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1.
Front Nutr ; 11: 1378884, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725578

RESUMO

Myofibrillar proteins are an important component of proteins. Flavor characteristics are the key attributes of food quality. The ability of proteins to bind flavor is one of their most fundamental functional properties. The dynamic balance of release and retention of volatile flavor compounds in protein-containing systems largely affects the sensory quality and consumer acceptability of foods. At present, research on flavor mainly focuses on the formation mechanism of flavor components, while there are few reports on the release and perception of flavor components. This review introduces the composition and structure of myofibrillar proteins, the classification of flavor substances, the physical binding and chemical adsorption of myofibrillar proteins and volatile flavor substances, as well as clarifies the regulation law of flavor substances from the viewpoint of endogenous flavor characteristics and exogenous environment factors, to provide a theoretical reference for the flavor regulation of meat products.

2.
Angew Chem Int Ed Engl ; : e202403241, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710651

RESUMO

Exocytosis involving the fusion of intracellular vesicles with cell membrane, is thought to be modulated by the mechanical cues in the microenvironment. Single-cell electrochemistry can offer unique information about the quantification and kinetics of exocytotic events, however, the effects of mechanical force on vesicular release has been poorly explored. Herein, we developed a stretchable microelectrode with excellent electrochemical stability under mechanical deformation by microfabrication of functionalized poly(3,4-ethylenedioxythiophene) conductive ink, which achieved real-time quantitation of strain-induced vesicular exocytosis from a single cell for the first time. We found that mechanical strain could cause calcium influx via the activation of Piezo1 channel in chromaffin cell, initiating the vesicular exocytosis process. Interestingly, mechanical strain increases the amount of catecholamines release by accelerating the opening and prolonging the closing of fusion pore during exocytosis. This work is expected to provide a revealing insight on the regulatory effects of mechanical stimuli on vesicular exocytosis.

3.
Heliyon ; 10(9): e29849, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38699021

RESUMO

Background: Rheumatoid arthritis is a systemic inflammatory autoimmune disease that severely impacts physical and mental health. Autophagy is a cellular process involving the degradation of cellular components in lysosomes. However, from a bioinformatics perspective, autophagy-related genes have not been comprehensively elucidated in rheumatoid arthritis. Methods: In this study, we performed differential analysis of autophagy-related genes in rheumatoid arthritis patients using the GSE93272 dataset from the Gene Expression Omnibus database. Marker genes were screened by least absolute shrinkage and selection operator. Based on marker genes, we used unsupervised cluster analysis to elaborate different autophagy clusters, and further identified modules strongly associated with rheumatoid arthritis by weighted gene co-expression network analysis. In addition, we constructed four machine learning models, random forest model, support vector machine model, generalized linear model and extreme gradient boosting based on marker genes, and based on the optimal machine learning model, a nomogram model was constructed for distinguishing between normal individuals and rheumatoid arthritis patients. Finally, five external independent rheumatoid arthritis datasets were used for the validation of our results. Results: The results showed that autophagy-related genes had significant expression differences between normal individuals and osteoarthritis patients. Through least absolute shrinkage and selection operator screening, we identified 31 marker genes and found that they exhibited significant synergistic or antagonistic effects in rheumatoid arthritis, and immune cell infiltration analysis revealed significant changes in immune cell abundance. Subsequently, we elaborated different autophagy clusters (cluster 1 and cluster 2) using unsupervised cluster analysis. Next, further by weighted gene co-expression network analysis, we identified a brown module strongly associated with rheumatoid arthritis. In addition, we constructed a nomogram model for five marker genes (CDKN2A, TP53, ATG16L2, FKBP1A, and GABARAPL1) based on a generalized linear model (area under the curve = 1.000), and the predictive efficiency and accuracy of this nomogram model were demonstrated in the calibration curves, the decision curves and the five external independent datasets were validated. Conclusion: This study identified marker autophagy-related genes in rheumatoid arthritis and analyzed their impact on the disease, providing new perspectives for understanding the role of autophagy-related genes in rheumatoid arthritis and providing new directions for its individualized treatment.

4.
Gut Microbes ; 16(1): 2351532, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38727248

RESUMO

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.


Assuntos
Microbioma Gastrointestinal , Lipopolissacarídeos , NF-kappa B , Prevotella , Insuficiência Renal Crônica , Transdução de Sinais , Receptor 4 Toll-Like , Calcificação Vascular , Animais , Calcificação Vascular/metabolismo , Calcificação Vascular/patologia , NF-kappa B/metabolismo , Lipopolissacarídeos/metabolismo , Ratos , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/microbiologia , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/patologia , Humanos , Masculino , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Prevotella/metabolismo , Ratos Sprague-Dawley , Miócitos de Músculo Liso/metabolismo , Osteogênese/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Fezes/microbiologia , Inflamassomos/metabolismo
5.
BMC Pediatr ; 24(1): 314, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714985

RESUMO

Aplasia cutis congenita (ACC) is a congenital disorder that can be classified into nine types, with Type I ACC being the most common. Type V ACC associated with fetus papyraceus is a rare subtype of ACC. We report the case of a Type V ACC in a male newborn with extensive abdominal skin defects. The patient received conservative treatment using hydrogel foam and silicone foam dressings. Approximately five weeks later, the patient was discharged when more than 60% of the skin had completed epithelialization. After discharge from West China Second University Hospital, Chengdu , the patient continued to be followed up regularly at the Burns and Plastic Surgery Clinic at local hospital in Gansu. We followed up the child by telephone. After 4 months of follow-up, scar tissue formation was observed in the trunk area. The infant is 2 years and 5 months old now, physical examination did not reveal any organ problems.


Assuntos
Tratamento Conservador , Displasia Ectodérmica , Humanos , Masculino , Displasia Ectodérmica/terapia , Recém-Nascido , Bandagens
6.
Nat Commun ; 15(1): 3902, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724527

RESUMO

Radiation-induced in situ tumor vaccination alone is very weak and insufficient to elicit robust antitumor immune responses. In this work, we address this issue by developing chiral vidarabine monophosphate-gadolinium nanowires (aAGd-NWs) through coordination-driven self-assembly. We elucidate the mechanism of aAGd-NW assembly and characterize their distinct features, which include a negative surface charge, ultrafine topography, and right-handed chirality. Additionally, aAGd-NWs not only enhance X-ray deposition but also inhibit DNA repair, thereby enhancing radiation-induced in situ vaccination. Consequently, the in situ vaccination induced by aAGd-NWs sensitizes radiation enhances CD8+ T-cell-dependent antitumor immunity and synergistically potentiates the efficacy immune checkpoint blockade therapies against both primary and metastatic tumors. The well-established aAGd-NWs exhibit exceptional therapeutic capacity and biocompatibility, offering a promising avenue for the development of radioimmunotherapy approaches.


Assuntos
Nanofios , Polímeros , Nanofios/química , Animais , Camundongos , Polímeros/química , Linhagem Celular Tumoral , Gadolínio/química , Gadolínio/farmacologia , Camundongos Endogâmicos C57BL , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Vacinas Anticâncer/imunologia , Feminino , Humanos , Vacinação/métodos , Neoplasias/imunologia
7.
Transl Oncol ; 44: 101949, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38583352

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Smoking, drinking, and human papillomavirus (HPV) infection are the main risk factors. Early-stage patients can benefit from radical surgery, chemotherapy, and radiotherapy, but the prognosis of locally advanced, recurrent, or metastatic patients is poor. Programmed cell death receptor 1 (PD-1) inhibitor significantly prolongs the survival of these patients, but only about 20 % of the population can benefit significantly. Exploring effective predictive indicators of immunotherapy efficacy and new therapeutic targets is necessary. Tertiary lymphoid structure (TLS) is an ectopic lymphoid organ formed in non-lymphoid tissues, which usually occurs in chronic inflammation including autoimmune diseases, infectious diseases, and tumors. The structure and function of TLS are similar to those of secondary lymphoid organs. The existence of TLS is closely related to the favorable prognosis and immune response of patients. This article will review the formation, prognosis, and predictive value of TLS as well as inducing TLS neogenesis in HNSCC.

8.
World J Gastrointest Oncol ; 16(4): 1180-1191, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38660654

RESUMO

Esophageal cancer ranks among the most prevalent malignant tumors globally, primarily due to its highly aggressive nature and poor survival rates. According to the 2020 global cancer statistics, there were approximately 604000 new cases of esophageal cancer, resulting in 544000 deaths. The 5-year survival rate hovers around a mere 15%-25%. Notably, distinct variations exist in the risk factors associated with the two primary histological types, influencing their worldwide incidence and distribution. Squamous cell carcinoma displays a high incidence in specific regions, such as certain areas in China, where it meets the cost-effectiveness criteria for widespread endoscopy-based early diagnosis within the local population. Conversely, adenocarcinoma (EAC) represents the most common histological subtype of esophageal cancer in Europe and the United States. The role of early diagnosis in cases of EAC originating from Barrett's esophagus (BE) remains a subject of controversy. The effectiveness of early detection for EAC, particularly those arising from BE, continues to be a debated topic. The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses. In areas with higher incidences, such as China and Japan, early diagnosis is more common, which has led to the advancement of endoscopic methods as definitive treatments. These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality. Early screening, prompt diagnosis, and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

9.
J Pediatr (Rio J) ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38642590

RESUMO

OBJECTIVE: To examine the mental health status and related factors in children and adolescents, and to assess age groups and sexes differences in factors influencing mental health. METHODS: This cross-sectional study was performed on Chinese children aged 6-18 years from November 2021 to January 2022. Mental health difficulties were accessed by the Strengths and Difficulties Questionnaire. Multivariate logistic regression was used to analyze factors associated with mental health status. Multiple linear regression was used to evaluate factors associated with the scores of the Strengths and Difficulties Questionnaire. RESULTS: The prevalence of mental health difficulties was 12.98% (n =1348). Age (OR, 0.909, [95%CI, 0.830-0.996]), sex (OR, 1.424, [95%CI, 1.033-1.963]) and screen time on weekdays ("≥2" h/d vs "< 1" h/d: OR, 2.001, [95%CI, 1.300-3.080]) were related factors for mental health difficulties. For children (year ≤ 12), the strongest related factor for mental health difficulties was screen time on weekdays ("≥ 2" h/d vs "< 1" h/d: OR, 1.821 [95%CI, 1.203-2.755]). The risk of mental health difficulties in females with ≥ 2 h/d screen time on weekends was 3.420 times higher than those with < 1 h/d (OR, 3.420, [95%CI, 1.923-6.081]). CONCLUSION: The prevalence of mental health difficulties among children and adolescents was relatively high. The lower age, female sex and excessive screen time were associated with a higher risk of mental health difficulties. The factors influencing mental health varied by different age groups and sexes. Thus, specific measures for different age groups and sexes should be adopted to mitigate the impact.

10.
Soft Matter ; 20(16): 3401-3410, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38563244

RESUMO

Living active collectives have evolved with remarkable self-patterning capabilities to adapt to the physical and biological constraints crucial for their growth and survival. However, the intricate process by which complex multicellular patterns emerge from a single founder cell remains elusive. In this study, we utilize an agent-based model, validated through single-cell microscopy imaging, to track the three-dimensional (3D) morphodynamics of cells within growing bacterial biofilms encased by agarose gels. The confined growth conditions give rise to a spatiotemporally heterogeneous stress landscape within the biofilm. In the core of the biofilm, where high hydrostatic and low shear stresses prevail, cell packing appears disordered. In contrast, near the gel-cell interface, a state of high shear stress and low hydrostatic stress emerges, driving nematic ordering, albeit with a time delay inherent to shear stress relaxation. Strikingly, we observe a robust spatiotemporal correlation between stress anisotropy and nematic ordering within these confined biofilms. This correlation suggests a mechanism whereby stress anisotropy plays a pivotal role in governing the spatial organization of cells. The reciprocity between stress anisotropy and cell ordering in confined biofilms opens new avenues for innovative 3D mechanically guided patterning techniques for living active collectives, which hold significant promise for a wide array of environmental and biomedical applications.


Assuntos
Biofilmes , Estresse Mecânico , Anisotropia , Modelos Biológicos
11.
J Hazard Mater ; 470: 134261, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38608589

RESUMO

Nitrate reduction reaction (NO3RR) is deemed a promising pathway for both ammonia synthesis and water purification. Developing a high-efficiency catalyst with excellent NH3 selectivity and catalytic stability is desirable but remains challenging. In this work, a dendritic copper oxide catalyst (Cu-B2) has been developed to efficiently catalyze NO3RR for ammonia production, the Cu-B2 exhibits excellent catalytic performance, achieving an NH3 Faradaic efficiency as high as 94 % and an NH3 yield of 16.9 mg h-1 cm-2 with a current density of 192.3 mA cm-2 at - 0.6 V (vs. RHE, reversible hydrogen electrode). During NO3RR testing, the Cu-B2 catalysts are reduced in situ to form highly active Cu0/Cu+ sites, while retaining its dendritic morphology. Compared with other catalysts, the Cu-O bond in Cu-B2 catalyst has weaker polarity, resulting in Cu0/Cu+ sites in lower oxidation states. In situ attenuated total reflection surface enhanced infrared absorption spectroscopy (ATR-SEIRAS) studies reveal the Cu-B2 catalyst exhibits a potential-independent capability for *NO3- adsorption and high conversion efficiency of NO2- intermediate into ammonia, DFT calculations reveal that Cu-B2 exhibts higher NO3- adsorption energy and lower NO3- adsorption energy barrier than Cu-B1, thus endowing it with a remarkably improved catalytic activity and durability.

12.
Front Nutr ; 11: 1340453, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559780

RESUMO

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is presently the most prevalent chronic liver disorder globally that is closely linked to obesity, dyslipidemia metabolic syndrome, and type 2 diabetes mellitus (T2DM). Its pathogenesis is strongly associated with inflammation, and diet is a major factor in reducing inflammation. However, current research has focused primarily on exploring the relationship between diet and NAFLD, with less research on its link to MAFLD. Methods: In this research, using dietary inflammatory index (DII) as a measure to assess dietary quality, we analyzed the relationship between diet and MAFLD. Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, including 3,633 adults with complete DII and MAFLD, were used to develop cross-sectional analyses. Logistic regression analysis was adapted for investigating the relationship between DII and MAFLD development. Additionally, subgroup analysis and threshold effect analysis were carried out. Results: A positive link between DII and MAFLD was found in the fully adjusted model (OR = 1.05; 95%CI, 1.00-1.11, p < 0.05). Subgroup analysis indicated that there was no significant dependence for the connection between DII and MAFLD except for the subgroup stratified by age. Compared with other age groups, people with MAFLD had 20% higher DII scores than non-MAFLD participants in those aged 20-41 years old (OR = 1.20; 95%CI, 1.08-1.33, p < 0.001). Furthermore, we found a U-shaped curve with an inflection point of 3.06 illustrating the non-linear connection between DII and MAFLD. Conclusion: As a result, our research indicates that pro-inflammatory diet may increase the chance of MAFLD development, thus improved dietary patterns as a lifestyle intervention is an important strategy to decrease the incidence of MAFLD.

13.
Sci Total Environ ; 929: 172653, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38649053

RESUMO

N,N-dimethylformamide (DMF) is a widely utilized chemical solvent with various industrial applications. Previous studies have indicated that the liver is the most susceptible target to DMF exposure, whereas the underlying mechanisms remain to be elucidated. This study aimed to investigate the role of NLRP3 inflammasome in DMF-induced liver injury in mice by using two NLRP3 inflammasome inhibitors, Nlrp3-/- mice, Nfe2l2-/- mice, and a macrophage-depleting agent. RNA sequencing revealed that endoplasmic reticulum (ER) stress and NLRP3 inflammasome-associated pathways were activated in the mouse liver after acute DMF exposure, which was validated by Western blotting. Interestingly, DMF-induced liver injury was effectively suppressed by two inflammasome inhibitors, MCC950 and Dapansutrile. In addition, knockout of Nlrp3 markedly attenuated DMF-induced liver injury without affecting the metabolism of DMF. Furthermore, silencing Nfe2l2 aggravated the liver injury and the NLRP3 inflammasome activation in mouse liver. Finally, the depletion of hepatic macrophages by clodronate liposomes significantly reduced the liver damage caused by DMF. These results suggest that NLRP3 inflammasome activation is the upstream molecular event in the development of acute liver injury induced by DMF.


Assuntos
Dimetilformamida , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Camundongos , Inflamassomos/metabolismo , Doença Hepática Induzida por Substâncias e Drogas , Fígado/efeitos dos fármacos , Camundongos Knockout , Estresse do Retículo Endoplasmático/efeitos dos fármacos
14.
Sci Rep ; 14(1): 9427, 2024 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658591

RESUMO

Lower-grade gliomas (LGGs) exhibit highly variable clinical behaviors, while classic histology characteristics cannot accurately reflect the authentic biological behaviors, clinical outcomes, and prognosis of LGGs. In this study, we carried out analyses of whole exome sequencing, RNA sequencing and DNA methylation in primary vs. recurrent LGG samples, and also combined the multi-omics data to construct a prognostic prediction model. TCGA-LGG dataset was searched for LGG samples. 523 samples were used for whole exome sequencing analysis, 532 for transcriptional analysis, and 529 for DNA methylation analysis. LASSO regression was used to screen genes with significant association with LGG survival from the frequently mutated genes, differentially expressed genes, and differentially methylated genes, whereby a prediction model for prognosis of LGG was further constructed and validated. The most frequently mutated diver genes in LGGs were IDH1 (77%), TP53 (48%), ATRX (37%), etc. Top significantly up-regulated genes were C6orf15, DAO, MEOX2, etc., and top significantly down-regulated genes were DMBX1, GPR50, HMX2, etc. 2077 genes were more and 299 were less methylated in recurrent vs. primary LGG samples. Thirty-nine genes from the above analysis were included to establish a prediction model of survival, which showed that the high-score group had a very significantly shorter survival than the low-score group in both training and testing sets. ROC analysis showed that AUC was 0.817 for the training set and 0.819 for the testing set. This study will be beneficial to accurately predict the survival of LGGs to identify patients with poor prognosis to take specific treatment as early, which will help improve the treatment outcomes and prognosis of LGG.


Assuntos
Neoplasias Encefálicas , Metilação de DNA , Glioma , Humanos , Glioma/genética , Glioma/patologia , Glioma/mortalidade , Prognóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Mutação , Masculino , Biomarcadores Tumorais/genética , Sequenciamento do Exoma , Gradação de Tumores , Perfilação da Expressão Gênica , Proteína Nuclear Ligada ao X/genética , Pessoa de Meia-Idade , Isocitrato Desidrogenase/genética , Multiômica
15.
BMJ Open ; 14(4): e082957, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580360

RESUMO

INTRODUCTION: Cardiometabolic disease (CMD) is the leading cause of mortality in China. A healthy diet plays an essential role in the occurrence and development of CMD. Although the Chinese heart-healthy diet is the first diet with cardiovascular benefits, a healthy dietary pattern that fits Chinese food culture that can effectively reduce the risk of CMD has not been found. METHODS/DESIGN: The study is a single-centre, open-label, randomised controlled trial aimed at evaluating the effect of the Reducing Cardiometabolic Diseases Risk (RCMDR) dietary pattern in reducing the risk of CMDs in people with dyslipidaemia and providing a reference basis for constructing a dietary pattern suitable for the prevention of CMDs in the Chinese population. Participants are men and women aged 35-45 years with dyslipidaemia in Tianjin. The target sample size is 100. After the run-in period, the participants will be randomised to the RCMDR dietary pattern intervention group or the general health education control group with a 1:1 ratio. The intervention phases will last 12 weeks, with a dietary intervention of 5 working days per week for participants in the intervention group. The primary outcome variable is the cardiometabolic risk score. The secondary outcome variables are blood lipid, blood pressure, blood glucose, body composition indices, insulin resistance and 10-year risk of cardiovascular diseases. ETHICS AND DISSEMINATION: The study complies with the Measures for Ethical Review of Life Sciences and Medical Research Involving Human Beings and the Declaration of Helsinki. Signed informed consent will be obtained from all participants. The study has been approved by the Medical Ethics Committee of the Second Hospital of Tianjin Medical University (approval number: KY2023020). The results from the study will be disseminated through publications in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2300072472).


Assuntos
Doenças Cardiovasculares , Dislipidemias , Masculino , Humanos , Feminino , Padrões Dietéticos , Glicemia , Fatores de Risco , Doenças Cardiovasculares/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
BMC Pulm Med ; 24(1): 207, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671448

RESUMO

OBJECTIVE: The aim of this research was to examine how penehyclidine hydrochloride (PHC) impacts the occurrence of pyroptosis in lung tissue cells within a rat model of lung ischemia-reperfusion injury. METHODS: Twenty-four Sprague Dawley (SD) rats, weighing 250 g to 270 g, were randomly distributed into three distinct groups as outlined below: a sham operation group (S group), a control group (C group), and a test group (PHC group). Rats in the PHC group received a preliminary intravenous injection of PHC at a dose of 3 mg/kg. At the conclusion of the experiment, lung tissue and blood samples were collected and properly stored for subsequent analysis. The levels of malondialdehyde, superoxide dismutase, and myeloperoxidase in the lung tissue, as well as IL-18 and IL-1ß in the blood serum, were assessed using an Elisa kit. Pyroptosis-related proteins, including Caspase1 p20, GSDMD-N, and NLRP3, were detected through the western blot method. Additionally, the dry-to-wet ratio (D/W) of the lung tissue and the findings from the blood gas analysis were also documented. RESULTS: In contrast to the control group, the PHC group showed enhancements in oxygenation metrics, reductions in oxidative stress and inflammatory reactions, and a decrease in lung injury. Additionally, the PHC group exhibited lowered levels of pyroptosis-associated proteins, including the N-terminal segment of gasdermin D (GSDMD-N), caspase-1p20, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3). CONCLUSION: Pre-administration of PHC has the potential to mitigate lung ischemia-reperfusion injuries by suppressing the pyroptosis of lung tissue cells, diminishing inflammatory reactions, and enhancing lung function. The primary mechanism behind anti-pyroptotic effect of PHC appears to involve the inhibition of oxidative stress.


Assuntos
Gasderminas , Pulmão , Piroptose , Quinuclidinas , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Animais , Piroptose/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Ratos , Quinuclidinas/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Masculino , Malondialdeído/metabolismo , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Superóxido Dismutase/metabolismo , Peroxidase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Caspase 1/metabolismo , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/metabolismo
17.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167189, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38648899

RESUMO

OBJECTIVES: Gamete and embryo-foetal origins of adult diseases hypothesis proposes that adulthood chronic disorders are associated with adverse foetal and early life traits. Our study aimed to characterise developmental changes and underlying mechanisms of metabolic disorders in offspring of pre-eclampsia (PE) programmed pregnancy. METHODS: Nω-Nitro-l-arginine methyl ester hydrochloride (L-NAME) induced pre-eclampsia-like C57BL/6J mouse model was used. Lipid profiling, histological morphology, indirect calorimetry, mRNA sequencing, and pyrosequencing were performed on PE offspring of both young and elderly ages. RESULTS: PE offspring exhibited increased postnatal weight gain, hepatic lipid accumulation, enlarged adipocytes, and impaired energy balance that continued to adulthood. Integrated RNA sequencing of foetal and 52-week-old livers revealed that the differentially expressed genes were mainly enriched in lipid metabolism, including glycerol-3-phosphate acyl-transferase 3 (Gpat3), a key enzyme for de novo synthesis of triglycerides (TG), and carnitine palmitoyltransferase-1a (Cpt1a), a key transmembrane enzyme that mediates fatty acid degradation. Pyrosequencing of livers from PE offspring identified hypomethylated and hypermethylated regions in Gpat3 and Cpt1a promoters, which were associated with upregulated and downregulated expressions of Gpat3 and Cpt1a, respectively. These epigenetic alterations are persistent and consistent from the foetal stage to adulthood in PE offspring. CONCLUSION: These findings suggest a methylation-mediated epigenetic mechanism for PE-induced intergenerational lipid accumulation, impaired energy balance and obesity in offspring, and indicate the potential benefits of early interventions in offspring exposed to maternal PE to reduce their susceptibility to metabolic disorder in their later life.

18.
J Int Med Res ; 52(4): 3000605241244763, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38656272

RESUMO

A high systolic/diastolic (S/D) ratio of umbilical cord blood is a manifestation of intrauterine hypoxia. However, the clinical significance of a persistently decreased S/D ratio of umbilical cord blood has not been reported. We report eight cases of a persistently decreased S/D ratio of umbilical cord blood, with two cases of umbilical thrombus, five cases of excessive torsion, and one case of a true cord knot. Fetuses with a persistently decreased S/D ratio of umbilical cord blood may be at risk, and it may be an important indication of umbilical cord lesions.


Assuntos
Diástole , Sangue Fetal , Cordão Umbilical , Adulto , Feminino , Humanos , Masculino , Gravidez , Hipóxia Fetal/diagnóstico , Hipóxia Fetal/fisiopatologia , Sístole/fisiologia , Trombose/diagnóstico , Ultrassonografia Pré-Natal , Cordão Umbilical/patologia
19.
Environ Pollut ; 351: 124061, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38679131

RESUMO

Diffusive gradients in thin films technique (DGT) is recognized as a more reliable method for determining labile heavy metal (HM) concentration in soil than traditional destructive methods. However, the current DGT measurement index, CDGT, theoretically underestimates the true labile concentration (Clabile) of HMs in soil and lacks direct comparability with the conventional soil HM content indices due to unit differences. Here, we proposed CDGT-W, a new simple index which is defined as the HM accumulation in the binding layer, normalized to the weight of soil (optimized water content = 100% of the maximum water holding capacity) filled in the open cavity-type DGT device over a specified deployment time (optimized time = 24 h). The procedure for measuring CDGT-W is analogous to that of CDGT but includes precise determination of water content (water/dry soil) and the mass of soil filled in the cavity. We conducted measurements of Cu, Pb, Cr(Ⅵ) and As(V) as CDGT-W, CDGT, solution concentration (Csoln), and CaCl2 extractable concentration (CCaCl2) on three soils with a diverse range of HM concentrations. CDGT-W showed significant linear correlations with all other tested indexes. The ratios of CDGT-W to CCaCl2 varied between 0.30 and 0.98 for all HM-soil combinations with only one exception, a range much greater than CDGT/Csoln (typically <0.1) but lower than 1. This suggested that CDGT-W may more accurately reflect Clabile than CDGT (theoretically underestimates Cliable) and CCaCl2(likely overestimates Cliable). Additionally, CDGT-W measurements for these four HMs exhibited a broad measure concentration range and a low detection limit (mg/kg level). Consequently, CDGT-W may offer a more reliable alternative to CDGT for characterizing Clabile in unsaturated soils.

20.
Curr Med Imaging ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38676517

RESUMO

Standard multidetector computed tomography (MDCT) uses a single X-ray tube to emit a mixed energy X-ray beam, which is received by a single detector. The difference is that dual-energy CT (DECT), a new equipment in recent years, employs a single X-ray tube or two X-ray tubes to emit two single-energy X-ray beams, which are received by a single or two detectors. The application of dual-energy technology to portal venography has become one of the research hotspots. This paper will elaborate on the clinical application values of DECT portal venography in improving portal vein image quality, distinguishing the nature of portal vein thrombus, reducing contrast agent dose and radiation dose, and will discuss the possibility of its movement from research to routine practice and future development opportunities.

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