonstrate that CKLF1 is a potential anti-stroke target for coumarin-derived compound. In this study we investigated whether CKLF1 was involved in the neuroprotective effects of ESC against photothrombotic stroke in mice. The mice were treated with ESC (20, 40 or 80 mg·kg-1·d-1, i.g.) for two weeks. The therapeutic effect of ESC was assessed using MRI, neurological function evaluation, and a range of behavioral tests on D1, 3, 7 and 14 of ESC administration. We showed that oral administration of ESC dose-dependently reduced the cerebral infarction volume within one week after stroke, improved behavioral performance, and alleviated neuropathological damage within two weeks. Functional MRI revealed that ESC significantly enhanced the abnormal low-frequency fluctuation (ALFF) value of the motor cortex and promoted functional connectivity between the supplementary motor area (SMA) and multiple brain regions. We demonstrated that ESC significantly reduced the protein levels of CKLF1 and CCR5, as well as the CKLF1/CCR5 protein complex in the peri-infarcted area. We showed that ESC (0.1-10 µM) dose-dependently blocked CKLF1-induced chemotactic movement of neutrophils in the Transwell assay, reducing the interaction of CKLF1/CCR5 on the surface of neutrophils, thereby reducing neutrophil infiltration, and decreasing the expression of ICAM-1, VCAM-1 and MMP-9 in the peri-infarct tissue. Knockout of CKLF1 reduced brain infarction volume and motor dysfunction after stroke but also negated the anti-stroke efficacy and neutrophil infiltration of ESC. These results suggest that the efficacy of ESC in promoting post-stroke neural repair depends on its inhibition on CKLF1-mediated neutrophil infiltration, which offering novel perspectives for elucidating the therapeutic properties of coumarins.

19.
Bone Res ; 12(1): 42, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103328

RESUMEN

Ageing as a natural irreversible process inherently results in the functional deterioration of numerous organ systems and tissues, including the skeletal and immune systems. Recent studies have elucidated the intricate bidirectional interactions between these two systems. In this review, we provide a comprehensive synthesis of molecular mechanisms of cell ageing. We further discuss how age-related skeletal changes influence the immune system and the consequent impact of immune system alterations on the skeletal system. Finally, we highlight the clinical implications of these findings and propose potential strategies to promote healthy ageing and reduce pathologic deterioration of both the skeletal and immune systems.


Asunto(s)
Envejecimiento , Huesos , Sistema Inmunológico , Humanos , Envejecimiento/inmunología , Envejecimiento/fisiología , Sistema Inmunológico/inmunología , Sistema Inmunológico/fisiología , Huesos/inmunología , Animales
20.
Sci Rep ; 14(1): 19246, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164309

RESUMEN

Among the many adverse geological disasters, the surge water disaster in karst areas causes the greatest loss to underground engineering construction, so it is necessary to carry out relevant research on the management of surge water disaster in karst pipelines. This study presents the creation of an oily epoxy resin magnetic convergence grouting material (OEMS) specifically developed to prevent water infiltration in pipelines. A self-designed visual karst pipeline grouting simulation system was used to conduct an experimental study on the diffusion and plugging behavior of magnetic slurry grouting. A model was constructed to simulate the migration of a magnetic slurry in water inrush circumstances. The model is based on the theory of slurry diffusion and the concept of magnetic adsorption. The results suggest that:(i) The best performance in grouting sealing is achieved when the ratio of new OEMS epoxy resin A liquid to B liquid is 2:1, and the blending ratio of flyash and Fe3O4 powder falls between 25 and 55%. (ii) The primary and secondary correlations among the parameters that affect the rate of change in flow rate, plugging pressure, and slurry retention rate are as follows: Hydrodynamic velocity has the greatest correlation, followed by plugging length, Fe3O4 power ratio, and flyash mixture ratio. (iii) The validity of the model is verified by comparing empirical observations with calculated theoretical values.

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