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1.
Front Pediatr ; 12: 1416189, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39296668

RESUMO

Mycoplasma pneumoniae is the primary pathogen causing community-acquired pneumonia in children, accounting for approximately 10%-40% of cases. It can lead to various extrapulmonary complications, including acute pancreatitis, which has been reported in approximately 30 cases to date. Here, we report a 4-year-old girl who presented with fever, cough, and elevated levels of M. pneumoniae IgM antibodies, followed by the onset of abdominal pain, elevated lipase, and elevated blood and urine amylase. Abdominal CT implied diffuse inflammation of the pancreas. Serum inflammatory cytokines, such as interleukin (IL)-2, IL-6, IL-17A, tumor necrosis factor, and interferon-gamma, were elevated. After excluding other causes, it was determined that M. pneumoniae infection was the cause of her acute pancreatitis. She was treated with macrolides and glucocorticoids and ultimately made a full recovery. Therefore, acute pancreatitis should be included in the differential diagnosis for patients with M. pneumoniae infection who present with abdominal pain. Inflammatory cytokines may play a role in mediating pancreatic damage.

2.
Int J Biol Macromol ; 279(Pt 2): 135290, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39233178

RESUMO

Fungal keratitis (FK) is recognized as a stubborn ocular condition, caused by intense fungal invasiveness and heightened immune reaction. The glycosaminoglycan chondroitin sulfate exhibits properties of immunomodulation and tissue regeneration. In prior investigations, oxidized chondroitin sulfate (OCS) ameliorated the prognosis of FK in murine models. To further improve the curative efficacy, we used the antifungal drug natamycin to functionalize OCS and prepared oxidized chondroitin sulfate-natamycin (ON) eye drops. The structure of ON was characterized by FTIR, UV-vis, and XPS, revealing that the amino group of natamycin combined with the aldehyde group in OCS through Schiff base reaction. Antifungal experiments revealed that ON inhibited fungal growth and disrupted the mycelium structure. ON exhibited exceptional biocompatibility and promoted the proliferation of corneal epithelial cells. Pharmacokinetic analysis indicated that ON enhanced drug utilization by extending the mean residence time in tears. In murine FK, ON treatment reduced the clinical score and corneal fungal load, restored corneal stroma conformation, and facilitated epithelial repair. ON effectively inhibited neutrophil infiltration and decreased the expression of TLR-4, LOX-1, IL-1ß, and TNF-α. Our research demonstrated that ON eye drops achieved multifunctional treatment for FK, including inhibiting fungal growth, promoting corneal repair, enhancing drug bioavailability, and controlling inflammatory reactions.


Assuntos
Anti-Inflamatórios , Antifúngicos , Sulfatos de Condroitina , Ceratite , Natamicina , Soluções Oftálmicas , Animais , Natamicina/farmacologia , Natamicina/química , Natamicina/administração & dosagem , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Camundongos , Soluções Oftálmicas/química , Soluções Oftálmicas/farmacologia , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacologia , Antifúngicos/farmacologia , Antifúngicos/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Modelos Animais de Doenças , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia
3.
J Biomater Appl ; : 8853282241280844, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39208309

RESUMO

OBJECTIVE: Fungal keratitis (FK) usually develops to a poor clinical prognosis due to the fungal invasion and excessive inflammatory reaction. In order to enhance the therapeutic effect of natamycin (NAT), we used the anti-inflammatory biological polysaccharide bletilla striata polysaccharide (BSP) combined with NAT to prepare a new eye drop -- oxidized bletilla striata polysaccharide-natamycin (OBN). METHODS: UV-vis, FT-IR, and fluorescence spectroscopy were used to identify the synthesis of OBN. Biocompatibility of OBN was determined by CCK-8, scratch assay, and corneal toxicity test. RAW264.7 cells and C57BL/6 mice were stimulated with A. fumigatus and treated with PBS, OBN, or NAT. The anti-inflammatory activity of OBN was detected by RT-PCR and ELISA. In mice with FK, the clinical scores were used to evaluate the effect of OBN; HE staining was performed to assess the corneal pathological changes; MPO assay and immunofluorescence staining were used to investigate neutrophil infiltration. RESULTS: OBN was synthesized by combining oxidized bletilla striata polysaccharide (OBSP) with NAT through Schiff base reaction. OBN did not affect cell viability at a concentration of 160 µg/mL in HCECs, RAW264.7 cells, and mouse corneas. OBN versus NAT significantly improved the prognosis of A. fumigatus keratitis by reducing disease severity, neutrophil infiltration, and expression of inflammatory factors in vivo. Additionally, OBN treatment down-regulated the mRNA and protein expression levels of inflammatory factors IL-1ß, TNF-α, and IL-6 in RAW264.7 and mouse models. CONCLUSION: OBN is a compound prepared by covalently linking OBSP to the imino group of NAT through Schiff base reaction. OBN treatment down-regulated inflammation and improved the prognosis of mice with A. fumigatus keratitis.

4.
Alpha Psychiatry ; 25(3): 362-368, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39148600

RESUMO

Objective: The prevalence of depression in children with severe bronchial asthma is a significant concern due to its potential effects on illness burden and quality of life. This cross-sectional study aims to explore the relationship between depression and severe bronchial asthma in children, focusing on the impact of alexithymia and somatic symptoms. Methods: The study includes a total of 186 children aged 6-14 years diagnosed with severe bronchial asthma between 2008 and 2022 in our institute. Alexithymia was assessed using the Toronto Alexithymia Scale-20 items (TAS-20). Somatization symptoms were measured using the children's somatization inventory (CSI). The Hamilton depression scale (HAMD) was used to evaluate depression. Spearman correlation analysis was used to describe the correlation between alexithymia, somatization symptoms, and depression. Results: Children with bronchial asthma are found to have a significantly higher prevalence of depression, estimated to be around 16.67%. Approximately 98.92% of children exhibit varying degrees of somatic symptoms. Approximately 3.23% of children have alexithymia. The Spearman correlation analysis revealed that somatic symptoms and alexithymia were positive correlated with the depression. The correlation coefficients were 0.986 and 0.981 (P < .01), respectively. moreover, according to the results of multiple linear regression analysis, somatization symptoms and alexithymia significantly affects depression in children with severe bronchitis asthma (P < .01). Conclusion: These findings suggest that children with severe bronchial asthma experience a higher prevalence of depression, impacting their overall quality of life. In addition, the presence of somatic symptoms is prevalent among these children, further contributing to the burden on their quality of life. Moreover, somatization symptoms and alexithymia have been identified as a significant factor positive affecting depression in this population. Addressing these factors in clinical interventions may be beneficial for improving the overall well-being in this population.

5.
Plant Physiol Biochem ; 208: 108472, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38442627

RESUMO

Brassinosteroids (BR) play crucial roles in plant development and abiotic stresses in plants. Exogenous application of BR can significantly enhance cold tolerance in rice. However, the regulatory relationship between cold tolerance and the BR signaling pathway in rice remains largely unknown. Here, we characterized functions of the BR receptor OsBRI1 in response to cold tolerance in rice using its loss-of-function mutant (d61-1). Our results showed that mutant d61-1 was less tolerant to cold stress than wild-type (WT). Besides, d61-1 had lower levels than WT for some physiological parameters, including catalase activity (CAT), superoxide dismutase activity (SOD), peroxidase activity (POD), peroxidase activity (PRO), soluble protein, and soluble sugar content, while malondialdehyde content (MDA) and relative electrical conductivity (REC) levels in d61-1 were higher than those in WT plants. These results indicated that the loss of OsBRI1 function resulted in decreased cold tolerance in rice. In addition, we performed RNA sequencing (RNA-seq) of WT and d61-1 mutant under cold stress. Numerous common and unique differentially expressed genes (DEGs) with up- and down-regulation were observed in WT and d61-1 mutant. Some DEGs were expressed to various degrees, even opposite, between CK1 vs. T1 (WT) and CK2 vs. T2 (d61-1). Among these specific DEGs, some typical genes are involved in plant tolerance to cold stress. Through weighted correlation network analysis (WGCNA), 50 hub genes were screened in the turquoise and blue module. Many genes were involved in cold stress and plant hormone, such as Os01g0279800 (BRI1-associated receptor kinase 1 precursor), Os10g0513200 (Dwarf and tiller-enhancing 1, DTE1), Os02g0706400 (MYB-related transcription factor, OsRL3), etc. Differential expression levels of some genes were verified in WT and d61-1 under cold stress using qRT-PCR. These valuable findings and gene resources will be critical for understanding the regulatory relationships between cold stress tolerance and the BR signaling pathways in rice.


Assuntos
Brassinosteroides , Oryza , Brassinosteroides/farmacologia , Brassinosteroides/metabolismo , Oryza/metabolismo , Perfilação da Expressão Gênica , Resposta ao Choque Frio/genética , Peroxidases , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo
6.
J Hazard Mater ; 469: 133815, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38428294

RESUMO

Molten salt pyrolysis technology stands out as a potent approach for achieving efficient degradation and energy recovery of composite organic materials. Nevertheless, challenges such as the high melting point of molten salt, product destruction, and the complexities of treating waste salt pose significant limitations to the widespread application and popularization of this technology. To tackle these issues, this study proposes a salt-assisted pyrolysis method based on capillary heat transfer called permeable liquid salt pyrolysis. Focusing on abandoned power industry insulators, the research delves into the thermal and mass transfer model of cluster-embedded materials under non-molten salt conditions. The investigation reveals that the capillary between glass fiber and resin proves beneficial in enhancing heat transfer conditions by creating a novel phase known as permeate liquid. Results demonstrate that salt-assisted pyrolysis can substantially lower the required temperature and enhance the pyrolysis reaction rate, achieving a maximum degradation efficiency of 98.99 %. Additionally, the pyrolysis products undergo in-situ modification, with a notable reduction in benzene series compounds ranging from 68 % to 85 %. Furthermore, an erosion diffusion capillary mode is established. This study presents an environmentally-friendly approach to recycle and modify products derived from waste resin-based composite materials generated in the electric power industry.

7.
Cancer Immunol Immunother ; 73(4): 75, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38532108

RESUMO

BACKGROUND: CD47, serving as an intrinsic immune checkpoint, has demonstrated efficacy as an anti-tumor target in hematologic malignancies. Nevertheless, the clinical relevance of CD47 in gastric cancer and its potential as a therapeutic target remains unclear. METHODS: The expression of CD47 in clinical gastric cancer tissues was assessed using immunohistochemistry and Western blot. Patient-derived cells were obtained from gastric cancer tissues and co-cultured with macrophages derived from human peripheral blood mononuclear cells. Flow cytometry analyses were employed to evaluate the rate of phagocytosis. Humanized patient-derived xenografts (Hu-PDXs) models were established to assess the efficacy of anti-CD47 immunotherapy or the combination of anti-CD47 and anti-VEGF therapy in treating gastric cancer. The infiltrated immune cells in the xenograft were analyzed by immunohistochemistry. RESULTS: In this study, we have substantiated the high expression of CD47 in gastric cancer tissues, establishing a strong association with unfavorable prognosis. Through the utilization of SIRPα-Fc to target CD47, we have effectively enhanced macrophage phagocytosis of PDCs in vitro and impeded the growth of Hu-PDXs. It is noteworthy that anti-CD47 immunotherapy has been observed to sustain tumor angiogenic vasculature, with a positive correlation between the expression of VEGF and CD47 in gastric cancer. Furthermore, the successful implementation of anti-angiogenic treatment has further augmented the anti-tumor efficacy of anti-CD47 therapy. In addition, the potent suppression of tumor growth, prevention of cancer recurrence after surgery, and significant prolongation of overall survival in Hu-PDX models can be achieved through the simultaneous targeting of CD47 and VEGF using the bispecific fusion protein SIRPα-VEGFR1 or by combining the two single-targeted agents. CONCLUSIONS: Our preclinical studies collectively offer substantiation that CD47 holds promise as a prospective target for gastric cancer, while also highlighting the potential of anti-angiogenic therapy to enhance tumor responsiveness to anti-CD47 immunotherapy.


Assuntos
Neoplasias , Neoplasias Gástricas , Animais , Humanos , Antígeno CD47 , Modelos Animais de Doenças , Imunoterapia , Leucócitos Mononucleares/metabolismo , Recidiva Local de Neoplasia , Fagocitose , Fator A de Crescimento do Endotélio Vascular
8.
J Ocul Pharmacol Ther ; 40(1): 89-99, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38346287

RESUMO

Purpose: To characterize the efficiency of glabridin alone and in combination with clinical antifungals in Aspergillus fumigatus keratitis. Methods: The broth microdilution method was performed to investigate whether glabridin exerted an antifungal role on planktonic cells and immature and mature biofilm. Antifungal mechanism was evaluated by Sorbitol and Ergosterol Assays. The synergistic effect of glabridin and antifungals was assessed through the checkerboard microdilution method and time-killing test. Regarding anti-inflammatory role, inflammatory substances induced by A. fumigatus were assessed by real-time quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay. Drug toxicity was assessed by Draize test in vivo. Macrophage phenotypes were examined by flow cytometry. Results: Regarding antifungal activity, glabridin destroyed fungal cell wall and membrane on planktonic cells and suppressed immature and mature biofilm formation. After combining with natamycin or amphotericin B, glabridin possessed a potent synergistic effect against A. fumigatus. Regarding anti-inflammatory aspects, Dectin-1, toll­like receptor (TLR)-2 and TLR-4 expression of human corneal epithelial cells were significantly elevated after A. fumigatus challenge and reduced by glabridin. The elevated expression of interleukin-1ß and tumor necrosis factor-alpha induced by A. fumigatus or corresponding agonists were reversed by glabridin, equivalent to the effect of corresponding inhibitors. Glabridin could also contribute to anti-inflammation by downregulating inflammatory mediator expression to suppress macrophage infiltration. Conclusions: Glabridin contributed to fungal clearance by destroying fungal cell wall and membrane, and disrupting biofilm. Combining glabridin with clinical antifungals was superior in reducing A. fumigatus growth. Glabridin exerted an anti-inflammatory effect by downregulating proinflammatory substance expression and inhibiting macrophage infiltration, which provide a potential agent and treatment strategies for fungal keratitis.


Assuntos
Aspergilose , Infecções Oculares Fúngicas , Isoflavonas , Ceratite , Fenóis , Humanos , Animais , Camundongos , Aspergillus fumigatus/fisiologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Camundongos Endogâmicos C57BL
9.
Brain Behav Immun ; 117: 270-282, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38211635

RESUMO

Parkinson's disease (PD) is intricately linked to abnormal gut microbiota, yet the specific microbiota influencing clinical outcomes remain poorly understood. Our study identified a deficiency in the microbiota genus Blautia and a reduction in fecal short-chain fatty acid (SCFA) butyrate level in PD patients compared to healthy controls. The abundance of Blautia correlated with the clinical severity of PD. Supplementation with butyrate-producing bacterium B. producta demonstrated neuroprotective effects, attenuating neuroinflammation and dopaminergic neuronal death in mice, consequently ameliorating motor dysfunction. A pivotal inflammatory signaling pathway, the RAS-related pathway, modulated by butyrate, emerged as a key mechanism inhibiting microglial activation in PD. The change of RAS-NF-κB pathway in PD patients was observed. Furthermore, B. producta-derived butyrate demonstrated the inhibition of microglial activation in PD through regulation of the RAS-NF-κB pathway. These findings elucidate the causal relationship between specific gut microbiota and PD, presenting a novel microbiota-based treatment perspective for PD.


Assuntos
Clostridiales , Microbiota , Doença de Parkinson , Humanos , Animais , Camundongos , Microglia , Doenças Neuroinflamatórias , NF-kappa B , Butiratos
10.
Sci Total Environ ; 916: 170306, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38272096

RESUMO

Microplastics (MPs) is a novel and significant pollution due to its eco-environmental hazards and ubiquity. In end-of-life vehicle (ELV) recycling base, MPs are widely distributed but have rare reported in scientific literature. In this study, a comprehensive analysis of MPs was conducted in a typical ELV recycling base. MPs were found in all samples at different sampling sites and environmental mediums. A total of 34 polymer types were detected by µ-FTIR, and the main polymers include PE-PP, ABS, polyester resin, nylon, and PEU plastic. MPs were released from the crushing, tearing, and breaking of plastic parts in ELVs. They were in high content in ground dust, with the abundance of 737-29,021 p/5 g D (the average abundance of 5552 ± 6435 p/5 g D). The abundance, shape, color, and size of MPs are related with functional areas of ELV recycling. Heavy metals could be adsorbed on MPs, and their contents on MPs have a significant correlation with those in the corresponding dust samples. At last, some specific MPs control measures, such as changing transportation mode, using dust-proof cloths, and equipping dust removal equipment, have been put forward.

11.
Sci Total Environ ; 912: 169609, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38157917

RESUMO

The disposal of end-of-life vehicles (ELVs) is an issue of great concern to the society, because of its huge amount, resource value and environmental pollution. A wide variety of pollutants generate and release during the recycling process. However, previous studies are piecemeal and segmentary, the correlation between treatment flowchart and pollution is unknown, and pollution source analysis in ELV recycling and core parts (engine, gear box, etc.) remanufacturing bases is still a challenge. In this study, the aim is to propose a green strategy for upcycling utilization of ELV part based on pollution source analysis, technology flowchart, and technology upgrade. We synthetically analyzed current typical ELV dismantling and core part remanufacturing processes of ELVs. A total of 36 volatile organic compound (VOC) species and 7 heavy metals were found in dismantling process, and 61 VOC species were detected in remanufacturing process. Based on statistical analysis and treatment process characteristics, 18 pollution fingerprints were constructed. At last, an intelligent dismantling and upcycle utilization line for ELVs has been developed to improve production efficiency and reduce pollution release.

12.
Environ Sci Technol ; 57(49): 20941-20950, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38032848

RESUMO

Bromine removal is significant in the recycling of waste printed circuit boards (WPCBs). This study found that the critical factors limiting the debromination efficiency of conventional pyrolysis are the formation of coke impeding mass transfer and conversion of bromine into less volatile species, such as coking-Br and copper bromide. According to frontier molecular orbital analysis and thermodynamic equilibrium analysis, C-O bonds of resin are sites prone to electrophilic reactions and copper bromide in residue may undergo hydrolysis; therefore, introducing H2O during pyrolysis was a feasible method for thorough debromination. Through pyrolysis in a water vapor atmosphere, the diffusion limitation of debromination was overcome, and resin was converted into light components; thereby, rapid and deep removal of bromine was achieved. The result indicated that 99.7% of bromine was removed, and the residue could be used as a clean secondary resource. According to life-cycle assessment, pyrolysis of WPCBs in water vapor could be expected to reduce 77 Kt of CO2 emission and increase financial benefits by 60 million dollars, annually.


Assuntos
Resíduo Eletrônico , Vapor , Cobre , Bromo/química , Brometos , Pirólise , Reciclagem/métodos , Resíduo Eletrônico/análise
13.
Front Oncol ; 13: 1214413, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37771444

RESUMO

Background: Studies have shown that the immune infiltration of tumor microenvironment is related to the prognosis of glioblastoma, which is characterized by high heterogeneity, high recurrence rate and low survival rate. To unravel the role of ß1,3-N-acetylglucosaminyltransferase-9 (ß3GNT9) in the progression of glioblastoma, this study identifies the value of ß3GNT9 as a prognostic biomarker in glioblastoma, and investigates the relationship between ß3GNT9 expression and glioblastoma immune infiltration, migration and invasion. Methods: ß3GNT9 expression in glioblastoma was analyzed using the GEPIA database. The clinical features of glioblastoma were screened out from the TCGA database. The relationship between ß3GNT9 expression and clinical features was analyzed. The relationship between ß3GNT9 and the prognosis of glioblastoma was evaluated through univariate and multivariate COX regression analyses, and the survival analysis was conducted using the Kaplan-Meier method. GSEA was employed to predict the signaling pathway of ß3GNT9 in glioblastoma. The correlation between ß3GNT9 and tumor immune infiltration was analyzed using the related modules of CIBERSORT and TIMER. A172, U87MG and U251 cell lines were selected to verify ß3GNT9 expression in vitro. The effects of ß3GNT9 on the migration and invasion of glioblastoma were investigated through cell scratch and invasion assays. Results: ß3GNT9 expression in glioblastoma group was significantly higher than that in normal brain tissue group (P<0.05). The overall survival rate in high ß3GNT9 expression group was significantly lower than that in low ß3GNT9 expression group (P<0.05). Regression analyses suggested that ß3GNT9, involved primarily in glucosamine degradation and extracellular matrix receptor interaction, could be an independent prognostic factor for glioblastoma. CIBERSORT and GEPIA database analyses showed that ß3GNT9 was correlated with tumor infiltrating immune cells such as T follicular helper cells, activating natural killer cells, monocytes, macrophages, and eosinophils, thus affecting the immune microenvironment of glioblastoma. Cell experiments confirmed that ß3GNT9 was highly expressed in A172, U87MG and U251 cell lines (P<0.05), and promoted the migration and invasion of glioblastoma (P<0.05). Conclusion: The increased expression of ß3GNT9 in glioblastoma can affect the immune microenvironment of glioblastoma and promote its migration and invasion. ß3GNT9 can be used as a potential independent prognostic biomarker for patients with glioblastoma.

14.
Cytokine ; 171: 156356, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37677994

RESUMO

PURPOSE: To investigate the antifungal and anti-inflammatory effects of quercetin in Aspergillus fumigatus (A. fumigatus) keratitis. METHODS: Draize eye test was performed in mice to evaluate the toxicity of quercetin, and the antifungal effects on A. fumigatus were assessed via scanning electron microscopy (SEM), propidium iodide uptake, and adherence assay. In fungal keratitis (FK) mouse models, immunostaining was performed for investigating toll-like receptor 4 (TLR-4) expression and macrophage infiltration. Real-time PCR, ELISA, and Western blot were used to evaluate the expression of pro-inflammatory factors IL-1ß, TNF-α, and IL-6 in infected RAW264.7 cells. Cells were also treated with TLR-4 siRNA or agonist CRX-527 to investigate mechanisms underlying the anti-inflammatory activity of quercetin. RESULTS: Quercetin at 32 µM was non-toxic to corneal epithelial and significantly inhibited A. fumigatus growth and adhesion, and also altered the structure and reduced the number of mycelia. Quercetin significantly reduced macrophage infiltration in the mouse cornea, and attenuated the expression of TLR-4 in the corneal epithelium and stroma of mice with keratitis caused by A. fumigatus. In RAW264.7 cells infected by A. fumigatus, quercetin downregulated TLR-4 along with pro-inflammatory factors IL-1ß, TNF-α, and IL-6. RAW cells with TLR-4 knockdown had reduced expression of factors after A. fumigatus infection, which was decreased even further with quercetin treatment. In contrast, cells with CRX-527 had elevated inflammatory factors compared to control, which was significantly attenuated in the presence of quercetin. CONCLUSION: Quercetin plays a protective role in mouse A. fumigatus keratitis by inhibiting fungal load, disrupting hyphae structure, macrophage infiltration, and suppressing inflammation response in macrophages via TLR-4 mediated signaling pathway.


Assuntos
Aspergillus fumigatus , Ceratite , Camundongos , Animais , Receptor 4 Toll-Like , Quercetina/farmacologia , Antifúngicos/uso terapêutico , Interleucina-6 , Fator de Necrose Tumoral alfa/uso terapêutico , Ceratite/tratamento farmacológico , Ceratite/metabolismo , Ceratite/microbiologia , Anti-Inflamatórios/uso terapêutico , Camundongos Endogâmicos C57BL
15.
Front Pharmacol ; 14: 1257450, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37693915

RESUMO

Colorectal cancer (CRC) is the third most common malignant tumor in the world, and it is prone to recurrence and metastasis during treatment. Aerobic glycolysis is one of the main characteristics of tumor cell metabolism in CRC. Tumor cells rely on glycolysis to rapidly consume glucose and to obtain more lactate and intermediate macromolecular products so as to maintain growth and proliferation. The regulation of the CRC glycolysis pathway is closely associated with several signal transduction pathways and transcription factors including phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), hypoxia-inducible factor-1 (HIF-1), myc, and p53. Targeting the glycolytic pathway has become one of the key research aspects in CRC therapy. Many phytochemicals were shown to exert anti-CRC activity by targeting the glycolytic pathway. Here, we review the effects and mechanisms of phytochemicals on CRC glycolytic pathways, providing a new method of drug development.

16.
Environ Pollut ; 337: 122570, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37717900

RESUMO

Owing to the large amount of waste glass generated, the waste glass recycling base is an indispensable municipal supporting facility of a sustainable city. However, waste glass recycling is a complex process involving stages such as multiple-stage crushing and material sorting. Consequently, waste glass recycling base has a considerable impact on the surrounding environment, such as health risk of particulate matter on workers. In this study, we aimed to perform a comprehensive investigation and analysis of compound pollution characteristics and health risk evaluation of particulate matter and heavy metals generated from waste glass recycling process. Soil, particulate fallout, and glass samples were collected from inside and outside a recycling plant in eastern China. Our findings showed that the waste glass treatment process produces a large amount of air particulate matter, and the PM2.5 and PM10 concentrations can reach 3725 and 4055 µg/m3, respectively, in the production workshop during working hours. Meanwhile, the monitoring results show that the concentration of heavy metals on fine particles is higher compared to coarse particles. The high Zn and Pb concentrations detected in the soil and dustfall were proved to be derived from the glass raw materials. However, health risk assessment and particle deposition modeling in the human respiratory system revealed that heavy metals from the air particulate matter have no significant carcinogenicity or non-carcinogenic risk. The Gaussian dispersion model showed that the impact of particulate matter on the surrounding environment and health of the surrounding residents is minimal. Furthermore, transportation is the major emission link according to the particulate emission calculation, indicating that it is imperative to upgrade and reform the existing processes of waste glass recycling. Taken together, this study provides a scientific basis for the green development of waste glass recycling process and further environmental information regarding waste glass recycling plants.


Assuntos
Resíduo Eletrônico , Metais Pesados , Humanos , Material Particulado/análise , Metais Pesados/análise , Poluição Ambiental/análise , Poeira/análise , China , Medição de Risco , Reciclagem , Solo , Carvão Mineral/análise , Monitoramento Ambiental/métodos , Resíduo Eletrônico/análise
17.
Sci Total Environ ; 891: 164233, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37225105

RESUMO

In recent years, the rapid development of technology has posed significant challenges to the waste management practices of the retired vehicle industry. How to minimize the environmental impact during the recycle process of scrap vehicle has emerged as a prevalent and pressing concern. This study employed statistical analysis and positive matrix factorization (PMF) model to assess the origin of Volatile Organic Compounds (VOCs) at a scrap vehicle dismantling location situated in China. The quantification of potential hazards to human health arising from identified sources was achieved through the integration of source characteristics with exposure risk assessment. In addition, fluent simulation was employed to examine the spatiotemporal dispersion of the pollutant concentration field and velocity profile. The findings of the study revealed that the activities of parts cutting, disassembling air conditioning and refined dismantling were responsible for 89.98 %, 84.36 %, and 78.63 % of the total air pollution accumulation, respectively. Additionally, it should be noted that the aforementioned sources accounted for 59.40 %, 18.44 %, and 4.86 % of the aggregate non-cancer risk. The cumulative cancer risk was determined to be the disassembling air conditioning process, with a contribution of 82.71 %. Meanwhile, the average concentration of VOC in soil around the disassembling air conditioning area is 8.4 times higher than the background value. The simulation revealed that pollutants were primarily dispersed within the factory at a height ranging from 0.75 m to 2 m, which corresponds to the human respiratory zone and the concentration of pollutants in the vehicle cutting area was observed to exceed normal levels by over 10 times. These findings of this study may serve as a foundation for improving of environmental protection measures of industrialization.

18.
Front Public Health ; 11: 1142794, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37006569

RESUMO

Background: Home and community-based services are considered an appropriate and crucial caring method for older adults in China. However, the research examining demand for medical services in HCBS through machine learning techniques and national representative data has not yet been carried out. This study aimed to address the absence of a complete and unified demand assessment system for home and community-based services. Methods: This was a cross-sectional study conducted on 15,312 older adults based on the Chinese Longitudinal Healthy Longevity Survey 2018. Models predicting demand were constructed using five machine-learning methods: Logistic regression, Logistic regression with LASSO regularization, Support Vector Machine, Random Forest, and Extreme Gradient Boosting (XGboost), and based on Andersen's behavioral model of health services use. Methods utilized 60% of older adults to develop the model, 20% of the samples to examine the performance of models, and the remaining 20% of cases to evaluate the robustness of the models. To investigate demand for medical services in HCBS, individual characteristics such as predisposing, enabling, need, and behavior factors constituted four combinations to determine the best model. Results: Random Forest and XGboost models produced the best results, in which both models were over 80% at specificity and produced robust results in the validation set. Andersen's behavioral model allowed for combining odds ratio and estimating the contribution of each variable of Random Forest and XGboost models. The three most critical features that affected older adults required medical services in HCBS were self-rated health, exercise, and education. Conclusion: Andersen's behavioral model combined with machine learning techniques successfully constructed a model with reasonable predictors to predict older adults who may have a higher demand for medical services in HCBS. Furthermore, the model captured their critical characteristics. This method predicting demands could be valuable for the community and managers in arranging limited primary medical resources to promote healthy aging.


Assuntos
Serviços de Saúde Comunitária , Serviços de Saúde , Humanos , Idoso , Estudos Transversais , Necessidades e Demandas de Serviços de Saúde , Aprendizado de Máquina
19.
J Cancer ; 14(3): 350-359, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36860925

RESUMO

Patients with gastric cancer liver metastasis (GCLM) are often treated with palliative care, and they show a poor prognosis. In gastric cancer, high CD47 expression has been shown to indicate a poor prognosis. CD47, expressed on the cell surface, prevents the cells from being phagocytosed by macrophages. Anti-CD47 antibodies have been shown to be effective in the treatment of metastatic leiomyosarcoma. Nonetheless, the role of CD47 in GCLM has not yet been elucidated. Here, we showed that CD47 expression in GCLM tissues was higher than that in situ. Moreover, we demonstrated that high CD47 expression correlated with an adverse prognosis. Accordingly, we investigated the role of CD47 in the development of GCLM in mouse liver. Knockdown of CD47 inhibited GCLM development. Furthermore, in vitro engulfment assays showed that decreased CD47 expression led to an increased phagocytic activity of Kupffer cells (KCs). Using enzyme-linked immunosorbent assay, we determined that CD47 knockdown promoted cytokine secretion by macrophages. Furthermore, we found that tumor-derived exosomes decreased KC-mediated phagocytosis of gastric cancer cells. Finally, in a heterotopic xenograft model, the administration of anti-CD47 antibodies inhibited tumor growth. In addition, as 5-fluorouracil (5-Fu)-based chemotherapy is the cornerstone in GCLM treatment, we administered a combination of anti-CD47 antibodies and 5-Fu, which acted synergistically to suppress the tumor. Overall, we demonstrated that tumor-derived exosomes are involved in GCLM progression, targeting CD47 inhibits gastric cancer tumorigenesis, and a combination of anti-CD47 antibodies and 5-Fu shows potential for treating GCLM.

20.
Int Immunopharmacol ; 118: 109849, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36933490

RESUMO

PURPOSE: To screen and identify the mechanism of honokiol on anti-fungi and anti-inflammation in fungal keratitis (FK) through bioinformatic analysis and biological experiments. METHODS: Transcriptome profile demonstrated differential expression genes (DEGs) of Aspergillus fumigatus keratitis between PBS-treated and honokiol-treated groups via bioinformatics analyses. Inflammatory substances were quantified by qRT-PCR, Western blot and ELISA, and macrophage polarization was examined by flow cytometry. Periodic acid Schiff staining and morphological interference assay were used to detect hyphal distribution in vivo and fungal germination in vitro, respectively. Electron microscopy was to illustrate hyphal microstructure. RESULTS: Illumina sequencing demonstrated that compared with the honokiol group, 1175 up-regulated and 383 down-regulated genes were induced in C57BL/6 mice Aspergillus fumigatus keratitis with PBS treatment. Through GO analysis, some differential expression proteins (DEPs) played major roles in biological processes, especially fungal defense and immune activation. KEGG analysis provided fungus-related signaling pathways. PPI analysis demonstrated that DEPs from multiple pathways form a close-knit network, providing a broader context for FK treatment. In biological experiments, Dectin-2, NLRP3 and IL-1ß were upregulated by Aspergillus fumigatus to evaluate immune response. Honokiol could reverse the trend, comparable to Dectin-2 siRNA interference. Meanwhile, honokiol could also play an anti-inflammatory role via promoting M2 phenotype polarization. Moreover, honokiol reduced hyphal distribution in the stroma, delayed germination, and destroyed the hyphal cell membrane in-vitro. CONCLUSIONS: Honokiol possesses anti-fungal and anti-inflammatory effects in Aspergillus fumigatus keratitis and may develop a potential and safe therapeutic modality for FK.


Assuntos
Aspergilose , Infecções Oculares Fúngicas , Ceratite , Animais , Camundongos , Aspergillus fumigatus , Regulação para Baixo , Camundongos Endogâmicos C57BL , Inflamação/tratamento farmacológico , Infecções Oculares Fúngicas/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
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