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1.
Anal Chim Acta ; 1314: 342781, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38876519

RESUMO

BACKGROUND: Okadaic acid (OA), as a diarrhetic shellfish poisoning, can increase the risk of acute carcinogenic or teratogenic effects for the ingestion of OA contaminated shellfish. At present, much effort has been made to graft immunoassay onto a paper substrate to make paper-based sensors for rapid and simple detection of shellfish toxin. However, the complicated washing steps and low protein fixation efficiency on the paper substrate need to be further addressed. RESULTS: A novel paper-tip immunosensor for detecting OA was developed combined with smartphone and naked eye readout. The trapezoid paper tip was consisted of quantitative and qualitative detection zones. To improve the OA antigen immobilization efficiency on the paper substrate, graphene oxide (GO)-assisted protein immobilization method was introduced. Meanwhile, Au nanoparticles composite probe combined with the lateral flow washing was developed to simplify the washing step. The OA antigen-immobilized zone, as the detection zone Ⅰ, was used for quantitative assay by smartphone imaging. The paper-tip front, as the detection zone Ⅱ, which could qualitatively differentiate OA pollution level within 45 min using the naked eye. The competitive immunoassay on the paper tip exhibited a wide linear range for detecting OA (0.02-50 ng∙mL-1) with low detection limit of 0.02 ng∙mL-1. The recovery of OA in spiked shellfish samples was in the range of 90.3 %-113.%. SIGNIFICANCE: These results demonstrated that the proposed paper-tip immunosensor could provide a simple, low-cost and high-sensitivity test for OA detection without the need for additional large-scale equipment or expertise. We anticipate that this paper-tip immunosensor will be a flexible and versatile tool for on-site detecting the pollution of marine products.


Assuntos
Técnicas Biossensoriais , Ouro , Grafite , Ácido Okadáico , Papel , Smartphone , Grafite/química , Ácido Okadáico/análise , Imunoensaio/métodos , Ouro/química , Nanopartículas Metálicas/química , Proteínas Imobilizadas/química , Limite de Detecção , Animais , Anticorpos Imobilizados/imunologia , Anticorpos Imobilizados/química
2.
Int J Biol Sci ; 20(8): 2922-2942, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38904021

RESUMO

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and the production of autoantibodies. Previous studies have indicated an association between high-salt diets (HSD) and an increased risk of RA, yet the underlying mechanisms remain unclear. Macrophage pyroptosis, a pro-inflammatory form of cell death, plays a pivotal role in RA. In this study, we demonstrate that HSD exacerbates the severity of arthritis in collagen-induced arthritis (CIA) mice, correlating with macrophage infiltration and inflammatory lesions. Given the significant alterations observed in macrophages from CIA mice subjected to HSD, we specifically investigate the impact of HSD on macrophage responses in the inflammatory milieu of RA. In our in vitro experiments, pretreatment with NaCl enhances LPS-induced pyroptosis in RAW.264.7 and THP-1 cells through the p38 MAPK/NF-κB signaling pathway. Subsequent experiments reveal that Slc6a12 inhibitors and SGK1 silencing inhibit sodium-induced activation of macrophage pyroptosis and the p38 MAPK/NF-κB signaling pathway, whereas overexpression of the SGK1 gene counteracts the effect of sodium on macrophages. In conclusion, our findings verified that high salt intake promotes the progression of RA and provided a detailed elucidation of the activation of macrophage pyroptosis induced by sodium transportation through the Slc6a12 channel.


Assuntos
Artrite Reumatoide , Macrófagos , Proteínas Serina-Treonina Quinases , Piroptose , Animais , Camundongos , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Macrófagos/metabolismo , Piroptose/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Cloreto de Sódio/farmacologia , Células RAW 264.7 , Humanos , Masculino , Proteínas Imediatamente Precoces/metabolismo , Proteínas Imediatamente Precoces/genética , Artrite Experimental/metabolismo , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Camundongos Endogâmicos DBA
3.
4.
Int J Mol Sci ; 25(12)2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38928337

RESUMO

3-(4-Hydroxy-3-methoxyphenyl)propionic acid (HMPA), also known as dihydroferulic acid, is a hydroxycinnamic acid derivative that can be derived from the microbial transformation of dietary polyphenols or naturally obtained from fermented foods. Although numerous studies have documented its antioxidant and anti-obesity effects, the effect of HMPA on muscle function remains unknown. This study investigated the effects of HMPA on muscle strength and exercise endurance capacity. Mice were orally administered low and high doses of HMPA for 14 days and subjected to grip force and treadmill exhaustion tests to evaluate muscle function. Our results showed that HMPA-administered groups significantly enhanced absolute grip strength (p = 0.0256) and relative grip strength (p = 0.0209), and low-dose HMPA decreased the plasma level of blood urea nitrogen after exercise (p = 0.0183), but HMPA did not affect endurance performance. Low-dose HMPA administration increased Myf5 expression in sedentary mice (p = 0.0106), suggesting that low-dose HMPA may promote muscle development. Additionally, HMPA improved hepatic glucose and lipid metabolism, and inhibited muscular lipid metabolism and protein catabolism, as indicated by changes in mRNA expression levels of related genes. These findings suggest that HMPA may be a promising dietary supplement for muscle health and performance.


Assuntos
Músculo Esquelético , Condicionamento Físico Animal , Animais , Camundongos , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Propionatos/farmacologia , Força da Mão , Força Muscular/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos
5.
Cell Rep ; 43(6): 114350, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38870013

RESUMO

Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its gene regulatory programs and the low diagnostic yield of tumor biopsies due to spatial heterogeneity. Herein, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries from tissue and plasma samples from 50 patients with RCC and healthy volunteers. By profiling histone modifications and DNA methylation, we identified highly recurrent epigenomic reprogramming enriched in sRCC. Furthermore, CRISPRa experiments implicated the transcription factor FOSL1 in activating sRCC-associated gene regulatory programs, and FOSL1 expression was associated with the response to ICIs in RCC in two randomized clinical trials. Finally, we established a blood-based diagnostic approach using detectable sRCC epigenomic signatures in patient plasma, providing a framework for discovering epigenomic correlates of tumor histology via liquid biopsy.


Assuntos
Carcinoma de Células Renais , Epigenômica , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Epigenômica/métodos , Metilação de DNA/genética , Diferenciação Celular , Regulação Neoplásica da Expressão Gênica , Masculino , Feminino , Epigênese Genética , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-fos
6.
Anal Chem ; 96(24): 9761-9766, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38887087

RESUMO

This Technical Note describes a dual-column liquid chromatography system coupled to mass spectrometry (LC-MS) for high-throughput bottom-up proteomic analysis. This system made full use of two 2-position 10-port valves and a binary pump with an integrated loading pump of a commercial LC instrument to provide successive operation of two parallel subsystems. Each subsystem consisted of a set of trap columns and an analytical column. A T-junction union was used to split the mobile phase from the loading pump into two parts. This allowed one set of columns to be washed and equilibrated, followed by the injection of the next sample, while the previous sample was eluting and being analyzed on the other set of columns, thereby greatly increasing the analysis throughput. This approach showed high reproducibility for the analysis of HeLa tryptic digests with average relative standard deviation (RSD) values of 1.75%, 6.90%, and 5.19% for the identification number of proteins, peptides, and peptide-spectrum matches (PSMs), respectively, across 10 consecutive runs. The capacity for peptide and protein identification, as well as proteome depth, of the dual-column LC system was comparable to a conventional single-column system. Due to its simple equipment requirements and set up process, this method should be highly accessible for other laboratories.


Assuntos
Espectrometria de Massas , Proteômica , Proteômica/métodos , Humanos , Células HeLa , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Automação , Ensaios de Triagem em Larga Escala , Peptídeos/análise , Espectrometria de Massa com Cromatografia Líquida
7.
J Adv Res ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38879122

RESUMO

INTRODUCTION: Metabolic inflammation (metaflammation) in obesity is primarily initiated by proinflammatory macrophage infiltration into adipose tissue. SelenoM contributes to the modulation of antioxidative stress and inflammation in multiple pathological processes; however, its roles in metaflammation and the proinflammatory macrophage (M1)-like state in adipose tissue have not been determined. OBJECTIVES: We hypothesize that SelenoM could effectively regulate metaflammation via the Hippo-YAP/TAZ-ROS signaling axis in obesity derived from a high-fat diet. METHODS: Morphological changes in adipose tissue were examined by hematoxylin-eosin (H&E) staining and fluorescence microscopy. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were used to evaluate the impact of SelenoM deficiency on blood glucose levels. RNA-Seq analysis, LC-MS analysis, Mass spectrometry analysis and western blotting were performed to detect the levels of genes and proteins related to glycolipid metabolism in adipose tissue. RESULTS: Herein, we evaluated the inflammatory features and metabolic microenvironment of mice with SelenoM-deficient adipose tissues by multi-omics analyses. The deletion of SelenoM resulted in glycolipid metabolic disturbances and insulin resistance, thereby accelerating weight gain, adiposity, and hyperglycemia. Mice lacking SelenoM in white adipocytes developed severe adipocyte hypertrophy via impaired lipolysis. SelenoM deficiency aggravated the generation of ROS by reducing equivalents (NADPH and glutathione) in adipocytes, thereby promoting inflammatory cytokine production and the M1-proinflammatory reaction, which was related to a change in nuclear factor kappa-B (NF-κB) levels in macrophages. Mechanistically, SelenoM deficiency promoted metaflammation via Hippo-YAP/TAZ-ROS-mediated transcriptional regulation by targeting large tumor suppressor 2 (LATS2). Moreover, supplementation with N-acetyl cysteine (NAC) to reduce excessive oxidative stress partially rescued adipocyte inflammatory responses and macrophage M1 activation. CONCLUSION: Our data indicate that SelenoM ameliorates metaflammation mainly via the Hippo-YAP/TAZ-ROS signaling axis in obesity. The identification of SelenoM as a key regulator of metaflammation presents opportunities for the development of novel therapeutic interventions targeting adipose tissue dysfunction in obesity.

8.
J Med Chem ; 67(9): 7569-7584, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38690687

RESUMO

PTP1B, a promising target for insulin sensitizers in type 2 diabetes treatment, can be effectively degraded using proteolysis-targeting chimera (PROTAC). This approach offers potential for long-acting antidiabetic agents. We report potent bifunctional PROTACs targeting PTP1B through the E3 ubiquitin ligase cereblon. Western blot analysis showed significant PTP1B degradation by PROTACs at concentrations from 5 nM to 5 µM after 48 h. Evaluation of five highly potent PROTACs revealed compound 75 with a longer PEG linker (23 atoms), displaying remarkable degradation activity after 48 and 72 h, with DC50 values of 250 nM and 50 nM, respectively. Compound 75 induced selective degradation of PTP1B, requiring engagement with both the target protein and CRBN E3 ligase, in a ubiquitination and proteasome-dependent manner. It significantly reduced blood glucose AUC0-2h to 29% in an oral glucose tolerance test and activated the IRS-1/PI3K/Akt signaling pathway in HepG2 cells, showing promise for long-term antidiabetic therapy.


Assuntos
Hipoglicemiantes , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Proteólise , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Descoberta de Drogas , Células Hep G2 , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/síntese química , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteólise/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ubiquitina-Proteína Ligases/metabolismo
9.
Physiol Plant ; 176(3): e14320, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38686642

RESUMO

Many nucleoside triphosphate-diphosphohydrolases (NTPDases/APYRASEs, APYs) play a key role in modulating extracellular nucleotide levels. However, the Golgi-localized APYs, which help control glycosylation, have rarely been studied. Here, we identified AtAPY1, a gene encoding an NTPDase in the Golgi apparatus, which is required for cell wall integrity and plant growth under boron (B) limited availability. Loss of function in AtAPY1 hindered cell elongation and division in root tips while increasing the number of cortical cell layers, leading to swelling of the root tip and abundant root hairs under low B stress. Further, expression pattern analysis revealed that B deficiency significantly induced AtAPY1, especially in the root meristem and stele. Fluorescent-labeled AtAPY1-GFP localized to the Golgi stack. Biochemical analysis showed that AtAPY1 exhibited a preference of UDP and GDP hydrolysis activities. Consequently, the loss of function in AtAPY1 might disturb the homoeostasis of NMP-driven NDP-sugar transport, which was closely related to the synthesis of cell wall polysaccharides. Further, cell wall-composition analysis showed that pectin content increased and borate-dimerized RG-II decreased in apy1 mutants, along with a decrease in cellulose content. Eventually, altered polysaccharide characteristics presumably cause growth defects in apy1 mutants under B deficiency. Altogether, these data strongly support a novel role for AtAPY1 in mediating responses to low B availability by regulating cell wall integrity.


Assuntos
Apirase , Proteínas de Arabidopsis , Arabidopsis , Boro , Parede Celular , Complexo de Golgi , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/enzimologia , Arabidopsis/metabolismo , Parede Celular/metabolismo , Boro/metabolismo , Boro/deficiência , Complexo de Golgi/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Apirase/metabolismo , Apirase/genética , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Meristema/genética , Meristema/crescimento & desenvolvimento , Meristema/metabolismo , Pectinas/metabolismo
10.
Environ Sci Pollut Res Int ; 31(17): 26089-26098, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492135

RESUMO

Polybrominated diphenyl ethers (PBDEs) are toxic to organisms with melatonin (MT) providing protection for tissues and cells against these. This study investigates the mechanism of damage of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and the cellular protection of MT on grass carp hepatocytes. Grass carp hepatocytes were exposed to 25 µmol/L BDE-47 and/or 40 µmol/L MT for 24 h before testing. Acridine orange/ethidium bromide (AO/EB) double fluorescence staining results showed that BDE-47 could induce cell apoptosis. The expression levels of the endoplasmic reticulum (ER) stress-related genes ire1, atf4, grp78, perk, and chop were also significantly up-regulated (P < 0.01). The levels of the apoptosis-related genes caspase3, bax, and caspase9 were significantly up-regulated (P < 0.0001), while the level of bcl-2 was significantly down-regulated (P < 0.01). Compared with the BDE-47 group, the BDE-47 + MT group showed reduced levels of ER and apoptosis of hepatocytes, while the expression of the ER stress-related genes ire1, atf4, grp78, perk, and chop and the apoptosis-related genes caspase3, bax, and caspase9 were down-regulated (P < 0.05), and the level of bcl-2 was up-regulated (P < 0.01). In conclusion, BDE-47 can activate ER and apoptosis in grass carp hepatocytes, while MT can reduce these responses.


Assuntos
Carpas , Melatonina , Animais , Éteres Difenil Halogenados/metabolismo , Melatonina/metabolismo , Proteína X Associada a bcl-2/metabolismo , Chaperona BiP do Retículo Endoplasmático , Hepatócitos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Apoptose , Proteínas Serina-Treonina Quinases/metabolismo , Estresse do Retículo Endoplasmático
11.
Sex Transm Dis ; 51(4): 289-294, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38430512

RESUMO

BACKGROUND: Men who have sex with men (MSM) are at increased risk for human papillomavirus-associated oropharyngeal cancer (HPV-OPC). The objective of this analysis was to create a psychometrically validated scale to measure perception of risk for HPV-OPC. METHODS: We conducted an exploratory and a confirmatory factor analysis to determine and confirm the latent factor structure. We used a path diagram to evaluate the relationship between the validated scale and perceived risk for HPV-OPC. The model was determined to be a good fit if it met all criteria: root mean square error of approximation ≤0.06, standardized root mean residual ≤0.08, Comparative Fit Index ≥0.90, and Tucker-Lewis Index ≥0.90. We report standardized estimates and 95% confidence intervals. RESULTS: This cross-sectional study recruited 1315 MSM. A majority (73.33%) of MSM had performed fellatio on ≥20 partners, 36.98% had rimmed ≥20 partners, and 5.31% had performed cunnilingus on ≥10 partners in their lifetime.Six sexual history survey items loaded onto 2 latent factors: sexual risk behaviors: class 1 and sexual risk behaviors: class 2. The final model statistics indicated good fit: root mean square error of approximation = 0.064, standardized root mean residual = 0.059, Comparative Fit Index = 0.996, and Tucker-Lewis Index = 0.993. Sexual risk behaviors: class 1 was associated with greater perceived risk for HPV-OPC (0.217; 95% confidence interval, 0.138-0.295). Age, HIV status, HPV vaccination status, and sexual risk behaviors: class 2 were not associated with perceived risk for HPV-OPC. CONCLUSION: Men who have sex with men assessed risk for HPV-OPC based on their lifetime number of cisgender male sexual partners, rimming partners, and fellatio partners but not other sexual behaviors. Men who have sex with men may be responsive to future HPV-OPC educational interventions and opportunities for screening.


Assuntos
Infecções por HIV , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Estudos Transversais , Psicometria , Comportamento Sexual , Fatores de Risco
12.
Genome Med ; 16(1): 22, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317189

RESUMO

BACKGROUND: Although polygenic risk score (PRS) has emerged as a promising tool for predicting cancer risk from genome-wide association studies (GWAS), the individual-level accuracy of lung cancer PRS and the extent to which its impact on subsequent clinical applications remains largely unexplored. METHODS: Lung cancer PRSs and confidence/credible interval (CI) were constructed using two statistical approaches for each individual: (1) the weighted sum of 16 GWAS-derived significant SNP loci and the CI through the bootstrapping method (PRS-16-CV) and (2) LDpred2 and the CI through posteriors sampling (PRS-Bayes), among 17,166 lung cancer cases and 12,894 controls with European ancestry from the International Lung Cancer Consortium. Individuals were classified into different genetic risk subgroups based on the relationship between their own PRS mean/PRS CI and the population level threshold. RESULTS: Considerable variances in PRS point estimates at the individual level were observed for both methods, with an average standard deviation (s.d.) of 0.12 for PRS-16-CV and a much larger s.d. of 0.88 for PRS-Bayes. Using PRS-16-CV, only 25.0% of individuals with PRS point estimates in the lowest decile of PRS and 16.8% in the highest decile have their entire 95% CI fully contained in the lowest and highest decile, respectively, while PRS-Bayes was unable to find any eligible individuals. Only 19% of the individuals were concordantly identified as having high genetic risk (> 90th percentile) using the two PRS estimators. An increased relative risk of lung cancer comparing the highest PRS percentile to the lowest was observed when taking the CI into account (OR = 2.73, 95% CI: 2.12-3.50, P-value = 4.13 × 10-15) compared to using PRS-16-CV mean (OR = 2.23, 95% CI: 1.99-2.49, P-value = 5.70 × 10-46). Improved risk prediction performance with higher AUC was consistently observed in individuals identified by PRS-16-CV CI, and the best performance was achieved by incorporating age, gender, and detailed smoking pack-years (AUC: 0.73, 95% CI = 0.72-0.74). CONCLUSIONS: Lung cancer PRS estimates using different methods have modest correlations at the individual level, highlighting the importance of considering individual-level uncertainty when evaluating the practical utility of PRS.


Assuntos
Estratificação de Risco Genético , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Teorema de Bayes , Estudo de Associação Genômica Ampla , Incerteza , Medição de Risco , Fatores de Risco , Predisposição Genética para Doença
13.
Sci Rep ; 14(1): 4753, 2024 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413665

RESUMO

This study aimed to probe into the anatomic course of inferior alveolar nerve canal (IANC) in hemifacial microsomia (HFM) on a large scale, morphological observations and further quantitative study were performed. Patients were classified by Pruzansky-Kaban classification. The anatomic course of IANC was analyzed morphologically with three-dimensional (3D) imaging software among 248 patients. Seven distances between fixed landmarks on both sides were measured for 236 patients. The differences between affected and unaffected sides were compared. Significant differences were found in the entrance (P < 0.001), route (P < 0.001), and exit (P < 0.05) of IANC in type IIb and III HFM. The higher the degree of mandibular deformity was, the higher the incidence of IANC variation was (P < 0.05). The distances in the horizontal aspect of IANC including from mandibular foramen to mental foramen (P < 0.05) and from mental foramen to gonion (P < 0.05) were significantly shorter on the affected side. Abnormalities of the anatomical course of IANC exist in patients with Pruzansky-Kaban type IIb and type III HFM. The reduction of IANC on the affected side in the horizontal distance is more obvious. Three-dimensional imaging assessment is recommended before surgery.


Assuntos
Síndrome de Goldenhar , Humanos , Tomografia Computadorizada por Raios X/métodos , Mandíbula/diagnóstico por imagem , Imageamento Tridimensional/métodos , Nervo Mandibular/diagnóstico por imagem
14.
J Agric Food Chem ; 72(7): 3741-3754, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38340082

RESUMO

Decabromodiphenyl ether (BDE-209) is a widely used brominated flame retardant that can easily detach from materials and enter into feed and foodstuffs, posing a serious risk to human and animal health and food safety of animal origin. However, the immunotoxic effects of BDE-209 on the avian spleen and the exact mechanism of the toxicity remain unknown. Therefore, we established an experimental model of BDE-209-exposed chickens and a positive control model of cyclophosphamide-induced immunosuppression in vivo and treated MDCC-MSB-1 cells and chicken splenic primary lymphocytes with BDE-209 in vitro. The results showed that BDE-209 treatment caused morphological and structural abnormalities in the chicken spleens. Mechanistically, indicators related to oxidative stress, endoplasmic reticulum stress (ERS), autophagy, and apoptosis were significantly altered by BDE-209 exposure in both the spleen and lymphocytes, but the use of the N-acetylcysteine or the 4-phenylbutyric acid significantly reversed these changes. In addition, BDE-209 exposure decreased the spleen antimicrobial peptide and immunoglobulin gene expression. In conclusion, the present research revealed that BDE-209 exposure enhanced lymphocyte autophagy and apoptosis in chicken spleen via the ROS-mediated ERS pathway. This signaling cascade regulatory relationship not only opens up a new avenue for studying BDE-209 immunotoxicity but also provides important insights into preventing BDE-209 hazards to animal health.


Assuntos
Galinhas , Retardadores de Chama , Humanos , Animais , Galinhas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Baço/metabolismo , Éteres Difenil Halogenados/toxicidade , Éteres Difenil Halogenados/metabolismo , Apoptose , Autofagia , Estresse do Retículo Endoplasmático , Retardadores de Chama/toxicidade
15.
Acad Radiol ; 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38233260

RESUMO

Pathophysiologic changes in lung diseases are often accompanied by changes in ventilation and gas exchange. Comprehensive evaluation of lung function cannot be obtained through chest X-ray and computed tomography. Proton-based lung MRI is particularly challenging due to low proton density within the lung tissue. In this review, we discuss an emerging technology--hyperpolarized gas MRI with inhaled 129Xe, which provides functional and microstructural information and has the potential as a clinical tool for detecting the early stage and progression of certain lung diseases. We review the hyperpolarized 129Xe MRI studies in patients with a range of pulmonary diseases, including chronic obstructive pulmonary disease, asthma, cystic fibrosis, pulmonary hypertension, radiation-induced lung injury and interstitial lung disease, and the applications of artificial intelligence were reviewed as well.

16.
Aquat Toxicol ; 267: 106839, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38228041

RESUMO

The surfactant perfluorooctane sulfonate (PFOS) is widely produced worldwide. It is a persistent organic pollutant in the aquatic environment and poses a serious threat to aquatic organisms, as PFOS exposure can cause liver injury in a wide range of organisms. However, it is unclear whether PFOS exposure-induced hepatocellular injury in fish is associated with ROS-mediated activation of NLRP3 inflammasome. In this study, various PFOS concentrations were applied to L8824 cells, a cell line of grass carp hepatocytes. The detrimental impacts of PFOS on oxidative stress, pyroptosis, lipid metabolism, and the discharge of inflammatory factors were examined. MCC950 and N-acetylcysteine were employed to hinder the PFOS-stimulated activation of the NLRP3 inflammasome and the excessive generation of reactive oxygen species in L8824 cells, respectively. This study demonstrated that treatment with PFOS resulted in oxidative stress and activation of NLRP3 inflammasome in L8824 cells. This led to increased expression levels of indicators related to pyroptosis, accompanied by the upregulation of pro-inflammatory cytokine expression as well as downregulation of anti-inflammatory factors. In addition, following PFOS exposure, the expression levels of genes related to lipid synthesis were upregulated and lipid catabolism-related genes were downregulated. Surprisingly, both N-acetylcysteine and MCC950 interventions significantly reduced PFOS-induced L8824 cell pyroptosis and lipid metabolism disorders. In conclusion, this research demonstrated that PFOS drives NLRP3 inflammasome activation through oxidative stress induced by reactive oxygen species overload. This in turn leads to pyroptosis and lipid metabolism disorders.


Assuntos
Fluorocarbonos , Transtornos do Metabolismo dos Lipídeos , Poluentes Químicos da Água , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Metabolismo dos Lipídeos , Piroptose , Acetilcisteína/farmacologia , Poluentes Químicos da Água/toxicidade , Hepatócitos/metabolismo , Transtornos do Metabolismo dos Lipídeos/metabolismo , Lipídeos
17.
Int J Nanomedicine ; 19: 727-742, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38288265

RESUMO

Background: A sequential release co-delivery system is an effective strategy to improve anti-cancer efficacy. Herein, multicomponent-based liposomes (TET-CTM/L) loaded with tetrandrine (TET) and celastrol (CEL)-loaded coix seed oil microemulsion (CTM) were fabricated, which showed synergistic anti-liver cancer activities. By virtue of Enhanced Permeability and Retention (EPR) effect, TET-CTM/L can achieve efficient accumulation at the tumor site. TET was released initially to repair abnormal vessels and decrease the fibroblasts, and CTM was released subsequently for eradication of tumor tissue. Methods: TEM (transmission electron microscopy) and DLS (dynamic light scattering) were adopted to characterize the TET-CTM/L. Flow cytometry was adopted to examine the cellular uptake and cytotoxicity of HepG2 cells. The HepG2 xenograft nude mice were adopted to evaluate the anti-tumor efficacy and systemic safety of TET-CTM/L. Results: TEM images of TET-CTM/L showed the structure of small particle size of CTM within large-size liposomes, indicating that CTM can be encapsulated in liposomes by film dispersion method. In in vitro studies, TET-CTM/L induced massive apoptosis toward HepG2 cells, indicating synergistic cytotoxicity against HepG2 cells. In in vivo studies, TET-CTM/L displayed diminished systemic toxicity compared to celastrol or TET used alone. TET-CTM/L showed the excellent potential for tumor-targeting ability in a biodistribution study. Conclusion: Our study provides a new strategy for combining anti-cancer therapy that has good potential not only in the treatment of liver cancer but also can be applied to the treatment of other solid tumors.


Assuntos
Benzilisoquinolinas , Coix , Neoplasias Hepáticas , Triterpenos Pentacíclicos , Animais , Camundongos , Humanos , Lipossomos , Coix/química , Camundongos Nus , Distribuição Tecidual , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Óleos de Plantas/química
18.
Trials ; 25(1): 42, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216974

RESUMO

BACKGROUND: Mandibular distraction osteogenesis (MDO) is a major part of the treatment for hemifacial microsomia patients. Due to the narrow surgical field of the intraoral approach, osteotomy accuracy is highly dependent on the surgeons' experience. Electromagnetic (EM) tracking systems can achieve satisfying accuracy to provide helpful real-time surgical navigation. Our research team developed an EM navigation system based on artificial intelligence, which has been justified in improving the accuracy of osteotomy in the MDO in animal experiments. This study aims to clarify the effect of the EM navigation system in improving the MDO accuracy for hemifacial microsomia patients. METHODS: This study is designed as a single-centered and randomized controlled trial. Altogether, 22 hemifacial microsomia patients are randomly assigned to the experiment and control groups. All patients receive three-dimensional CT scans and preoperative surgical plans. The EM navigation system will be set up for those in the experiment group, and the control group will undergo traditional surgery. The primary outcome is the surgical precision by comparing the osteotomy position of pre- and postoperative CT scan images through the Geomagic Control software. The secondary outcomes include mandibular symmetry (occlusal plane deviation angle, mandibular ramus height, and body length), pain scale, and complications. Other indications, such as the adverse events of the system and the satisfactory score from patients and their families, will be recorded. DISCUSSION: This small sample randomized controlled trial intends to explore the application of an EM navigation system in MDO for patients, which has been adopted in other surgeries such as orthognathic procedures. Because of the delicate structures of children and the narrow surgical view, accurate osteotomy and protection of nearby tissue from injury are essential for successful treatment. The EM navigation system based on artificial intelligence adopted in this trial is hypothesized to provide precise real-time navigation for surgeons and optimally improve patient outcomes, including function and aesthetic results. The results of this trial will extend the application of new navigation technology in pediatric plastic surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200061565. Registered on 29 June 2022.


Assuntos
Síndrome de Goldenhar , Osteogênese por Distração , Criança , Humanos , Pré-Escolar , Adolescente , Síndrome de Goldenhar/diagnóstico por imagem , Síndrome de Goldenhar/cirurgia , Inteligência Artificial , Osteogênese por Distração/efeitos adversos , Osteogênese por Distração/métodos , Método Simples-Cego , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Sci Total Environ ; 915: 170129, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38242456

RESUMO

Decabromodiphenyl ether (BDE-209) is one of the most widely used flame retardants that can infect domestic and wildlife through contaminated feed. Nano­selenium (Nano-Se) has the advantage of enhancing the anti-oxidation of cells. Nonetheless, it remains uncertain whether Nano-Se can alleviate vascular Endothelial cells damage caused by BDE-209 exposure in chickens. Therefore, we established a model with 60 1-day-old chickens, and administered BDE-209 intragastric at a ratio of 400 mg/kg bw/d, and mixed Nano-Se intervention at a ratio of 1 mg/kg in the feed. The results showed that BDE-209 could induce histopathological and ultrastructural changes. Additionally, exposure to BDE-209 led to cardiovascular endoplasmic reticulum stress (ERS), oxidative stress and thioredoxin-interacting protein (TXNIP)-pyrin domain-containing protein 3 (NLRP3) pathway activation, ultimately resulting in pyroptosis. Using the ERS inhibitor 4-PBA in Chicken arterial endothelial cells (PAECs) can significantly reverse these changes. The addition of Nano-Se can enhance the body's antioxidant capacity, inhibit the activation of NLRP3 inflammasome, and reduce cellular pyroptosis. These results suggest that Nano-Se can alleviate the pyroptosis of cardiovascular endothelial cells induced by BDE-209 through ERS-TXNIP-NLRP3 pathway. This study provides new insights into the toxicity of BDE-209 in the cardiovascular system and the therapeutic effects of Nano-Se.


Assuntos
Sistema Cardiovascular , Éteres Difenil Halogenados , Selênio , Animais , Células Endoteliais/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Galinhas/metabolismo , Piroptose , Selênio/metabolismo , Estresse do Retículo Endoplasmático
20.
J Plast Reconstr Aesthet Surg ; 88: 112-118, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37972441

RESUMO

BACKGROUND: Patients requiring plastic surgery exhibit more abnormal psychological trends (e.g., body dysmorphic disorder [BDD], depression, and anxiety) than those requiring other surgeries. However, there are only a few domestic studies on the psychological aspects of the population requiring plastic surgery. Therefore, we analyzed the psychological characteristics and psychological impact of rhinoplasty in female patients. METHODS: In this study, patients were classified into 2 groups: 151 males and 60 females. The self-rating scale of body image (SSBI), self-rating anxiety scale, self-rating depression scale, and postoperative satisfaction questionnaire were used to examine the patients before and after surgery. The results were analyzed using t-test, analysis of variance, chi-square test, paired rank sum test, and Pearson correlation analysis. RESULTS: The total prevalence of BDD in female patients who underwent rhinoplasty was 7.3%. The prevalence of anxiety disorders was 31.8% and that of depression was 45.0%. Female patients with BDD were more likely to exhibit depression (55.5%) and anxiety (36.4%). The SSBI score was related to marital status (p = 0.001) and history of rhinoplasty (p = 0.000). Moreover, there was a significant negative correlation between preoperative BDD score and postoperative satisfaction (r = -0.392, p = 0.002) as well as between the previous history of rhinoplasty and postoperative satisfaction (r = -0.603, p = 0.000). CONCLUSION: Pathological psychologies such as anxiety, depression, and BDD are common in patients scheduled to undergo rhinoplasty, and BDD is more likely to be associated with depression. Rhinoplasty has little psychological impact on patients, i.e., it neither causes improvement nor deterioration. Female patients who have undergone rhinoplasty should be considered to a have high risk of BDD. Although the outcomes of surgery are generally quite positive, patients diagnosed with BDD are more likely to be dissatisfied.


Assuntos
Transtornos Dismórficos Corporais , Procedimentos de Cirurgia Plástica , Rinoplastia , Cirurgia Plástica , Masculino , Humanos , Feminino , Rinoplastia/psicologia , Transtornos Dismórficos Corporais/diagnóstico , Transtornos Dismórficos Corporais/epidemiologia , Transtornos Dismórficos Corporais/psicologia , Imagem Corporal/psicologia , Inquéritos e Questionários
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