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1.
J Transl Med ; 22(1): 983, 2024 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-39482719

RESUMEN

BACKGROUND: Hyperuricemia is independently associated with a poor prognosis in patients with myocardial infarction (MI). Furthermore, MI induces activation of the repair response in local fibroblasts, resulting in extracellular matrix accumulation that generates a stable fibrotic scar in the infarcted area. However, researchers have not determined whether hyperuricemia affects fibroblast activation and its involvement in postinfarction cardiac remodeling. OBJECTIVES: We aimed to trigger hyperuricemia by administering potassium oxonate in a mouse model of MI to evaluate the role of hyperuricemia in MI pathogenesis. METHODS: Microarray datasets and single-cell sequencing data from gout patients, heart failure patients, and model mice were used to identify the underlying mechanisms responsible for the effect of hyperuricemia on MI progression. A hyperuricemia-related MI mouse model was established. Cardiac function was assessed, followed by sample collection and a uric acid assay. We conducted an enzyme-linked immunosorbent assay, histological detection, immunofluorescence, sequencing data processing, single-cell RNA-seq, and functional enrichment analysis. We then isolated and cultured cardiac fibroblasts and performed Western blotting, quantitative real-time polymerase chain reaction, and shRNA-mediated lumican knockdown assays. RESULTS: Hyperuricemia decreased cardiac function, increased mortality, and aggravated adverse fibrosis remodeling in mice after MI. These outcomes were closely related to reduced levels of fibroblast-derived lumican. This reduction activated the TGF-ß/SMAD signaling pathway to induce aberrant myofibroblast activation and extracellular matrix deposition in the infarcted area. Furthermore, lumican supplementation or uric acid-lowering therapy with allopurinol alleviated hyperuricemia-mediated abnormal cardiac remodeling. CONCLUSION: Hyperuricemia aggravates postinfarction cardiac remodeling by reducing lumican expression and promoting fibroblast phenotype transition. We highlight the clinical importance of lowering uric acid levels in hyperuricemia-related MI to prevent adverse ventricular remodeling.


Asunto(s)
Fibroblastos , Hiperuricemia , Lumican , Ratones Endogámicos C57BL , Infarto del Miocardio , Fenotipo , Remodelación Ventricular , Animales , Hiperuricemia/complicaciones , Hiperuricemia/patología , Infarto del Miocardio/patología , Infarto del Miocardio/complicaciones , Fibroblastos/metabolismo , Fibroblastos/patología , Lumican/metabolismo , Masculino , Humanos , Ratones , Fibrosis , Modelos Animales de Enfermedad , Ácido Úrico/sangre , Transducción de Señal
2.
Appl Radiat Isot ; 214: 111555, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39423460

RESUMEN

Silicon carbide (SiC) detectors have excellent radiation detection capabilities for various radiation particles, including high energy resolution, fast response times, and good radiation resistance. A SiC radiation detection system was developed to measure the neutron fluence rate and the γ-ray dose rate in high intensity radiation fields. The system was composed of two SiC detectors, a temperature monitor, two preamplifiers for each SiC detector, a data acquisition unit with two signal channels, three pairs of communication devices, and an application software to analyze and visualize the measurement data. The two SiC detectors were fabricated based on two kinds of 4H-SiC diodes and used to respectively respond to neutrons and γ-rays. Repeated experiments showed that the two SiC detectors of the system can respond to α-particles, neutrons, and γ-rays. To verify the performance of the SiC detection system, including the response linearity of the neutron fluence rate, the measurement range of the γ-ray dose rate, and the radiation resistance of the SiC radiation detectors, the system was tested in multiple neutron and γ-ray fields. The tests results show the system can measure the neutron fluence rate from 5.64 × 10 2 cm-2 s-1 to 1.03 × 10 5 cm-2 s-1 with excellent linearity response, and the γ-ray dose rate from 0.005 Gy/h to 20 Gy/h. Furthermore, the SiC detectors demonstrated good radiation resistance. The neutron and γ-ray radiation field can still be measured stably by the system after exposure to neutron fluence of 1.07 × 10 14 cm-2 and γ-ray dose of 3.52 × 10 4 Gy. This work is the preliminary research to continue the exploration how to measure the n/γ hybrid fields accurately using SiC detectors considering the different energy of neutrons.

4.
Sci Rep ; 14(1): 25466, 2024 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-39461994

RESUMEN

Gas explosion is one of the five major hazards in mines, with about 36% of such incidents occurring in the excavation working face. Therefore, to investigate the impact of gas explosion propagation laws within excavation roadways, we conducted a simulation analysis of parameters such as peak of explosion overpressure, peak rate of pressure rise, and flame propagation speed in the presence of a Tunnel Boring Machine (TBM). In the presence of the TBM, the explosion overpressure approximately doubles, and the flame propagation speed also greatly increases, exacerbating the explosion hazard. Thus, when investigating gas explosion laws within excavation roadways, the presence of a TBM emerges as a significant factor that cannot be overlooked. Furthermore, an analysis of the effects of methane concentration and gas accumulation length on explosion parameters was conducted. The results indicate that when the flame passes through the TBM baffle, the average flame propagation speed increases the most when the methane concentration is 9.5%, increasing by about 6 times. In addition, as the gas accumulation length increases, both explosion overpressure and flame propagation speed gradually increase. Additionally, TBM has a certain impact on flame propagation and methane dissipation.

5.
Environ Pollut ; 362: 125007, 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39307337

RESUMEN

Microplastics (MPs) and antibiotics often coexist in complex marine environments, yet their combined detrimental effects on marine organisms remain underexplored. This study evaluated the effects of polyethylene microplastics (PE, 200 µg/L) and sulfamethoxazole (SMX, 50 µg/L), both individually and in combination, on Mytilus galloprovincialis. The exposure lasted 6 days, followed by a 6-day recovery period. Bioaccumulation, DNA damage, pollutants transport/metabolism related responses and responding alterations of mitogen-activated protein kinase (MAPK) signaling pathway were detected in gills and digestive glands. Bioaccumulation of SMX/PE in mussels occurred in a tissue-specific manner, co-exposure altered SMX contents in investigated tissues. Co-exposure did not induce extra DNA damage, elevated DNA damage was alleviated during the recovery period in all treated groups. The exposure of SMX/PE exerted different alterations in pollutants transport/metabolism related responses, characterized by multixenobiotic resistance and relative expression of key genes (cytochrome P450 monooxygenase, glutathione S-transferase, ATP-binding cassette transporters). Key molecules (p38 MAPK, c-jun N-terminal kinase, extracellular regulated protein kinase, nuclear factor-κB and tumor protein p53) in MAPK signaling pathway were activated at transcriptional and translational levels after SMX/PE and co-exposure. Co-regulation between MAPK members and pollutants transport/metabolism related factors was revealed, suggesting MAPK signaling pathway served as a regulating hub in exposed mussels to conquer SMX/PE stress. Overall, this study provides new insights on SMX/PE induced health risks in marine mussels and potential mechanism through MAPK cascades regulation.

6.
Artículo en Inglés | MEDLINE | ID: mdl-39317823

RESUMEN

Transesophageal echocardiography (TEE) is the standard method for diagnosing left atrial appendage (LAA) hypercoagulability in patients with atrial fibrillation (AF), which means LAA thrombus/sludge, dense spontaneous echo contrast and slow LAA blood flow velocity (< 0.25 m/s). Based on machine learning algorithms, cardiac computed tomography angiography (CCTA) radiomics features were adopted to construct prediction models and explore a suitable approach for diagnosing LAA hypercoagulability and adjusting anticoagulation. This study included 652 patients with non-valvular AF. The univariate analysis were used to select meaningful clinical characteristics to predict LAA hypercoagulability. Then 3D Slicer software was adopted to extract radiomics features from CCTA imaging. The radiomics score was calculated using the least absolute shrinkage and selection operator logistic regression analysis to predict LAA hypercoagulability. We then combined clinical characteristics and radiomics scores to construct a nomogram model. Finally, we got prediction models based on machine learning algorithms and logistic regression separately. The area under the receiver operating characteristic curve of radiomics score was 0.8449 in the training set and 0.7998 in the validation set. The nomogram model had a concordance index of 0.838. The final machine-learning based prediction models had good performances (best f1 score = 0.85). Radiomics features of long maximum diameter and high uniformity of Hounsfield unit in left atrial were significant predictors of the hypercoagulable state in LAA, with better predictive efficacy than clinical characteristics. Our combined models based on machine learning were reliable for hypercoagulable state screening and anticoagulation adjustment.

7.
Inorg Chem ; 63(40): 18531-18535, 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39311200

RESUMEN

In this study, we constructed a metal-binding site close to the heme cofactor in myoglobin (Mb) by covalently attaching a nonnative metal-binding ligand of bipyridine to Cys46 through the F46C mutation in the heme distal site. The X-ray structure of the designed enzyme, termed F46C-mBpy Mb, was solved in the Cu(II)-bound form, which revealed the formation of a heterodinuclear center of Cu-His-H2O-heme. Cu(II)-F46C-mBpy Mb exhibits not only nitrite reductase reactivity but also cascade reaction activity involving both hydrolysis and oxidation. Furthermore, F46C-mBpy Mb displays Mn-peroxidase activity by the oxidation of Mn2+ to Mn3+ using H2O2 as an oxidant. This study shows that the construction of a nonnative metal-binding site close to the heme cofactor is a convenient approach to creating an artificial metalloenzyme with a heterodinuclear center that confers multiple functions.


Asunto(s)
Hemo , Mioglobina , Mioglobina/química , Mioglobina/metabolismo , Hemo/química , Hemo/metabolismo , Sitios de Unión , Modelos Moleculares , Cobre/química , Cobre/metabolismo , Oxidación-Reducción , Metaloproteínas/química , Metaloproteínas/metabolismo , Cristalografía por Rayos X , Manganeso/química , Manganeso/metabolismo
8.
Int Immunopharmacol ; 142(Pt B): 113143, 2024 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-39306891

RESUMEN

Sarcopenia is a gradual and widespread decline in muscle mass and function in skeletal muscle, leading to significant implications for individuals and society. Currently, there is a lack of effective treatment methods for sarcopenia. Muscle satellite cells(SCs) play a crucial role in the occurrence and development of sarcopenia, and their proliferation and differentiation abilities are closely related to the progression of disease. This study evaluated the effects of exosomes derived from hypoxic preconditioning bone marrow mesenchymal stem cells (BMSCs) on the proliferation of SCs and skeletal muscle regeneration. We found that the capacity for the proliferation and differentiation of SCs in elderly rats was notably diminished, leading us to create a sarcopenia model in elderly rats. By separating and extracting exosomes from BMSCs treated with normoxic (N-Exos) and hypoxic (H-Exos) conditions, in vivo and in vitro studies showed that both N-Exos and H-Exos can regulate the proliferation and differentiation of SCs in elderly rats, and promote skeletal muscle regeneration and functional recovery. The beneficial effects of H-Exos were also more significant than those of the N-Exos group. In vitro studies demonstrated that H-Exos could influence the expression of the KLF7 gene and protein in SCs by delivering miR-210-3P. This, in turn, impacted the phosphorylation of the PI3K/AKT signaling pathway and contributed to the function of SCs. H-Exos stimulated SCs and promoted skeletal muscle regeneration during sarcopenia by delivering miR-210-3P to target the KLF7/PI3K/AKT signaling pathway. This may serve as a possible treatment option for sarcopenia.


Asunto(s)
Exosomas , Factores de Transcripción de Tipo Kruppel , Células Madre Mesenquimatosas , MicroARNs , Músculo Esquelético , Ratas Sprague-Dawley , Regeneración , Células Satélite del Músculo Esquelético , Animales , Exosomas/metabolismo , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Células Satélite del Músculo Esquelético/metabolismo , Células Satélite del Músculo Esquelético/fisiología , Factores de Transcripción de Tipo Kruppel/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Masculino , Ratas , Músculo Esquelético/fisiología , Músculo Esquelético/metabolismo , Proliferación Celular , Sarcopenia/terapia , Sarcopenia/metabolismo , Células Cultivadas , Diferenciación Celular , Transducción de Señal
9.
Chem Biodivers ; : e202401218, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39275987

RESUMEN

In this research, the essential oils (EOs) from different parts of Ocimum gratissimum var. suave were chemically characterized and evaluated for insecticidal activity, especially against two common storage pests of Chinese herbal medicines: Tribolium castaneum and Liposcelis bostrychophila. Ocimum gratissimum is a plant with several medicinal values in traditional Chinese medicine. In the study, EOs were successfully extracted from inflorescences (OGI) and stem-leaf (OGLS) parts of O. gratissimum by steam distillation and 16 compounds were identified by gas chromatography-mass spectrometry (GC-MS), of which eugenol was the major constituent in both extracts. In fumigation toxicity tests against both pests, the EOs showed limited toxicity against T. castaneum but showed better toxicity against L. bostrychophila. Contact toxicity tests showed that OGLS had better insecticidal potential than OGI, while the insecticidal effect of eugenol sometimes exceeded that of EOs. In addition, repellency experiments showed that O. gratissimum EOs repelled the pests to varying degrees, with the effect being influenced by concentration and exposure time. The results suggest that O. gratissimum EOs could be a promising alternative to synthetic insecticides for sustainable utilization.

10.
Chem Biodivers ; : e202400818, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39110524

RESUMEN

Insect infestations continually endanger stored goods, underscoring the significance of discovering eco-friendly insecticides for pest management. Essential oils (EOs) from different parts of Toddalia asiatica (leaf, fruit and branch) were extracted by hydrodistillation and analyzed by GC-MS. Carvene, p-cymene and muurolene are the principal compounds of T. asiatica leaf (TAL), T. asiatica fruit (TAF) and T. asiatica branch (TAB) EO respectively. Our work aimed to assess the contact toxicity and repellent effects of EOs on two storage pests, Tribolium castaneum and Lasioderma serricorne. All tested EOs exhibited obvious contact toxicity, especially, TAL EO against T. castaneum (33.48 µg/adult) and TAF EO against L. serricorne (16.42 µg/adult). Repellency tests revealed that TAL and TAF EOs, at a concentration of 78.63 nL/cm2, achieved nearing 100 % efficiency against T. castaneum. These results suggest that EOs of T. asiatica could be used as effective botanical insecticides for managing stored-product insects.

11.
Clin Transl Oncol ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39133386

RESUMEN

PPM1F has been shown to play diverse biological functions in the progression of multiple tumors. PPM1F controls the T788/T789 phosphorylation switch of ITGB1 and regulates integrin activity. However, the impacts of PPM1F and ITGB1 on ovarian cancer (OV) progression remain unclear. Whether there is such a regulatory relationship between PPM1F and ITGB1 in ovarian cancer has not been studied. Therefore, the purpose of this study is to elucidate the function and the mechanism of PPM1F in ovarian cancer. The expression level and the survival curve of PPM1F were analyzed by databases. Gain of function and loss of function were applied to explore the function of PPM1F in ovarian cancer. A tumor formation assay in nude mice showed that knockdown of PPM1F inhibited tumor formation. We tested the effect of PPM1F on ITGB1 dephosphorylation in ovarian cancer cells by co-immunoprecipitation and western blotting. Loss of function was applied to investigate the function of ITGB1 in ovarian cancer. ITGB1-mut overexpression promotes the progression of ovarian cancer. Rescue assays showed the promoting effect of ITGB1-wt on ovarian cancer is attenuated due to the dephosphorylation of ITGB1-wt by PPM1F. PPM1F and ITGB1 play an oncogene function in ovarian cancer. PPM1F regulates the phosphorylation of ITGB1, which affects the occurrence and development of ovarian cancer.

12.
J Agric Food Chem ; 72(36): 19852-19868, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39197065

RESUMEN

Alterations to the gut microbiota are associated with ulcerative colitis (UC), whereas restoration of normobiosis can effectively alleviate UC. l-Theanine has been shown to reshape the gut microbiota and regulate gut immunity. To investigate the mechanisms by which l-theanine alleviates UC, we used l-theanine and l-theanine fecal microbiota solution to treat UC mice. In this study, we used l-theanine and l-theanine fecal microbiota solution to treat UC mice to explore the mechanism by which l-theanine alleviates UC. By reducing inflammation in the colon, we demonstrated that l-theanine alleviates symptoms of UC. Meanwhile, l-theanine can improve the abundance of microbiota related to short-chain fatty acid, bile acid, and tryptophan production. Single-cell sequencing results indicated that l-theanine-mediated suppression of UC was associated with immune cell changes, especially regarding macrophages and T and B cells, and validated the immune cell responses to the gut microbiota. Further, flow cytometry results showed that the ability of dendritic cells, macrophages, and monocytes to present microbiota antigens to colonic T cells in an MHC-II-dependent manner was reduced after treating normal mouse fecal donors with l-theanine. These results demonstrate that l-theanine modulates colon adaptive and innate immunity by regulating the gut microbiota in an MHC-II-dependent manner, thereby alleviating UC.


Asunto(s)
Colitis Ulcerosa , Colon , Microbioma Gastrointestinal , Glutamatos , Ratones Endogámicos C57BL , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Glutamatos/farmacología , Glutamatos/administración & dosificación , Colitis Ulcerosa/inmunología , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/microbiología , Colon/inmunología , Colon/microbiología , Colon/efectos de los fármacos , Masculino , Humanos , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Antígenos de Histocompatibilidad Clase II/inmunología , Antígenos de Histocompatibilidad Clase II/genética , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/inmunología , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Heces/microbiología
13.
Carbohydr Polym ; 343: 122442, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39174123

RESUMEN

Nanocellulose, a versatile and sustainable nanomaterial derived from cellulose fibers, has attracted considerable attention in various fields due to its unique properties. Similar to dietary fibers, nanocellulose is difficult to digest in the human gastrointestinal tract. The indigestible nanocellulose is fermented by gut microbiota, producing metabolites and potentially exhibiting prebiotic activity in intestinal diseases. Additionally, nanocellulose can serve as a matrix material for probiotic protection and show promising prospects for probiotic delivery. In this review, we summarize the classification of nanocellulose, including cellulose nanocrystals (CNC), cellulose nanofibers (CNF), and bacterial nanocellulose (BNC), highlighting their distinct characteristics and applications. We discuss the metabolism-related characteristics of nanocellulose from oral ingestion to colon fermentation and introduce the prebiotic activity of nanocellulose in intestinal diseases. Furthermore, we provide an overview of commonly used nanocellulose-based encapsulation techniques, such as emulsification, extrusion, freeze drying, and spray drying, as well as the delivery systems employing nanocellulose matrix materials, including microcapsules, emulsions, and hydrogels. Finally, we discuss the challenges associated with nanocellulose metabolism, prebiotic functionality, encapsulation techniques, and delivery systems using nanocellulose matrix material for probiotics. This review will provide new insight into the application of nanocellulose in the treatment of intestinal diseases and probiotic delivery.


Asunto(s)
Celulosa , Microbioma Gastrointestinal , Nanopartículas , Probióticos , Celulosa/química , Celulosa/metabolismo , Humanos , Nanopartículas/química , Tracto Gastrointestinal/metabolismo , Tracto Gastrointestinal/microbiología , Animales , Nanofibras/química , Fermentación , Prebióticos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos
14.
Food Chem X ; 23: 101700, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39211763

RESUMEN

The clear juice fermentation technique for white wines suggests that white grape seeds, rich in flavan-3-ols and proanthocyanidins, are not effectively utilized in the winemaking process. This study incorporated 'Gewürztraminer' grape seeds into 'Cabernet Sauvignon' must before cold soak to investigate how the resultant red wines' phenolic compound profiles, color, and astringency were affected. The results showed that adding seeds primarily inhibited the leaching of flavan-3-ols from both skins and seeds. A significant increase in the levels of flavan-3-ols, tannins, and phenolic acids, as well as direct and aldehyde-bridged flavan-3-ol-anthocyanin polymers, were observed in the wines with additional seeds. This led to the improvement in the wine' red hue and its resistance to SO2 bleaching. Furthermore, the wine added with seeds exhibited stronger astringency compared to those without. The findings provide a promising winemaking strategy to improve color stability and intensify the astringency of red wines through the utilization of grape seeds.

15.
Artículo en Chino | MEDLINE | ID: mdl-39118505

RESUMEN

Objective:To observe the clinical effect of placing heterogeneous acellular dermal matrix membrane for laryngeal cavity wound healing after CO2 laser Type-Ⅴa cordectomy for glottic carcinoma. Methods:Thirty-five patients with bilateral vocal cord laryngeal cancer who underwent endoscopic CO2 laser surgery at the Department of Otorhinolaryngology Head and Neck Surgery, the Second Xiangya Hospital of Central South University from March 2018 to December 2019 were selected and divided into 2 groups, including 18 patients in the study group and 17 patients in the control group. The control group was simply placed silicone tube stent, while in the study group, heterogeneous acellular dermal matrix membrane was coated with silicone tube stent. The postoperative laryngeal wound repair and clinical manifestations were observed and compared between the two groups. Results:Compared postoperative laryngeal wound after 6 months: no patients in the study group had granulation tissue, whereas 4 patients in the control group had granulation tissue; 3 patients in the study group developed moderate to severe tissue adhesion, while 9 patients in the control group; 10 patients in the control group developed 2nd to 4th degree laryngeal obstruction, compared with only 4 patients in the study group. Conclusion:The primary placement of ADM can reduce laryngeal granulation tissue and tissue adhesion after CO2 laser Type-Ⅴa cordectomy for laryngeal cancer, and may reduce the occurrence of postoperative laryngeal obstruction.


Asunto(s)
Dermis Acelular , Neoplasias Laríngeas , Pliegues Vocales , Cicatrización de Heridas , Humanos , Masculino , Neoplasias Laríngeas/cirugía , Femenino , Persona de Mediana Edad , Pliegues Vocales/cirugía , Láseres de Gas/uso terapéutico , Endoscopía/métodos , Anciano
16.
Diabetol Metab Syndr ; 16(1): 193, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39118153

RESUMEN

BACKGROUND: The triglyceride-glucose (TyG) index is linked to both the development and progression of diabetes, while obesity remains a significant risk factor for this disease. However, the relationship between the TyG index and overweight or obese diabetes remains unclear. METHODS: This study was a cross-sectional analysis of data from 40,633 participants with body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were divided into groups of overweight or obese individuals with diabetes and those without diabetes according to the diabetes diagnostic criteria. The TyG index, the dependent variable, was determined using the equation ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. We explored the association between TyG index and diabetes in overweight or obese individuals through multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and analysis of threshold effects. RESULTS: Patients who were overweight or obese and had diabetes had higher TyG index levels than those without diabetes. After adjusting for confounders, our findings indicated a significant association between the TyG index and the risk of diabetes in overweight or obese individuals [odds ratio (OR) = 7.38, 95% confidence interval (CI): 6.98-7.81]. There was a J-shaped nonlinear association between TyG index and diabetes. When TyG index was > 4.46, the risk of diabetes increased sharply. Notably, a high baseline TyG index (Q4 group) correlated with a notably greater risk of diabetes than did the Q1 group, with an OR of 22.72 (95% CI: 20.52-25.16). Subgroup analysis revealed that the association between TyG and diabetes was stronger in females than in males (OR = 7.57, 95% CI: 6.76-8.48,), more significant in individuals with a BMI of 24-28 kg/m2 than in those with a BMI ≥ 28 kg/m2 (OR = 8.40, 95% CI: 7.83-9.02), and increased with age (OR = 8.15, 95% CI: 7.25-9.17) (all P for interaction < 0.001). CONCLUSION: Among overweight or obese individuals, a higher TyG index is associated with an elevated risk of diabetes, especially when TyG is > 4.46. Furthermore, factors such as sex, age, and BMI significantly influence the risk of diabetes in overweight or obese individuals. Specifically, older women with a BMI of 24-28 kg/m2 are at a greater risk of diabetes under similar TyG index conditions.

17.
Clin Exp Med ; 24(1): 195, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39167309

RESUMEN

OBJECTIVES: There is currently no evidence documenting the clinical characteristics and prognosis of non-high-risk patients with incidental stage T1 lung cancer (LC). The aim of this study was to investigate the clinical characteristics and prognosis of non-high-risk patients with incidental stage T1 LC. METHODS: This prospective cohort study included patients with incidental stage T1 LC who were diagnosed pathologically at the First Affiliated Hospital of Chongqing Medical University between 1st Jan 2019 and 31st Dec 2023. The follow-up time for all participants concluded on 31st Jan 2024, or upon death. All included patients were divided into non-high-risk (observation) and high-risk (control) groups based on the 2021 US preventative services task force recommendations. The primary outcomes were overall survival probability and LC-specific survival probability. The secondary outcomes were clinical characteristics, including demographic variables, histological types and TNM staging. RESULTS: We studied 1876 patients with incidental stage T1 LC. Of these, 1491 (79.48%) non-high-risk patients were included in the observation group, and the remaining 385 (20.52%) high-risk patients composed the control group. The follow-up interval was between 0 and 248 months for all participants, with a median time of 41.64 ± 23.85 months. The patients in the observation group were younger and had smaller tumors, more adenocarcinomas, and earlier disease stages than those in the control group (p ≤ 0.001). The overall survival probability (HR = 0.23, [95% CI: 0.18, 0.31], p < 0.001) and the LC-specific survival probability (HR = 0.23, [95% CI: 0.17, 0.31], p < 0.001) for the patients in the observation group were also both higher than those in the control group. The results appeared to be consistent across important subgroups. CONCLUSION: In this study, non-high-risk patients with incidental stage T1 LC were younger, had smaller tumors, had more adenocarcinomas, had a lower probability of metastasis, and had longer survival than did high-risk patients.


Asunto(s)
Neoplasias Pulmonares , Estadificación de Neoplasias , Humanos , Masculino , Femenino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Pronóstico , Hallazgos Incidentales , Análisis de Supervivencia , Adulto , Anciano de 80 o más Años , Factores de Riesgo
18.
PLoS Biol ; 22(8): e3002770, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39150946

RESUMEN

The development of multicellular organisms requires coordinated changes in gene expression that are often mediated by the interaction between transcription factors (TFs) and their corresponding cis-regulatory elements (CREs). During development and differentiation, the accessibility of CREs is dynamically modulated by the epigenome. How the epigenome, CREs, and TFs together exert control over cell fate commitment remains to be fully understood. In the Arabidopsis leaf epidermis, meristemoids undergo a series of stereotyped cell divisions, then switch fate to commit to stomatal differentiation. Newly created or reanalyzed scRNA-seq and ChIP-seq data confirm that stomatal development involves distinctive phases of transcriptional regulation and that differentially regulated genes are bound by the stomatal basic helix-loop-helix (bHLH) TFs. Targets of the bHLHs often reside in repressive chromatin before activation. MNase-seq evidence further suggests that the repressive state can be overcome and remodeled upon activation by specific stomatal bHLHs. We propose that chromatin remodeling is mediated through the recruitment of a set of physical interactors that we identified through proximity labeling-the ATPase-dependent chromatin remodeling SWI/SNF complex and the histone acetyltransferase HAC1. The bHLHs and chromatin remodelers localize to overlapping genomic regions in a hierarchical order. Furthermore, plants with stage-specific knockdown of the SWI/SNF components or HAC1 fail to activate specific bHLH targets and display stomatal development defects. Together, these data converge on a model for how stomatal TFs and epigenetic machinery cooperatively regulate transcription and chromatin remodeling during progressive fate specification.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Ensamble y Desensamble de Cromatina , Regulación de la Expresión Génica de las Plantas , Estomas de Plantas , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Estomas de Plantas/metabolismo , Estomas de Plantas/genética , Estomas de Plantas/crecimiento & desarrollo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Diferenciación Celular/genética , Cromatina/metabolismo
19.
Cardiovasc Diabetol ; 23(1): 226, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38951808

RESUMEN

BACKGROUND: The atherogenic index of plasma (AIP) is closely associated with the onset of diabetes, with obesity being a significant risk factor for type 2 diabetes mellitus (T2DM). However, the association between the AIP and T2DM in overweight and obese populations has been infrequently studied. Therefore, this study aimed to explore this association in overweight and obese individuals with T2DM. METHODS: This cross-sectional analysis utilized data from 40,633 participants with a body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were categorized into groups of overweight and obese individuals with and without diabetes according to the T2DM criteria. The AIP, our dependent variable, was calculated using the formula log10 [(TG mol/L)/HDL-C (mol/L)]. We investigated the association between the AIP and T2DM in overweight and obese individuals using multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and threshold effect analysis. Additionally, mediation analysis evaluated the role of inflammatory cells in AIP-related T2DM. RESULTS: Overweight and obese patients with T2DM exhibited higher AIP levels than those without diabetes. After adjusting for confounders, our results indicated a significant association between the AIP and the risk of T2DM in overweight and obese individuals (odds ratio (OR) = 5.17, 95% confidence interval (CI) 4.69-5.69). Notably, participants with a high baseline AIP (Q4 group) had a significantly greater risk of T2DM than those in the Q1 group, with an OR of 3.18 (95% CI 2.94-3.45). Subgroup analysis revealed that the association between the AIP and T2DM decreased with increasing age (interaction P < 0.001). In overweight and obese populations, the association between AIP and T2DM risk displayed a J-shaped nonlinear pattern, with AIP > - 0.07 indicating a significant increase in T2DM risk. Various inflammatory cells, including neutrophils, leukocytes, and monocytes, mediated 4.66%, 4.16%, and 1.93% of the associations, respectively. CONCLUSION: In overweight and obese individuals, the AIP was independently associated with T2DM, exhibiting a nonlinear association. Additionally, the association between the AIP and T2DM decreased with advancing age. Multiple types of inflammatory cells mediate this association.


Asunto(s)
Biomarcadores , Diabetes Mellitus Tipo 2 , Obesidad , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aterosclerosis/epidemiología , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Biomarcadores/sangre , Índice de Masa Corporal , China/epidemiología , HDL-Colesterol/sangre , Estudios Transversales , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Pueblos del Este de Asia , Obesidad/diagnóstico , Obesidad/sangre , Obesidad/epidemiología , Sobrepeso/epidemiología , Sobrepeso/sangre , Sobrepeso/diagnóstico , Sobrepeso/complicaciones , Pronóstico , Medición de Riesgo , Factores de Riesgo , Triglicéridos/sangre
20.
Genes Genomics ; 46(9): 1023-1036, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38997611

RESUMEN

BACKGROUND: Cold shock proteins (CSPs) are ubiquitous nucleic acid-binding proteins involved in growth, development, and stress response across various organisms. While extensively studied in many species, their regulatory roles in sweet cherry (Prunus avium L.) remain unclear. OBJECTIVE: To identify and analyze CSP genes (PavCSPs) in sweet cherry genome, and explore the differential responses of PavCSP1 and PavCSP3 to low temperature and salt stress. METHODS: Three methods were employed to identify and characterize CSP in sweet cherry genomes. To explore the potential functions and evolutionary relationships of sweet cherry CSP proteins, sequence alignment and phylogenetic tree incorporating genes from five species were conducted and constructed, respectively. To investigate the responses to abiotic stresses, cis-acting elements analysis and gene expression patterns to low-temperature and salt stress were examined. Moreover, transgenic yeasts overexpressing PavCSP1 or PavCSP3 were generated and their growth under stress conditions were observed. RESULTS: In this study, three CSP genes (PavCSPs) were identified and comprehensively analyzed. The quantitative real-time PCR revealed diverse expression patterns, with PavCSP1-3 demonstrating a particular activity in the upper stem and all members were responsive to low-temperature and salt stress. Further investigation demonstrated that transgenic yeasts overexpressing PavCSP1 or PavCSP3 exhibited improved growth states following high-salt and low-temperature stress. CONCLUSION: These findings elucidated the responses of PavCSP1 and PavCSP3 to salt and low-temperature stresses, laying the groundwork for further functional studies of PavCSPs in response to abiotic stresses.


Asunto(s)
Proteínas y Péptidos de Choque por Frío , Frío , Filogenia , Proteínas de Plantas , Prunus avium , Estrés Salino , Proteínas y Péptidos de Choque por Frío/genética , Proteínas y Péptidos de Choque por Frío/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Salino/genética , Prunus avium/genética , Prunus avium/metabolismo , Prunus avium/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Respuesta al Choque por Frío/genética , Genoma de Planta/genética
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