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1.
Development ; 151(11)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38770916

ABSTRACT

Prolyl hydroxylase domain (PHD) proteins are oxygen sensors that use intracellular oxygen as a substrate to hydroxylate hypoxia-inducible factor (HIF) α proteins, routing them for polyubiquitylation and proteasomal degradation. Typically, HIFα accumulation in hypoxic or PHD-deficient tissues leads to upregulated angiogenesis. Here, we report unexpected retinal phenotypes associated with endothelial cell (EC)-specific gene targeting of Phd2 (Egln1) and Hif2alpha (Epas1). EC-specific Phd2 disruption suppressed retinal angiogenesis, despite HIFα accumulation and VEGFA upregulation. Suppressed retinal angiogenesis was observed both in development and in the oxygen-induced retinopathy (OIR) model. On the other hand, EC-specific deletion of Hif1alpha (Hif1a), Hif2alpha, or both did not affect retinal vascular morphogenesis. Strikingly, retinal angiogenesis appeared normal in mice double-deficient for endothelial PHD2 and HIF2α. In PHD2-deficient retinal vasculature, delta-like 4 (DLL4, a NOTCH ligand) and HEY2 (a NOTCH target) were upregulated by HIF2α-dependent mechanisms. Inhibition of NOTCH signaling by a chemical inhibitor or DLL4 antibody partially rescued retinal angiogenesis. Taken together, our data demonstrate that HIF2α accumulation in retinal ECs inhibits rather than stimulates retinal angiogenesis, in part by upregulating DLL4 expression and NOTCH signaling.


Subject(s)
Animals, Newborn , Basic Helix-Loop-Helix Transcription Factors , Endothelial Cells , Hypoxia-Inducible Factor-Proline Dioxygenases , Receptors, Notch , Retinal Neovascularization , Signal Transduction , Up-Regulation , Animals , Basic Helix-Loop-Helix Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Mice , Receptors, Notch/metabolism , Receptors, Notch/genetics , Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism , Hypoxia-Inducible Factor-Proline Dioxygenases/genetics , Retinal Neovascularization/metabolism , Retinal Neovascularization/genetics , Retinal Neovascularization/pathology , Endothelial Cells/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Retina/metabolism , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Calcium-Binding Proteins/metabolism , Calcium-Binding Proteins/genetics , Retinal Vessels/metabolism , Angiogenesis
2.
Anal Chim Acta ; 1307: 342620, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38719413

ABSTRACT

BACKGROUND: Pharmacokinetic studies are pivotal in drug development, focusing on absorption, distribution, and excretion of active compounds. Effective sample preparation methods play a crucial role in these studies. Traditional techniques like protein precipitation and liquid-liquid extraction often involve toxic solvents and are time-consuming. Recently, deep eutectic solvent (DES) has emerged as an eco-friendly alternative due to its high efficiency, low cost, and low toxicity. This study introduces a novel sample pretreatment method using CO2-switchable DES in liquid-liquid microextraction (LLME) to enhance speed, accuracy, and sensitivity in complex biological samples analysis. RESULTS: A liquid-liquid microextraction sample pretreatment method based on switchable DES combined with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established for the analysis of urine and tissue samples. The method was optimized through systematic investigation of key parameters, including DES type, volume, molar ratio, pH, vortex time, gas purge time, and salt addition. The resulting procedure exhibited satisfying linearity (r2 ≥ 0.9958), good precision (RSD ≤6.01 %), desirable recovery (52.44%-98.12 %) and matrix effect (86.22%-119.30 %), and the accuracy and precision of stability were within the ±15 % limit. The proven methods were further applied to urinary excretion study and tissue distribution study of Nelumbinis plumula (NP) extract. The results indicated that the total cumulative excretion of liensinine, isoliensinine and neferine in urine within 240 h was 4.96 %, 0.66 % and 0.44 %, respectively. The tissue distribution study showed that alkaloids mainly distribute in liver, kidney, and spleen. SIGNIFICANCE: This research introduces a groundbreaking technique distinguished by its simplicity, speed, cost-effectiveness, and environmental friendliness. This approach, utilizing CO2-switchable DES as an extraction solvent for LLME, integrates deproteinization and removal of interfering molecules into a single step. This integration showcases its efficiency and convenience, demonstrating significant promise for various applications in the analysis of biological samples. Additionally, this study provides the first report on urinary excretion and tissue distribution of alkaloids from NP using a DES-LLME method. These findings offer valuable insights into the in vivo behavior of herbal medicine, enhancing understanding of pharmacological actions and facilitating clinical rational administration.


Subject(s)
Carbon Dioxide , Deep Eutectic Solvents , Liquid Phase Microextraction , Tandem Mass Spectrometry , Liquid Phase Microextraction/methods , Carbon Dioxide/chemistry , Deep Eutectic Solvents/chemistry , Animals , Tissue Distribution , Tandem Mass Spectrometry/methods , Chromatography, High Pressure Liquid , Male , Rats , Rats, Sprague-Dawley
3.
J Hazard Mater ; 474: 134728, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38805824

ABSTRACT

Microplastics are accumulating rapidly in aquatic ecosystems, providing habitats for pathogens and vectors for antibiotic resistance genes (ARGs), potentially increasing pathogenic risks. However, few studies have considered microplastics as particulate organic matter (POM) to elucidate their pathogenic risks and underlying mechanisms. Here, we performed microcosm experiments with microplastics and natural POM (leaves, algae, soil), thoroughly investigating their distinct effects on the community compositions, functional profiles, opportunistic pathogens, and ARGs in Particle-Associated (PA) and Free-Living (FL) bacterial communities. We found that both microplastics and leaves have comparable impacts on microbial community structures and functions, enriching opportunistic pathogens and ARGs, which may pose potential environmental risks. These effects are likely driven by their influences on water properties, including dissolved organic carbon, nitrate, DO, and pH. However, microplastics uniquely promoted pathogens as keystone species and further amplified their capacity as hosts for ARGs, potentially posing a higher pathogenic risk than natural POM. Our research also emphasized the importance of considering both PA and FL bacteria when assessing microplastic impacts, as they exhibited different responses. Overall, our study elucidates the role and underlying mechanism of microplastics as an emerging POM in intensifying pathogenic risks of aquatic ecosystems in comparison with conventional natural POM.

4.
Materials (Basel) ; 17(10)2024 May 18.
Article in English | MEDLINE | ID: mdl-38793499

ABSTRACT

In this study, alumina ceramics with hierarchical pores were successfully fabricated using freeze casting. Experimental studies show that both the solid loading of the slurry and the thermal insulation layer at the interface of the slurry and cooling plate can influence the pore characteristics of cast samples. In order to examine the pore characteristics and evaluate the permeability of the freeze-cast samples fabricated under different conditions, a generative adversarial network (GAN) method was employed to reconstruct the three-dimensional (3D) microstructure from two-dimensional (2D) scanning electron microscopy (SEM) images of the samples. Furthermore, GAN 3D reconstruction was validated against X-ray tomography 3D reconstruction results. Based on the GAN reconstructed microstructures, the permeability and pore distribution of the various samples were analyzed. The sample cast with 35 wt.% solid loading shows an optimal permeability.

5.
J Cardiothorac Surg ; 19(1): 227, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627839

ABSTRACT

OBJECTIVE: To investigate the clinical significance of the creatine kinase (CK)-MB/total CK ratio, neutrophil/lymphocyte ratio (NLR) and red blood cell distribution width in acute myocardial infarction (AMI). METHODS: A retrospective analysis was conducted of 196 AMI cases from our hospital's cardiology department; healthy people were selected over the same period as the control. The two groups' test indexes were compared through multivariate logistic regression analysis to screen for AMI risk factors; the receiver operating characteristic (ROC) curve was used to evaluate their AMI predictive values. RESULTS: The serum CK, CK-MB, CK index, neutrophils and NLR values in the AMI group were significantly higher compared with those in the control group (p < 0.05); however, the levels of serum lymphocytes were significantly lower compared with those in the control group (p < 0.05). Multivariate logistic regression analysis showed that elevated CK-MB and NLR levels were risk factors for AMI (p < 0.05). The ROC curve showed that the area under the curve of the NLR and CK levels were 0.917 and 0.594, respectively. CONCLUSION: The CK index and NLR have a clinical predicting value for AMI and could be used as a clinical auxiliary diagnostic index for the assessment of patients with AMI.


Subject(s)
Myocardial Infarction , Neutrophils , Humans , Creatine Kinase , Retrospective Studies , Sensitivity and Specificity , Biomarkers , Creatine Kinase, MB Form , Myocardial Infarction/diagnosis , ROC Curve , Lymphocytes
6.
Ecotoxicol Environ Saf ; 277: 116380, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38677068

ABSTRACT

The interaction between microplastics (MPs) and cadmium (Cd) poses a threat to agricultural soil environments, and their effects on plant growth and rhizosphere microbial community functions are not yet clear. In this study, energy sorghum was used as a test plant to investigate the effects of two types of MPs, polystyrene (PS) and polyethylene (PE), at different particle sizes (13 µm, 550 µm) and concentrations (0.1%, 1% w/w), and Cd, as well as their interactions, on the growth of sorghum in a soil-cultivation pot experiment. The results showed that the combined effects of MP and Cd pollution on the dry weight and Cd accumulation rate in sorghum varied depending on the type, concentration, and particle size of the MPs, with an overall trend of increasing stress from combined pollution with increasing Cd content and accumulation. High-throughput sequencing analysis revealed that combined MP and Cd pollution increased bacterial diversity, and the most significant increase was observed in the abundance-based coverage estimator (ACE), Shannon, and Sobs indices in the 13 µm 1% PS+Cd treatment group. Metagenomic analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways revealed that 19 groups of metabolic pathways, including microbial metabolism and methane metabolism, differed significantly under combined MP and Cd pollution. Hierarchical clustering results indicated that Cd treatment and combined MP and Cd treatment affected the abundances of sorghum rhizosphere soil nitrogen (N) and phosphorus (P) cycling genes and that the type of MP present was an important factor affecting N and P cycling genes. The results of this study provide a basis for exploring the toxic effects of combined MP and Cd pollution and for conducting soil environmental risk assessments.


Subject(s)
Cadmium , Microplastics , Rhizosphere , Soil Microbiology , Soil Pollutants , Sorghum , Sorghum/drug effects , Sorghum/microbiology , Cadmium/toxicity , Soil Pollutants/toxicity , Microplastics/toxicity , Soil/chemistry , Particle Size , Bacteria/drug effects
7.
ACS Omega ; 9(14): 16486-16495, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38617698

ABSTRACT

Spraying harvesting aids is an important step before the mechanical harvesting of cotton. To clarify the direct relationship between the droplet density and the defoliation effect of cotton harvest aid solutions, we evaluated the relationship between the droplet density and the defoliation effect. The determination method and evaluation standard of the number of droplets required per square centimeter to achieve 50% leaves defoliation (DN50) of the harvest aid solution were further explored. The results revealed a linear relationship between the droplet density and the cotton defoliation rate when the spraying volume was 22.5 L/ha and the harvest aid dosage was 1/2 and 2/3 of the recommended dosage. When the harvest aid dosage was 5/6 and 1 times the recommended dosage, the relationship between the droplet density and the defoliation rate of cotton was logarithmic. The DN50 of the low-concentration harvest aid solution (450 L/ha) was significantly higher than that of the high-concentration solution (22.5 L/ha). The addition of spray adjuvant Beidatong significantly reduced the DN50 of cotton harvest aids. The field experiment showed that the droplet density increased with the increase of the spraying volume sprayed by unmanned aerial vehicles. There was a positive correlation between the spraying volume and the defoliation effect after changes in the cotton harvest aid dosage. When the dosage of Mianhai (MH) was 5/6 of the recommended dosage, the defoliation effect at the spraying volumes of 22.5, 27.0, and 30.0 L/ha reached the peak values at 71.54, 78.56, and 83.23%, respectively. This study proposed the concept of DN50 and its determination method. The fitting equations between the droplet density and defoliation effect and between the harvest aid concentration and defoliation effect were established to provide a theoretical basis for the scientific spraying of cotton harvest aid solutions.

9.
Heliyon ; 10(7): e28826, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38596127

ABSTRACT

Oral microecological dysregulation has been shown to be associated with various immune system disorders. Henoch-schonlein purpura (HSP) is an autoimmune small vessel inflammatory disease in children of uncertain etiology, and studies have suggested that streptococcal infection may be an influential factor in its development. However, the relationship between oral microecological dysregulation and HSP has not been clearly studied so far. In this study, an epidemiological survey on the oral health status of children with HSP was investigated in this paper, and collected dental plaque from four groups of children for 16SrDNA high-throughput sequencing to analyze the composition and changes of oral microbial diversity among different groups. The results showed that the oral health status of children with HSP was poor, except for the incidence of caries in the 5-year-old group, the caries rate and dmfs/DMFS in the 3,4 and 5-year-old groups were higher than the same age in the fourth Chinese Oral Health Epidemiological Survey. Moreover, the development of HSP is accompanied by disturbances in the oral microbiota; a decrease in the number of Firmicutes which producing butyric acid may be closely associated with the development of HSP; changes in the abundance of Streptococcus and Neisseria may be a risk factor for the development of HSP.

10.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1353-1360, 2024 Mar.
Article in Chinese | MEDLINE | ID: mdl-38621983

ABSTRACT

This study aims to investigate the effect of Xixin Decoction on the T helper 17 cell(Th17)/regulatory T cell(Treg) ba-lance of intestinal mucosa and the expression of related transcription factors in the senescence-accelerated mouse-prone 8(SAMP8) model. Fifty 14-week male mice of SAMP8 were randomized by the random number table method into model group, probiotics group, and high-, medium-, and low-dose Xixin Decoction groups, with 10 mice in each group. Ten 14-week male mice of senescence-acce-lerated mouse-resistant 1(SAMR1) served as control group. After 10 weeks of feeding, the mice were administrated with correspon-ding drugs for 10 weeks. Morris water maze test was carried out to examine the learning and memory abilities of mice. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the content of secretory immunoglobulin A(SIgA) in the intestinal mucosa, and flow cytometry to detect the percentage content of Th17 and Treg in the intestinal mucosa. Western blot was performed to determine the protein levels of retinoid-related orphan receptor gamma t(RORγt) and forkhead box p3(Foxp3) in the mouse colon tissue. Compared with control group, the escape latency of mice in model group was significantly prolonged(P<0.01), and the number of times of crossing the platform and the residence time in the target quadrant were significantly reduced within 60 s(P<0.01), intestinal mucosal SIgA content was significantly decreased(P<0.01), Th17 content was increased(P<0.05), Treg content was decreased(P<0.01), the expression of RORγt protein was increased and Foxp3 protein was decreased in colon(P<0.01). Compared with the model group, high-dose Xixin Decoction group improved the learning and memory ability(P<0.05 or P<0.01). Probiotics group and high-and medium-dose Xixin Decoction group increased the content of SIgA in intestinal mucosa(P<0.05 or P<0.01), decreased percentage content of Th17 and increased the percentage content of Treg in intestinal mucosa(P<0.05 or P<0.01). Furthermore, they down-regulated the protein level of RORγt and up-regulated the protein level of Foxp3 in the intestinal mucosa(P<0.01). In conclusion, Xixin Decoction may act on intestinal mucosal immune barrier, affect gut-brain information exchange, and improve the learning and memory ability of SAMP8 by promoting SIgA secretion and regulating the Th17/Treg balance and the expression of RORγt and Foxp3.


Subject(s)
T-Lymphocytes, Regulatory , Th17 Cells , Mice , Male , Animals , Nuclear Receptor Subfamily 1, Group F, Member 3/genetics , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Immunoglobulin A, Secretory/pharmacology
11.
J Phys Condens Matter ; 36(25)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38478994

ABSTRACT

The geometric structure of the BAs/WTe2heterojunction was scrutinized by employingab initiocalculations grounded on density functional theory. Multiple configurations are constructed to determine the equilibrium state of the heterojunction with optimal stability. The results show that the H1-type heterojunction with interlayer distance of 3.92 Å exhibits exceptional stability and showcases a conventional Type-II band alignment, accompanied by a direct band gap measuring 0.33 eV. By applying external electric field and introducing strain, one can efficaciously modulate both the band gap and the quantity of charge transfer in the heterojunction, accompanied by the transition of band alignment from Type-II to Type-I, which makes it expected to achieve broader applications in light-emitting diodes, laser detectors and other fields. Ultimately, the heterojunction undergoes a transformation from a semiconducting to a metallic state. Furthermore, the outstanding optical characteristics inherent to each of the two monolayers are preserved, the BAs/WTe2heterojunction also serves to enhance the absorption coefficient and spectral range of the material, particularly within the ultraviolet spectrum. It merits emphasis that the optical properties of the BAs/WTe2heterojunction are capable of modification through the imposition of external electric fields and mechanical strains, which will expand its applicability and potential for future progression within the domains of nanodevices and optoelectronic apparatus.

12.
Bioeng Transl Med ; 9(2): e10623, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38435823

ABSTRACT

The biological barriers of the body, such as the blood-brain, placental, intestinal, skin, and air-blood, protect against invading viruses and bacteria while providing necessary physical support. However, these barriers also hinder the delivery of drugs to target tissues, reducing their therapeutic efficacy. Extracellular vesicles (EVs), nanostructures with a diameter ranging from 30 nm to 10 µm secreted by cells, offer a potential solution to this challenge. These natural vesicles can effectively pass through various biological barriers, facilitating intercellular communication. As a result, artificially engineered EVs that mimic or are superior to the natural ones have emerged as a promising drug delivery vehicle, capable of delivering drugs to almost any body part to treat various diseases. This review first provides an overview of the formation and cross-species uptake of natural EVs from different organisms, including animals, plants, and bacteria. Later, it explores the current clinical applications, perspectives, and challenges associated with using engineered EVs as a drug delivery platform. Finally, it aims to inspire further research to help bioengineered EVs effectively cross biological barriers to treat diseases.

13.
J Environ Manage ; 355: 120226, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38430876

ABSTRACT

This study aims to evaluate the feasibility and safety of using municipal solid waste incineration fly ash (MSW-IFA) in the development of geopolymer-based solidification/stabilization (S/S) treatments. Geopolymers have garnered attention as a sustainable alternative to traditional cement, owing to their high strength, stability, and minimal CO2 emissions. In this study, a combination of experimental and simulation calculations was used to investigate the setting time, mechanical properties, environmental risks, hydration mechanisms and processes of municipal solid waste incineration fly ash-based polymeric functional cementitious materials (GFCM). The results demonstrate that the mechanical properties of GFCM are related to the changes in the mineral phases and the degree of compactness. Quantum chemical calculations indicate that the hydration products may be [Si(OH)4], [Al(OH)3(OH2)] and [Al(OH)4]-. It is possible that the heavy metals are embedded in the hydrated silica-aluminate by electrostatic interaction or chemisorption. Heavy metals may be embedded in hydrated silica-aluminate by electrostatic action or chemisorption. This study provides a feasible method for resource utilization and heavy metal stabilization mechanism of MSW-IFA.


Subject(s)
Metals, Heavy , Refuse Disposal , Coal Ash , Solid Waste/analysis , Particulate Matter , Carbon/chemistry , Incineration , Metals, Heavy/analysis , Silicon Dioxide , Refuse Disposal/methods
14.
ACS Omega ; 9(6): 6492-6504, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38371813

ABSTRACT

Extracellular vesicles (EVs) are increasingly used for disease diagnosis and treatment. Among them, red blood cell-derived EVs (RBC-EVs) have attracted great attention due to their abundant sources and low risks of gene transfer (RBC-EVs lack nuclear and mitochondrial DNA). Here, we first revealed the high expression level of membrane protein solute carrier family 4 member 1 (SLC4A1) in RBC-EVs through proteomic analysis. We then identified several binding peptides with high affinity for the SLC4A1 extracellular domain (SLC4A1-EC) from phage display library screening. A high affinity of SLC4A1-EC and the three peptides (XRB2, XRE4, and XRH7) were assessed in vitro using surface plasmon resonance analysis and SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The binding sites of SLC4A1-EC and polypeptides were further predicted by LigPlot + analysis, and the results showed that these three polypeptides could bind to part of the hydrophobic residues of SLC4A1-EC. The binding efficiency of the anchor peptides to the RBC-EVs was further verified by flow cytometry and fluorescence imaging. In conclusion, we successfully screened three specific RBC-EV-targeting peptides which could potentially be utilized for isolating RBC-derived EVs from serum samples. More importantly, this peptide could be coupled with targeting peptides to modify RBC-EVs for drug delivery. Our work will provide a viable method for optimizing the function of RBC-EVs.

16.
Circ Res ; 134(2): 165-185, 2024 01 19.
Article in English | MEDLINE | ID: mdl-38166463

ABSTRACT

BACKGROUND: Atherosclerosis is a globally prevalent chronic inflammatory disease with high morbidity and mortality. The development of atherosclerotic lesions is determined by macrophages. This study aimed to investigate the specific role of myeloid-derived CD147 (cluster of differentiation 147) in atherosclerosis and its translational significance. METHODS AND RESULTS: We generated mice with a myeloid-specific knockout of CD147 and mice with restricted CD147 overexpression, both in an apoE-deficient (ApoE-/-) background. Here, the myeloid-specific deletion of CD147 ameliorated atherosclerosis and inflammation. Consistent with our in vivo data, macrophages isolated from myeloid-specific CD147 knockout mice exhibited a phenotype shift from proinflammatory to anti-inflammatory macrophage polarization in response to lipopolysaccharide/IFN (interferon)-γ. These macrophages demonstrated a weakened proinflammatory macrophage phenotype, characterized by reduced production of NO and reactive nitrogen species derived from iNOS (inducible NO synthase). Mechanistically, the TRAF6 (tumor necrosis factor receptor-associated factor 6)-IKK (inhibitor of κB kinase)-IRF5 (IFN regulatory factor 5) signaling pathway was essential for the effect of CD147 on proinflammatory responses. Consistent with the reduced size of the necrotic core, myeloid-specific CD147 deficiency diminished the susceptibility of iNOS-mediated late apoptosis, accompanied by enhanced efferocytotic capacity mediated by increased secretion of GAS6 (growth arrest-specific 6) in proinflammatory macrophages. These findings were consistent in a mouse model with myeloid-restricted overexpression of CD147. Furthermore, we developed a new atherosclerosis model in ApoE-/- mice with humanized CD147 transgenic expression and demonstrated that the administration of an anti-human CD147 antibody effectively suppressed atherosclerosis by targeting inflammation and efferocytosis. CONCLUSIONS: Myeloid CD147 plays a crucial role in the growth of plaques by promoting inflammation in a TRAF6-IKK-IRF5-dependent manner and inhibiting efferocytosis by suppressing GAS6 during proinflammatory conditions. Consequently, the use of anti-human CD147 antibodies presents a complementary therapeutic approach to the existing lipid-lowering strategies for treating atherosclerotic diseases.


Subject(s)
Atherosclerosis , Plaque, Atherosclerotic , Mice , Animals , Efferocytosis , TNF Receptor-Associated Factor 6/metabolism , Atherosclerosis/metabolism , Inflammation/genetics , Mice, Knockout , Phenotype , Apolipoproteins E , Interferon Regulatory Factors/genetics , Mice, Inbred C57BL
17.
Psychiatry Clin Neurosci ; 78(2): 83-96, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37877617

ABSTRACT

Extracellular vesicles (EVs) are membrane-enclosed nanovesicles secreted by cells into the extracellular space and contain functional biomolecules, e.g. signaling receptors, bioactive lipids, nucleic acids, and proteins, which can serve as biomarkers. Neurons and glial cells secrete EVs, contributing to various physiological and pathological aspects of brain diseases. EVs confer their role in the bidirectional crosstalk between the central nervous system (CNS) and the periphery owing to their distinctive ability to cross the unique blood-brain barrier (BBB). Thus, EVs in the blood, cerebrospinal fluid (CSF), and urine can be intriguing biomarkers, enabling the minimally invasive diagnosis of CNS diseases. Although there has been an enormous interest in evaluating EVs as promising biomarkers, the lack of ultra-sensitive approaches for isolating and detecting brain-derived EVs (BDEVs) has hindered the development of efficient biomarkers. This review presents the recent salient findings of exosomal biomarkers, focusing on brain disorders. We summarize highly sensitive sensors for EV detection and state-of-the-art methods for single EV detection. Finally, the prospect of developing advanced EV analysis approaches for the non-invasive diagnosis of brain diseases is presented.


Subject(s)
Brain Diseases , Central Nervous System Diseases , Extracellular Vesicles , Humans , Brain/metabolism , Extracellular Vesicles/metabolism , Central Nervous System Diseases/diagnosis , Central Nervous System Diseases/metabolism , Brain Diseases/diagnosis , Biomarkers
18.
Chinese Pharmacological Bulletin ; (12): 299-307, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013590

ABSTRACT

Aim To explore the new mechanism of triptolide (TRI) inhibiting the progression of hepatocellular carcinoma (HCC) . Methods Different concentrations (0, 0 . 5, 2, and 8 jjunol • L~) of TRI were administered to act on liver cancer cells, and then the cell phenotypes and possible mechanisms were explored using experimental methods such as CCK-8, cell cloning, Transwell, and protein immunoblotting; siRNA was used to interfere with the target gene GSDME and its role was determined. Finally, the mechanism of TRI inhibiting the growth of HCC cells in vivo was validated using a transplanted tumor model. Results TRI could inhibit the proliferation, cloning, and invasion of HCC cells, and promote cell apoptosis. Immunoblotting results showed that the expression of GSDME was significantly upregulated in HepG2 or He-pal-6 hepatocellular carcinoma after TRI treatment, while the expression of cleaved caspase-3 and PARP also significantly increased. Knocking out GSDME could partially reverse TRI-induced cell apoptosis. At the same time, cells knocked down by GSDME had stronger cloning and migration abilities, and the apoptosis rate was reduced compared to the TRI treatment group alone. In vivo experiments showed that TRI inhibited HCC tumor growth, and the TRI + siGSDME group had a faster tumor growth rate than the TRI treatment group alone did. In addition, after TRI stimulation, p-eIF2a and ATF4 in HepG2 and Hepal-6 cells significantly increased. The immunofluorescence results showed a dose-dependent increase in the number of ATF4 positive cells in HepG2 and Hepal-6 cells after TRI stimulation. Conclusion The inhibitory effect of TRI on the growth and invasion of liver cancer cells may be related to its regulation of the ATF4/caspase-3/GSDME signaling pathway and promotion of liver cancer cell apoptosis.

19.
Neural Regen Res ; 19(5): 1126-1133, 2024 May.
Article in English | MEDLINE | ID: mdl-37862218

ABSTRACT

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death. China has the largest population of patients with traumatic spinal cord injury. Previous studies of traumatic spinal cord injury in China have mostly been regional in scope; national-level studies have been rare. To the best of our knowledge, no national-level study of treatment status and economic burden has been performed. This retrospective study aimed to examine the epidemiological and clinical features, treatment status, and economic burden of traumatic spinal cord injury in China at the national level. We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China. Patient epidemiological and clinical features, treatment status, and total and daily costs were recorded. Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program. The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall (annual percentage change, -0.5% and 2.1%, respectively). A total of 10,053 (74.7%) patients underwent surgery. Only 2.8% of patients who underwent surgery did so within 24 hours of injury. A total of 2005 (14.9%) patients were treated with high-dose (≥ 500 mg) methylprednisolone sodium succinate/methylprednisolone (MPSS/MP); 615 (4.6%) received it within 8 hours. The total cost for acute traumatic spinal cord injury decreased over the study period (-4.7%), while daily cost did not significantly change (1.0% increase). Our findings indicate that public health initiatives should aim at improving hospitals' ability to complete early surgery within 24 hours, which is associated with improved sensorimotor recovery, increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

20.
J Clin Ultrasound ; 52(2): 208-218, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38108620

ABSTRACT

PURPOSE: Using visible human, MRI and ultrasound images, we aim to provide an anatomical basis for the identification and diagnosis of pelvic floor structure and disease by ultrasound imaging. METHODS: One Chinese visible human (CVH) image, one American visible human image, 9 MRI images of normal volunteers, and 40 ultrasound images of normal volunteers or pelvic organ prolapse patients were used. Pelvic organs, pelvic floor muscles, and the connective tissue in CVH, VHP, MRI, and ultrasound images were selected for comparative study. RESULTS: We successfully identified the boundary of the anal sphincter complex, including the subcutaneous, superficial, and deep parts of the external anal sphincter, conjoined longitudinal muscles and internal anal sphincter; the levator ani muscle (LAM), including the internal and external parts of the pubovisceral muscle and the superficial and deep parts of the puborectal muscle; the urethral sphincter complex, including the urethral sphincter proper and the urethral compressor; and the perineal body, the rectoperineal muscle and superficial transverse perineal muscle. CONCLUSIONS: We successfully recognized and studied the location, subdivisions, 2D morphology and spatial relationships of the LAM, anal sphincter complex, urethral sphincter complex and perineal body in ultrasound images, thereby helping sonologists or clinicians accurately identify pelvic floor muscles and supporting structures in ultrasound images.


Subject(s)
Anal Canal , Pelvic Floor , Humans , Female , Pelvic Floor/diagnostic imaging , Pelvic Floor/anatomy & histology , Pelvic Floor/physiology , Anal Canal/diagnostic imaging , Muscle, Skeletal , Ultrasonography , Magnetic Resonance Imaging
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