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1.
Biom J ; 66(5): e202300278, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38988195

RESUMEN

Rapid advances in high-throughput DNA sequencing technologies have enabled large-scale whole genome sequencing (WGS) studies. Before performing association analysis between phenotypes and genotypes, preprocessing and quality control (QC) of the raw sequence data need to be performed. Because many biostatisticians have not been working with WGS data so far, we first sketch Illumina's short-read sequencing technology. Second, we explain the general preprocessing pipeline for WGS studies. Third, we provide an overview of important QC metrics, which are applied to WGS data: on the raw data, after mapping and alignment, after variant calling, and after multisample variant calling. Fourth, we illustrate the QC with the data from the GENEtic SequencIng Study Hamburg-Davos (GENESIS-HD), a study involving more than 9000 human whole genomes. All samples were sequenced on an Illumina NovaSeq 6000 with an average coverage of 35× using a PCR-free protocol. For QC, one genome in a bottle (GIAB) trio was sequenced in four replicates, and one GIAB sample was successfully sequenced 70 times in different runs. Fifth, we provide empirical data on the compression of raw data using the DRAGEN original read archive (ORA). The most important quality metrics in the application were genetic similarity, sample cross-contamination, deviations from the expected Het/Hom ratio, relatedness, and coverage. The compression ratio of the raw files using DRAGEN ORA was 5.6:1, and compression time was linear by genome coverage. In summary, the preprocessing, joint calling, and QC of large WGS studies are feasible within a reasonable time, and efficient QC procedures are readily available.


Asunto(s)
Control de Calidad , Secuenciación Completa del Genoma , Humanos , Biometría/métodos , Bioestadística/métodos , Secuenciación de Nucleótidos de Alto Rendimiento
2.
Biomed Pharmacother ; 177: 117085, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38972150

RESUMEN

Accumulating evidence strongly support the key role of NLRP3-mediated pyroptosis in the pathogenesis and progression of vascular endothelial dysfunction associated with diabetes mellitus. Various studies have demonstrated that the activation or upregulation of Silent Information Regulation 2 homolog 2 (SIRT2) exerts inhibitory effect on the expression of NLRP3. Although 1,8-cineole has been found to protect against endothelial dysfunction and cardiovascular diseases, its role and mechanism in diabetic angiopathy remain unknown. Therefore, the aim of this study was to investigate the ameliorative effect of 1,8-cineole through SIRT2 on pyroptosis associated with diabetic angiopathy in human umbilical vein endothelial cells (HUVECs) and to elucidate the underlying mechanism. The findings revealed that 1,8-cineole exhibited a protective effect against vascular injury and ameliorated pathological alterations in the thoracic aorta of diabetic mice. Moreover, it effectively mitigated pyroptosis induced by palmitic acid-high glucose (PA-HG) in HUVECs. Treatment with 1,8-cineole effectively restored the reduced levels of SIRT2 and suppressed the elevated expression of pyroptosis-associated proteins. Additionally, our findings demonstrated the occurrence of NLRP3 deacetylation and the physical interaction between NLRP3 and SIRT2. The SIRT2 inhibitor AGK2 and siRNA-SIRT2 effectively attenuated the effect of 1,8-cineole on NLRP3 deacetylation in HUVECs and compromised its inhibitory effect against pyroptosis in HUVECs. However, overexpression of SIRT2 inhibited PA-HG-induced pyroptosis in HUVECs. 1,8-Cineole inhibited the deacetylation of NLRP3 by regulating SIRT2, thereby reducing pyroptosis in HUVECs. In conclusion, our findings suggest that PA-HG-induced pyroptosis in HUVECs plays a crucial role in the development of diabetic angiopathy, which can be mitigated by 1,8-cineole.


Asunto(s)
Diabetes Mellitus Experimental , Eucaliptol , Células Endoteliales de la Vena Umbilical Humana , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Sirtuina 2 , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis/efectos de los fármacos , Sirtuina 2/metabolismo , Sirtuina 2/antagonistas & inhibidores , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Eucaliptol/farmacología , Animales , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Angiopatías Diabéticas/tratamiento farmacológico , Angiopatías Diabéticas/metabolismo , Angiopatías Diabéticas/prevención & control , Angiopatías Diabéticas/patología
3.
Food Chem X ; 23: 101541, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-38974197

RESUMEN

The utilization of byproducts from foxtail millet polishing can reduce food loss and waste. Thus, it is necessary to know the chemical compounds from the millet and the segregation of the layers. The nutrients including minerals were compared among the husk, bran, and millet, and a LC-MS metabolomics analysis was also performed among them. The results showed that the protein, crude fat and 4 fatty acids, seven minerals, the nitrogen-containing compounds and phenolic acids were at much higher levels in the bran part than the husk and millet, whereas the husk only contained higher levels of dietary fibre, and some minerals. The millet section, as the edible part, contained the lowest level of chemical constituents. It illustrated that the bran part contained more functional and nutritional components than the millet and husk part. Therefore, the bran of the foxtail millet should be a food resources instead of wasting.

4.
Clin Nucl Med ; 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38861459

RESUMEN

ABSTRACT: As a common and highly aggressive malignancy of childhood, more than half of neuroblastomas are metastatic at the time of presentation. Herein, we reported 68Ga-FAPI-04 and 18F-FDG PET/CT findings in a 13-year-old girl with undifferentiated neuroblastoma. FAPI PET/CT showed intense uptake in the bone and bone marrow metastases. The primary lesions presented with low FAPI uptake but moderate FDG uptake. Above findings suggested the potential of FAPI PET/CT in the imaging evaluation of neuroblastoma.

5.
Food Chem ; 455: 139905, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38833870

RESUMEN

Pomegranate are often treated with preservatives during storage. This study investigated the effects of storage and food processing on the residual behavior of the five commonly used preservatives (prochloraz, thiophanate-methyl, pyrimethanil, imazalil, and difenoconazole) and their metabolites in pomegranate and its products. The LOQs for all target compounds were 0.001 mg kg-1. The residue levels of five preservatives in the calyx was highest, followed by the peel, stalk, septum, umbilicus, and seed. For the migration ability, the five preservatives from pomegranate peel to seed was negatively correlated with their octanol/water partition coefficients. The processing factors of each procedures of juice, wine, vinegar, and pectin processing were <1. Nevertheless, the PF values in drying peel during the overall process ranged from 1.26 to 4.09. Hence, it is worth noting that consumption of pomegranate essential oil and drying peel may pose a potential risk to the health of consumers.


Asunto(s)
Conservantes de Alimentos , Almacenamiento de Alimentos , Frutas , Granada (Fruta) , Granada (Fruta)/química , Granada (Fruta)/metabolismo , Conservantes de Alimentos/química , Conservantes de Alimentos/análisis , Conservantes de Alimentos/metabolismo , Frutas/química , Frutas/metabolismo , Manipulación de Alimentos
6.
Artículo en Inglés | MEDLINE | ID: mdl-38747223

RESUMEN

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative condition among the elderly population and the most common form of dementia, however, we lack potent interventions to arrest its inherent pathogenic vectors. Robust evidence indicates thermoregulatory perturbations during and before the onset of symptoms. Therefore, temperature-regulated biomarkers may offer clues to therapeutic targets during the presymptomatic stage. OBJECTIVE: The purpose of this study is to develop and assess a thermoregulation-related gene prediction model for Alzheimer's Disease diagnosis. METHOD: This study aims to utilize microarray bioinformatic analysis to identify the potential biomarkers of AD by analyzing four microarray datasets (GSE48350, GSE5281, GSE122063, and GSE181279) of AD patients. Furthermore, thermoregulation-associated hub genes were identified, and the expression patterns in the brain were explored. In addition, we explored the infiltration of immune cells with thermoregulation-related hub genes. Diagnostic marker validation was then performed at the single-cell level. Finally, the prediction of targeted drugs was performed based on the hub genes. RESULTS: Through the analysis of four datasets pertaining to AD, a total of five genes associated with temperature regulation were identified. Notably, CCK, CXCR4, SLC27A4, and SLC17A6 emerged as diagnostic markers indicative of AD-related brain injury. Furthermore, in the examination of peripheral blood samples from AD patients, SLC27A4 and CXCR4 were identified as pivotal diagnostic indicators. Regrettably, animal experimentation was not pursued to validate the data; rather, an assessment of temperature regulation-related genes was conducted. Future investigations will be undertaken to establish the correlation between these genes and AD pathology. CONCLUSION: Overall, CCK, CXCR4, SLC27A4, and SLC17A6 can be considered pivotal biomarkers for diagnosing the pathogenesis and molecular functions of AD.

7.
Chemosphere ; 359: 142309, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38735491

RESUMEN

Pesticides play vital roles in controlling pests and boosting crop yields. Imidacloprid is widely used all over the world and may form in agricultural products. The presence of pesticide residues in apples raises serious health concerns. Understanding the residual fate of imidacloprid is critical for food safety and human health. In this study, the dissipation behavior, metabolism, household processing and risk assessment of imidacloprid and its metabolites in apple were investigated from filed to products. Field experiment results suggested that the half-lives of imidacloprid at 5 times the recommended dosage was 1.5 times that of the standard dosage. And the final residues of imidacloprid were less than the established maximum residue limits (MRLs). Clarification and simmering had little effect on the reduction the residues of imidacloprid and its metabolites. The calculated processing factors were lower than 1 for imidacloprid and its metabolites, implying that the residual ratios of imidacloprid and its metabolites in each steps of the food processing were reduced. The risk quotients were <1 for all Chinese people, indicating that acceptable risks associated with dietary exposure to imidacloprid in apple. However, the higher risks were observed in young people than adults, and females faced higher risks than males. Given high residue levels in pomace, imidacloprid and its metabolites should be further studied in commercial byproducts.


Asunto(s)
Insecticidas , Malus , Neonicotinoides , Nitrocompuestos , Residuos de Plaguicidas , Malus/química , Malus/metabolismo , Neonicotinoides/metabolismo , Neonicotinoides/análisis , Nitrocompuestos/análisis , Nitrocompuestos/metabolismo , Medición de Riesgo , Residuos de Plaguicidas/análisis , Residuos de Plaguicidas/metabolismo , Insecticidas/análisis , Insecticidas/metabolismo , Humanos , Contaminación de Alimentos/análisis , Exposición Dietética/análisis , China , Femenino , Imidazoles/metabolismo , Imidazoles/análisis , Imidazoles/química
8.
Nucl Med Commun ; 45(8): 718-726, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38726632

RESUMEN

PURPOSE: The aim of this study was to evaluate metabolism change in reference organs (liver and mediastinum) and lymphoid cell-rich organs (spleen and bone marrow) during programmed cell death-1 immunotherapy in relapsed or refractory lymphoma patients. METHODS: A total of 66 patients with baseline and serial monitoring fluorodeoxyglucose (FDG) PET/computed tomography scans were retrospectively enrolled. Mean standardized uptake value (SUV) and maximum SUV of evaluated organs were obtained by two reviewers, and their association with tumor burden and clinical response were evaluated. Immune-related adverse events detected by FDG PET/computed tomography were also recorded. RESULTS: The SUV values of reference organs and lymphoid cell-rich organs did not change significantly during the immunotherapy process. The intersubject variability of these values ranged from 13.0 to 28.5%. Meanwhile, metabolism of reference organs was affected by neither the tumor burden nor clinical response. SUV change of lymphoid cell-rich organs was associated with clinical response to immunotherapy. Responders showed decreased metabolism, while nonresponders showed a reverse trend (spleen SUV max : -0.30 ±â€…0.47 vs. 0.18 ±â€…0.39, P  = 0.001, spleen SUV mean : -0.24 ±â€…0.39 vs. 0.14 ±â€…0.31, P  = 0.001; and bone marrow SUV max : -0.14 ±â€…0.37 vs. 0.07 ±â€…0.46, P  = 0.042, respectively). The influence of immune-related adverse events on the SUV change in evaluated organs was not significant. CONCLUSION: During programmed cell death-1 immunotherapy, metabolism change of reference organs is influenced neither by tumor burden nor by clinical response, while FDG uptake change of lymphoid cell-rich organs is significantly associated with clinical response.


Asunto(s)
Fluorodesoxiglucosa F18 , Inmunoterapia , Hígado , Linfoma , Mediastino , Tomografía Computarizada por Tomografía de Emisión de Positrones , Receptor de Muerte Celular Programada 1 , Humanos , Masculino , Femenino , Persona de Mediana Edad , Hígado/diagnóstico por imagen , Hígado/metabolismo , Linfoma/diagnóstico por imagen , Linfoma/terapia , Linfoma/metabolismo , Linfoma/inmunología , Anciano , Adulto , Receptor de Muerte Celular Programada 1/metabolismo , Estudios Retrospectivos , Transporte Biológico , Anciano de 80 o más Años , Linfocitos/metabolismo , Adulto Joven
9.
Hum Genet ; 143(5): 625-634, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38573379

RESUMEN

Large-scale association analyses using whole-genome sequence data have become feasible, but understanding the functional impacts of these associations remains challenging. Although many tools are available to predict the functional impacts of genetic variants, it is unclear which tool should be used in practice. This work provides a practical guide to assist in selecting appropriate tools for variant annotation. We conducted a MEDLINE search up to November 10, 2023, and included tools that are applicable to a broad range of phenotypes, can be used locally, and have been recently updated. Tools were categorized based on the types of variants they accept and the functional impacts they predict. Sequence Ontology terms were used for standardization. We identified 118 databases and software packages, encompassing 36 variant types and 161 functional impacts. Combining only three tools, namely SnpEff, FAVOR, and SparkINFERNO, allows predicting 99 (61%) distinct functional impacts. Thirty-seven tools predict 89 functional impacts that are not supported by any other tool, while 75 tools predict pathogenicity and can be used within the ACMG/AMP guidelines in a clinical context. We launched a website allowing researchers to select tools based on desired variants and impacts. In summary, more than 100 tools are already available to predict approximately 160 functional impacts. About 60% of the functional impacts can be predicted by the combination of three tools. Unexpectedly, recent tools do not predict more impacts than older ones. Future research should allow predicting the functionality of so far unsupported variant types, such as gene fusions.URL: https://cardio-care.shinyapps.io/VEP_Finder/ .Registration: OSF Registries on November 10, 2023, https://osf.io/s2gct .


Asunto(s)
Variación Genética , Programas Informáticos , Humanos , Biología Computacional/métodos , Bases de Datos Genéticas , Estudio de Asociación del Genoma Completo/métodos , Fenotipo
10.
Clin Nucl Med ; 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38598475

RESUMEN

ABSTRACT: A 17-year-old man presented with dull pain in the left upper abdomen for 1 month. Initial CT and gastroscopy revealed a mass in the gastric fundas, protruding into the lumen. Based on findings of a fine-needle biopsy, an inflammatory myofibroblastic tumor was suspected. Subsequent PET/CT showed increased FDG uptake in the gastric fundas as well as hepatogastric ligament, para-aortic region. Eventually, he underwent surgical resection, and histopathologic findings confirmed the diagnosis of splenosis.

12.
Asian J Pharm Sci ; 19(1): 100888, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38434719

RESUMEN

Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy, but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration. Herein, we designed a cancer-associated fibroblasts (CAFs) triggered structure-transformable nano-assembly (HSD-P@V), which can directionally deliver valsartan (Val, CAFs regulator) and doxorubicin (DOX, senescence inducer) to the specific targets. In detail, DOX is conjugated with hyaluronic acid (HA) via diselenide bonds (Se-Se) to form HSD micelles, while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer, which is coated on Val nanocrystals (VNs) surface for improving the stability and achieving responsive release. Once arriving at tumor microenvironment and touching CAFs, HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment. VNs can degrade the extracellular matrix, leading to the enhanced penetration of HSD. HSD targets tumor cells, releases DOX to induce senescence, and recruits effector immune cells. Furthermore, senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy. In vitro and in vivo results show that the nano-assembly remarkably inhibits tumor growth as well as lung metastasis, and extends tumor-bearing mice survival. This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.

13.
Sci Total Environ ; 922: 171228, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38402974

RESUMEN

UV-320 is classified as a Substance of Very High Concern (SVHC) by the European Chemicals Agency and has attracted significant attention due to its presence in the environment. Understanding the uptake, translocation and metabolic patterns of UV-320 in vegetables is essential for assessing their ability to bioaccumulate and potential risks to human health. In this study, we investigated the uptake and translocation of UV-320 in lettuce and radish by hydroponic experiments. The results showed that the root concentration factors (Croot/Csolution, RCF) of lettuce and radish were in the range of 47.9 to 464 mL/g and 194 to 787 mL/g, respectively. The transfer factors (Cshoot/Croot, TF) were observed to be 0.001-0.012 for lettuce and 0.02-0.05 for radish. Additionally, non-targeted screening identified twelve phase I and one phase II metabolites of UV-320 in vegetables, which were confirmed based on their molecular formulas and structures. The metabolic pathways involving oxidation, ketonylation and deamination were proposed in vegetables. Also, we have observed that UV-320 inhibits the growth of vegetables. Meanwhile, we evaluated the health risk of UV-320 in lettuce and radish and found that the consumption of lettuce is relatively safe, while the consumption of radish has a risk of HQ >1 for both adults and children, which should be seriously considered. This study provides valuable insights into the behavior and ecological risks of UV-320 in the environment.


Asunto(s)
Raphanus , Verduras , Adulto , Niño , Humanos , Verduras/química , Raíces de Plantas/metabolismo , Transporte Biológico , Oxidación-Reducción , Lactuca
14.
Eur J Radiol ; 172: 111353, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38320330

RESUMEN

PURPOSE: To systematically determine the role of FDG PET/CT for the diagnosis of bone marrow involvement in mature T- and natural killer (NK)-cell lymphomas. METHODS: The PubMed, Embase and Cochrane Library databases were searched to identify eligible studies. Data extraction and quality assessment were independently conducted. Then, pooled diagnostic performance with the 95 % confidence interval (CI) was calculated and further analyzed based on different interpretation criteria, tumor type and stage. RESULTS: Fifteen studies were eventually included for quantitative analysis. Overall, the methodological quality of included studies was acceptable. For detecting bone marrow involvement, FDG PET/CT achieved a poor sensitivity of 0.62 (95 % CI, 0.48-0.71) and a reasonable specificity of 0.92 (95 % CI, 0.87-0.96). Similar performance was observed for the specific type of extranodal NK/T-cell lymphoma (ENKTCL). In early-stage patients revealed by PET/CT, extremely small proportion (2/777) showed positive bone marrow biopsy, especially for the specific type of ENKTCL, whereas in advanced-stage patients, the specificity of FDG PET/CT dropped to 0.77 (95 % CI, 0.72-0.82). Regarding the interpretation, both diffuse and focal increased uptake patterns as positivity may result in increased sensitivity but decreased specificity compared with focal pattern alone as positivity. CONCLUSIONS: FDG PET/CT demonstrated excellent negative predictive value for detecting marrow involvement in early-stage patients with mature T- and NK-cell lymphomas, especially the ENKTCL. Conversely, FDG PET/CT showed poor performance for the diagnosis of bone marrow involvement in advanced-stage patients.


Asunto(s)
Linfoma , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Médula Ósea/diagnóstico por imagen , Médula Ósea/patología , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Rayos X , Tomografía de Emisión de Positrones , Biopsia , Linfoma/patología , Células Asesinas Naturales , Radiofármacos , Estudios Retrospectivos
15.
Clin Nucl Med ; 49(4): e191-e192, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38377365

RESUMEN

ABSTRACT: A 64-year-old man had progressive dysuria and nocturia for 1 month. Initial MRI and CT revealed localized thickening of the bladder wall with significant enhancement. Meanwhile, the lesion showed intense FDG accumulation on the delayed PET/CT. Taken together, a malignancy was suspected. However, the pathologic findings confirmed the diagnosis of eosinophilic cystitis.


Asunto(s)
Cistitis , Neoplasias , Masculino , Humanos , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones , Cistitis/diagnóstico por imagen
16.
Arch Biochem Biophys ; 751: 109847, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38052383

RESUMEN

Exposure to lipopolysaccharide (LPS) can lead to inflammation in a variety of tissues and organs. Selenium (Se) plays a crucial role in mitigating inflammatory damage. Compared with inorganic selenium, organic selenium, such as selenomethionine (SeMet), has the advantages of a higher absorption rate and lower toxicity in animals. This study examined the protective effects of SeMet on eggshell gland tissue damage caused by LPS. Hy-Line Brown laying hens were chosen as the experimental animals and were randomly assigned to four groups: control group (C), lipopolysaccharide group (LPS), SeMet group (Se), and SeMet + lipopolysaccharide group (Se + LPS). H&E staining and transmission electron microscope were performed to observe the pathological changes of eggshell glands, oxidative stress related indicators were measured using relevant kits, qRT‒PCR and western blotting were used to evaluate the mRNA and protein levels of the Nrf2 pathway, necroptosis, and inflammation related indicators. The results showed that LPS treatment increased the content of malondialdehyde (MDA), decreased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), and decreased the content of glutathione (GSH). LPS increased the levels of Keap1, RIPK1, RIPK3, MLKL, TNF-α, COX-2, and NF-κB, while decreasing the levels of HO-1, NQO1, Nrf2, and Caspase-8. However, SeMet treatment effectively reversed the changes of the above indicators, indicating that SeMet alleviates eggshell gland cell necroptosis-mediated inflammation induced by LPS via regulating the Keap1/Nrf2/HO-1 pathway. This study elucidated the mechanism by which SeMet alleviates LPS-induced eggshell gland tissue damage in Hy-Line Brown laying hens and provided a new direction for expanding the application of SeMet in the feeding and production of laying hens.


Asunto(s)
Selenio , Selenometionina , Femenino , Animales , Selenometionina/farmacología , Selenometionina/metabolismo , Lipopolisacáridos/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Pollos/metabolismo , Selenio/farmacología , Selenio/metabolismo , Cáscara de Huevo/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Necroptosis , Inflamación/metabolismo , Estrés Oxidativo , Glutatión/metabolismo , Antioxidantes/farmacología
17.
J Ethnopharmacol ; 321: 117550, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38065350

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Vascular endothelial cell senescence is associated with cardiovascular complications in diabetes. Essential oil from Fructus Alpiniae zerumbet (Pers.) B.L.Burtt & R.M.Sm. (EOFAZ) has potentially beneficial and promising diabetes-related vascular endothelial cell senescence-mitigating effects; however, the underlying molecular mechanisms remain unclear. AIM OF THE STUDY: To investigate the molecular effects of EOFAZ on vascular endothelial cell senescence in diabetes. MATERIALS AND METHODS: A diabetes mouse model was developed using a high-fat and high-glucose diet (HFD) combined with intraperitoneal injection of low-dose streptozotocin (STZ, 30 mg/kg) and oral treatment with EOFAZ. 4D label-free quantitative proteomics, network pharmacology, and molecular docking techniques were employed to explore the molecular mechanisms via which EOFAZ alleviates diabetes-related vascular endothelial cell senescence. A human aortic endothelial cells (HAECs) senescence model was developed using high palmitic acid and high glucose (PA/HG) concentrations in vitro. Western blotting, immunofluorescence, SA-ß-galactosidase staining, cell cycle, reactive oxygen species (ROS), cell migration, and enzyme linked immunosorbent assays were performed to determine the protective role of EOFAZ against vascular endothelial cell senescence in diabetes. Moreover, the PPAR-γ agonist rosiglitazone, inhibitor GW9662, and siRNA were used to verify the underlying mechanism by which EOFAZ combats vascular endothelial cell senescence in diabetes. RESULTS: EOFAZ treatment ameliorated abnormal lipid metabolism, vascular histopathological damage, and vascular endothelial aging in diabetic mice. Proteomics and network pharmacology analysis revealed that the differentially expressed proteins (DEPs) and drug-disease targets were associated with the peroxisome proliferator-activated receptor gamma (PPAR-γ) signalling pathway, a key player in vascular endothelial cell senescence. Molecular docking indicated that the small-molecule compounds in EOFAZ had a high affinity for the PPAR-γ protein. Western blotting and immunofluorescence analyses confirmed the significance of DEPs and the involvement of the PPAR-γ signalling pathway. In vitro, EOFAZ and rosiglitazone treatment reversed the effects of PA/HG on the number of senescent endothelial cells, expression of senescence-related proteins, the proportion of cells in the G0/G1 phase, ROS levels, cell migration rate, and expression of pro-inflammatory factors. The protective effects of EOFAZ against vascular endothelial cell senescence in diabetes were aborted following treatment with GW9662 or PPAR-γ siRNA. CONCLUSIONS: EOFAZ ameliorates vascular endothelial cell senescence in diabetes by activating PPAR-γ signalling. The results of the present study highlight the potential beneficial and promising therapeutic effects of EOFAZ and provide a basis for its clinical application in diabetes-related vascular endothelial cell senescence.


Asunto(s)
Diabetes Mellitus Experimental , Aceites Volátiles , Humanos , Ratones , Animales , Células Endoteliales , PPAR gamma/metabolismo , Rosiglitazona/metabolismo , Rosiglitazona/farmacología , Especies Reactivas de Oxígeno/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Aceites Volátiles/farmacología , Simulación del Acoplamiento Molecular , Farmacología en Red , Proteómica , ARN Interferente Pequeño , Glucosa/metabolismo
18.
Cytotherapy ; 26(1): 11-24, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37930294

RESUMEN

Mitochondrial DNA (mtDNA) is a critical genome contained within the mitochondria of eukaryotic cells, with many copies present in each mitochondrion. Mutations in mtDNA often are inherited and can lead to severe health problems, including various inherited diseases and premature aging. The lack of efficient repair mechanisms and the susceptibility of mtDNA to damage exacerbate the threat to human health. Heteroplasmy, the presence of different mtDNA genotypes within a single cell, increases the complexity of these diseases and requires an effective editing method for correction. Recently, gene-editing techniques, including programmable nucleases such as restriction endonuclease, zinc finger nuclease, transcription activator-like effector nuclease, clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated 9 and base editors, have provided new tools for editing mtDNA in mammalian cells. Base editors are particularly promising because of their high efficiency and precision in correcting mtDNA mutations. In this review, we discuss the application of these techniques in mitochondrial gene editing and their limitations. We also explore the potential of base editors for mtDNA modification and discuss the opportunities and challenges associated with their application in mitochondrial gene editing. In conclusion, this review highlights the advancements, limitations and opportunities in current mitochondrial gene-editing technologies and approaches. Our insights aim to stimulate the development of new editing strategies that can ultimately alleviate the adverse effects of mitochondrial hereditary diseases.


Asunto(s)
Edición Génica , Genes Mitocondriales , Animales , Humanos , Edición Génica/métodos , Mitocondrias/genética , ADN Mitocondrial/genética , Mutación , Mamíferos/genética
19.
Environ Sci Pollut Res Int ; 31(4): 6277-6287, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38147257

RESUMEN

Spirotetramat is widely used around the world to control sucking pests and may form in agricultural products. In the current study, the dissipation, residues, and evaluation of processing factor (PF) for spirotetramat and its formed metabolites were investigated during kiwifruit growing, storing, and processing. The residue analysis method was established based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with a QuEChERS method to detect the residues of spirotetramat and its metabolites in kiwifruit and its processed products. The method provided recoveries of 74.7-108.7%, and the relative standard deviations (RSDs) were 0.6-13.1%. The LOQs of spirotetramat and its four metabolites were 1 µg kg-1. The degradation of spirotetramat was best fitted for the first-order kinetics model with a half-life of 9.90-10.34 days in the field and 24.75-30.13 days during storage. Residues of spirotetramat and its formed metabolites in kiwifruit would not pose dietary risk to consumers. Moreover, the peeling and fermentation were the highest removal efficiency for the spirotetramat and its formed metabolite residues during processing. The PF values calculated after each individual process were < 1, indicating a significant reduction of residues in different processing processes of kiwifruit. The spirotetramat was degraded during kiwifruit wine-making process with half-lives of 3.36-4.91 days. B-enol and B-keto were the main metabolites detected in kiwifruit and its processed products. This study revealed the residues of spirotetramat and its formed metabolites in kiwifruit growing, storing, and processing, which helps provide reasonable data for studying the dietary risk factors of kiwifruits and products.


Asunto(s)
Compuestos Aza , Residuos de Plaguicidas , Compuestos de Espiro , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión , Compuestos Aza/química , Compuestos de Espiro/química , Residuos de Plaguicidas/análisis
20.
Clin Nucl Med ; 49(1): e38-e39, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37976526

RESUMEN

ABSTRACT: A 60-year-old man with colonic diffuse large B-cell lymphoma was referred for FDG PET/CT for initial staging. He was suspected of enterovesical fistula. After oral administration, large amounts of contrast agents accumulated in the bowel lumen and leaked into the bladder through a well-marked fistulous tract. Corresponding to the fistula, a linear pattern of FDG uptake extended from the bladder into the colonic lumen, and the measured SUV max inside the lesion was as high as that of the urinary bladder. Cystography confirmed the presence of the enterovesical fistula.


Asunto(s)
Fístula Intestinal , Linfoma , Fístula de la Vejiga Urinaria , Masculino , Humanos , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Medios de Contraste , Fístula Intestinal/complicaciones , Fístula Intestinal/diagnóstico por imagen
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