Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 433
Filtrar
3.
Anal Chem ; 96(16): 6321-6328, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38595097

RESUMO

Small extracellular vesicles (sEVs) are heterogeneous biological nanoparticles (NPs) with wide biomedicine applications. Tracking individual nanoscale sEVs can reveal information that conventional microscopic methods may lack, especially in cellular microenvironments. This usually requires biolabeling to identify single sEVs. Here, we developed a light scattering imaging method based on dark-field technology for label-free nanoparticle diffusion analysis (NDA). Compared with nanoparticle tracking analysis (NTA), our method was shown to determine the diffusion probabilities of a single NP. It was demonstrated that accurate size determination of NPs of 41 and 120 nm in diameter is achieved by purified Brownian motion (pBM), without or within the cell microenvironments. Our pBM method was also shown to obtain a consistent size estimation of the normal and cancerous plasma-derived sEVs without and within cell microenvironments, while cancerous plasma-derived sEVs are statistically smaller than normal ones. Moreover, we showed that the velocity and diffusion coefficient are key parameters for determining the diffusion types of the NPs and sEVs in a cancerous cell microenvironment. Our light scattering-based NDA and pBM methods can be used for size determination of NPs, even in cell microenvironments, and also provide a tool that may be used to analyze sEVs for many biomedical applications.


Assuntos
Vesículas Extracelulares , Vesículas Extracelulares/química , Humanos , Luz , Nanopartículas/química , Espalhamento de Radiação , Microambiente Celular , Tamanho da Partícula , Difusão , Microambiente Tumoral , Linhagem Celular Tumoral , Movimento (Física)
4.
Org Lett ; 26(15): 2939-2944, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38602425

RESUMO

A selective three-component 1,2-sulfonyl etherification of aryl 1,3-dienes enabled by copper catalysis to afford biologically interesting alkenyl 1,2-sulfone ether derivatives through C-S and C-O bond formation is described. The protocol proceeds with the sulfonyl chloride and alcohols under simple, mild, and base-free conditions, providing a straightforward route to sulfonylated allyl ether compounds with broad functional group tolerance and excellent chemo- and regioselectivity. Mechanistic studies indicate that the selective alkene difunctionalization includes a key copper-mediated single-electron transfer process.

5.
Endocrine ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564084

RESUMO

PURPOSE: The role of dual-specificity phosphatase-5 (DUSP5) in BRAF-mutant thyroid cancers remains unclear. The aims of this study are to investigate the role of DUSP5 in BRAF-mutant thyroid cancer cells, explore its value in the diagnosis and evaluate therapeutic potential of targeting DUSP5 combined with sorafenib for BRAF-mutant thyroid cancer patients. METHODS: The role of DUSP5 in thyroid cancer cells was determined by a series of in vitro and in vivo experiments. Underlying mechanisms were explored by western blotting analysis. The diagnostic value of combination detection of DUSP5 expression and BRAFV600E mutation was evaluated using ROC curve. RESULTS: Knocking down DUSP5 in BRAF-mutant thyroid cancer cells significantly inhibited colony formation, cell migration and invasion, meanwhile, induced cell cycle arrest and cell apoptosis. Moreover, inhibition of DUSP5 improved the anti-tumor efficacy of sorafenib both in vitro and in vivo. Besides, combination detection of DUSP5 expression and BRAFV600E mutation showed much more accuracy in preoperative diagnosis of thyroid cancer. CONCLUSIONS: Our data demonstrate an oncogenic role of DUSP5 in BRAF-mutant thyroid cancer cells, and combined analysis of its expression and BRAFV600E mutation can accurately diagnose thyroid cancer. In addition, inhibition of DUSP5 improves the response of BRAF-mutant thyroid cancer cells to sorafenib.

6.
Biomed Pharmacother ; 174: 116446, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38513599

RESUMO

Herein, we constructed innovative reduction-sensitive and targeted gelatin-based micelles for doxorubicin (DOX) delivery in tumor therapy. AS1411 aptamer-modified gelatin-ss-tocopherol succinate (AGSST) and the control GSST without AS1411 modification were synthesized and characterized. Antitumor drug DOX-containing AGSST (AGSST-D) and GSST-D nanoparticles were prepared, and their shapes were almost spherical. Reduction-responsive characteristics of DOX release in vitro were revealed in AGSST-D and GSST-D. Compared with non-targeted GSST-D, AGSST-D demonstrated better intracellular uptake and stronger cytotoxicity against nucleolin-overexpressed A549 cells. Importantly, AGSST-D micelles showed more effective killing activity in A549-bearing mice than GSST-D and DOX⋅HCl. It was revealed that AGSST-D micelles had no obvious systemic toxicity. Overall, AGSST micelles would have the potential to be an effective drug carrier for targeted tumor therapy.


Assuntos
Aptâmeros de Nucleotídeos , Doxorrubicina , Sistemas de Liberação de Medicamentos , Gelatina , Micelas , Oligodesoxirribonucleotídeos , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Animais , Humanos , Aptâmeros de Nucleotídeos/farmacologia , Gelatina/química , Células A549 , Sistemas de Liberação de Medicamentos/métodos , Camundongos , Oligodesoxirribonucleotídeos/administração & dosagem , Oligodesoxirribonucleotídeos/farmacologia , Camundongos Nus , Camundongos Endogâmicos BALB C , Portadores de Fármacos/química , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto , Liberação Controlada de Fármacos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo
7.
BMC Cancer ; 24(1): 385, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532312

RESUMO

Gliomas are the most common primary intracranial tumor worldwide. The maintenance of telomeres serves as an important biomarker of some subtypes of glioma. In order to investigate the biological role of RTEL1 in glioma. Relative telomere length (RTL) and RTEL1 mRNA was explored and regression analysis was performed to further examine the relationship of the RTL and the expression of RTEL1 with clinicopathological characteristics of glioma patients. We observed that high expression of RTEL1 is positively correlated with telomere length in glioma tissue, and serve as a poor prognostic factor in TERT wild-type patients. Further in vitro studies demonstrate that RTEL1 promoted proliferation, formation, migration and invasion ability of glioma cells. In addition, in vivo studies also revealed the oncogene role of RTEL1 in glioma. Further study using RNA sequence and phospho-specific antibody microarray assays identified JNK/ELK1 signaling was up-regulated by RTEL1 in glioma cells through ROS. In conclusion, our results suggested that RTEL1 promotes glioma tumorigenesis through JNK/ELK1 cascade and indicate that RTEL1 may be a prognostic biomarker in gliomas.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Glioma/patologia , Neoplasias Encefálicas/genética , Transformação Celular Neoplásica/genética , Oncogenes , Biomarcadores , Proliferação de Células , Proteínas Elk-1 do Domínio ets/genética , DNA Helicases/genética
8.
Int J Biol Macromol ; 265(Pt 1): 130709, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38462120

RESUMO

Versatile nanoplatform equipped with chemo-photodynamic therapeutic attributes play an important role in improving the effectiveness of tumor treatments. Herein, we developed multifunctional nanoparticles based on chondroitin sulfate A (CSA) for the targeted delivery of chlorin e6 (Ce6) and doxorubicin (DOX), in a combined chemo-photodynamic therapy against triple-negative breast cancer. CSA was chosen for its hydrophilic properties and its affinity to CD44 receptor-overexpressed tumor cells. The CSA-ss-Ce6 (CSSC) conjugate was synthesized utilizing a disulfide linker. Subsequently, DOX-loaded CSSC (CSSC-D) nanoparticles were fabricated, showcasing a nearly spherical shape with an average particle size of 267 nm. In the CSSC-D nanoparticles, the chemically attached Ce6 constituted 1.53 %, while the physically encapsulated DOX accounted for 8.11 %. Both CSSC-D and CSSC nanoparticles demonstrated a reduction-sensitive release of DOX or Ce6 in vitro. Under near-infrared (NIR) laser irradiation, CSSC-D showed the enhanced generation of reactive oxygen species (ROS), improving cytotoxic effects against triple-negative breast cancer 4T1 and MDA-MB-231 cells. Remarkably, the CSSC-D with NIR exhibited the most potent tumor growth inhibition in comparison to other groups in the 4T1-bearing Balb/c mice model. Overall, this CSSC-D nanoplatform shows significant promise as a powerful tool for a synergetic approach in chemo-photodynamic therapy in triple-negative breast cancer.


Assuntos
Nanopartículas , Fotoquimioterapia , Porfirinas , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Sulfatos de Condroitina , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Doxorrubicina/farmacologia , Doxorrubicina/química , Nanopartículas/química , Porfirinas/farmacologia , Porfirinas/química , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química
9.
Biomed Rep ; 20(5): 75, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38544959

RESUMO

The present study investigated the inhibitory and neuroprotective effects of Rubia yunnanensis alcohol extract (RY-A) on oxidative stress induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in HT22 cells. In vitro cultured HT22 cells were randomly divided into control, OGD/R, OGD/R + 100 µmol/l edaravone and OGD/R + 10, 20 and 40 µg/ml RY-A groups. Oxygen-sugar deprivation was performed with 10 mmol/l sodium dithionite combined with sugar-free DMEM medium for 2 h, followed by re-glycolization and reoxygenation for 2 h to establish an in vitro OGD/R model. Cell morphology was observed under a phase contrast microscope. Cell survival rate was detected by thiazolyl blue and lactate dehydrogenase and oxidative stress-related indexes were detected by commercial kits. The effects and metabolic alterations of RY-A treatment after OGD/R were evaluated using ultra-high performance liquid chromatography and mass spectrometry. Protein levels were further examined by western blotting. The results showed that cells in the OGD/R group were swollen and lacked protrusions, had significantly reduced viability and had significantly elevated oxidative stress-related indexes of reactive oxygen species, nitric oxide levels and malondialdehyde content and significantly reduced activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase, compared with controls. Compared with the OGD/R group, the RY-A group had significantly improved cell morphology and significantly increased cell viability and in terms of oxidative stress, exhibited significantly reduced reactive oxygen species, nitric oxide levels and malondialdehyde content, as well as significantly increased superoxide dismutase and glutathione peroxidase activities. Metabolomic analysis identified changes in 20 metabolites, including L-tryptophan, ornithine, eicosapentaenoic acid-d5, isosafrole and xanthine. Metabolomics analysis showed that the pathways affected included those related to phenylalanine, tyrosine and tryptophan biosynthesis, the prolactin signaling pathway and amphetamine addiction. These results suggested that RY-A had significant preventive effects on an in vitro model of cerebral ischemia-reperfusion injury simulated by OGD/R and the mechanism may be related to increased tryptophan content, activation of indoleamine 2,3-dioxygenase enzymes and inhibition of oxidative stress.

10.
Horm Metab Res ; 56(5): 368-372, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38447949

RESUMO

The aim of the study was to investigate the iodine intake in the resident population in Xi'an and analyze the relationship between iodine nutritional status and the prevalence of subclinical hypothyroidism and thyroid nodules (TNs). A total of 2507 people were enrolled in Xi'an. Venous serum thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), urinary iodine concentration (UIC), and thyroid ultrasonography were collected. Patients with abnormal TSH were checked for free thyroxine (FT4) and triiodothyronine (FT3). Adults in Xi'an had median UICs of 220.80 µg/L and 178.56 µg/l, respectively. A sum of 16.78% of people had subclinical hypothyroidism. Both iodine excess and iodine deficit increased the frequency of subclinical hypothyroidism. The lowest was around 15.09% in females with urine iodine levels between 200 and 299 µg/l. With a rate of 10.69%, the lowest prevalence range for males was 100-199 µg/l. In Xi'an, 11.37% of people have TNs. In comparison to other UIC categories, TN occurrences were higher in females (18.5%) and males (12%) when UIC were below 100 µg/l. In conclusion, iodine intake was sufficient in the Xi'an area, while the adults' UIC remains slightly higher than the criteria. Iodine excess or deficiency can lead to an increase in the prevalence of subclinical hypothyroidism. Patients with iodine deficiency are more likely to develop TNs.


Assuntos
Hipotireoidismo , Iodo , Nódulo da Glândula Tireoide , Humanos , Iodo/urina , Iodo/sangue , Feminino , Masculino , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/urina , Nódulo da Glândula Tireoide/sangue , Hipotireoidismo/epidemiologia , Hipotireoidismo/urina , Hipotireoidismo/sangue , Prevalência , Adulto , Pessoa de Meia-Idade , Idoso
11.
Pharmacol Res ; 202: 107113, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38387744

RESUMO

Sepsis, a complex clinical syndrome characterized by an exaggerated host response to infection, often necessitates hospitalization and intensive care unit admission. Delayed or inaccurate diagnosis of sepsis, coupled with suboptimal treatment strategies, can result in unfavorable outcomes, including mortality. Maresins, a newly discovered family of lipid mediators synthesized from docosahexaenoic acid by macrophages, have emerged as key players in promoting inflammation resolution and the termination of inflammatory processes. Extensive evidence has unequivocally demonstrated the beneficial effects of maresins in modulating the inflammatory response associated with sepsis; however, their bioactivity and functions exhibit remarkable diversity and complexity. This article presents a comprehensive review of recent research on the role of maresins in sepsis, aiming to enhance our understanding of their effectiveness and elucidate the specific mechanisms underlying their actions in sepsis treatment. Furthermore, emerging insights into the management of patients with sepsis are also highlighted.


Assuntos
Anti-Inflamatórios , Sepse , Humanos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/complicações , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácidos Docosa-Hexaenoicos/farmacologia , Eicosanoides , Mediadores da Inflamação , Sepse/tratamento farmacológico , Sepse/complicações
12.
Chem Commun (Camb) ; 60(20): 2716-2731, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38353179

RESUMO

Real-time monitoring of biocatalytic-based processes is significantly improved and simplified when they can be visualized. Visual monitoring can be achieved by integrating a fluorescent unit with the biocatalyst. Herein, we outline the design strategies of fluorescent probes for monitoring biocatalysis: (1) probes for monitoring biocatalytic transfer: γ-glutamine is linked to the fluorophore as both a recognition group and for intramolecular charge transfer (ICT) inhibition; the probe is initially in an off state and is activated via the transfer of the γ-glutamine group and the release of the free amino group, which results in restoration of the "Donor-π-Acceptor" (D-π-A) system and fluorescence recovery. (2) Probes for monitoring biocatalytic oxidation: a propylamine is connected to the fluorophore as a recognition group, which cages the hydroxyl group, leading to the inhibition of ICT; propylamine is oxidized and subsequently ß-elimination occurs, resulting in exposure of the hydroxyl group and fluorescence recovery. (3) Probes for monitoring biocatalytic reduction: a nitro group attached to a fluorophore as a fluorescence quenching group, this is converted to an amino group by catalytic reduction, resulting in fluorescence recovery. (4) Probes for monitoring biocatalytic hydrolysis: ß-D-galactopyranoside or phosphate acts as a recognition group attached to hydroxyl groups of the fluorophore; the subsequent biocatalytic hydrolysis reaction releases the hydroxyl group resulting in fluorescence recovery. Following these 4 mechanisms, fluorophores including cyanine, coumarin, rhodamine, and Nile-red, have been used to develop systems for monitoring biocatalytic reactions. We anticipate that these strategies will result in systems able to rapidly diagnose and facilitate the treatment of serious diseases.


Assuntos
Corantes Fluorescentes , Glutamina , Biocatálise , Rodaminas , Propilaminas
13.
Angew Chem Int Ed Engl ; 63(15): e202400459, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38317310

RESUMO

We realized the microenvironment-differential Imaging of demethylated metabolites of methionine and the regional regulation of ferroptosis.


Assuntos
Ferroptose , Metionina , Fluorescência , Racemetionina , Diagnóstico por Imagem , Microambiente Tumoral
14.
Front Endocrinol (Lausanne) ; 15: 1292412, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38344659

RESUMO

Context: Diabetic retinopathy (DR) and diabetic nephropathy (DN), are major microvascular complications of diabetes. DR is an important predictor of DN, but the relationship between the severity of DR and the pathological severity of diabetic glomerulopathy remains unclear. Objective: To investigate the relationship between severity of diabetic retinopathy (DR) and histological changes and clinical indicators of diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). Methods: Patients with T2DM (n=272) who underwent a renal biopsy were eligible. Severity of DR was classified as non-diabetic retinopathy, non-proliferative retinopathy, and proliferative retinopathy (PDR). Relationship between DN and DR and the diagnostic efficacy of DR for DN were explored. Results: DN had a higher prevalence of DR (86.4%) and DR was more severe. The sensitivity and specificity of DR in DN were 86.4% and 78.8%, while PDR was 26.4% and 98.5%, respectively. In DN patients, the severity of glomerular lesions (p=0.001) and prevalence of KW nodules (p<0.001) significantly increased with increasing severity of DR. The presence of KW nodules, lower hemoglobin levels, and younger age were independent risk factors associated with more severe DR in patients with DN. Conclusion: DR was a good predictor of DN. In DN patients, the severity of DR was associated with glomerular injury, and presence of KW nodules, lower hemoglobin levels and younger age were independent risk factors associated with more severe DR. Trial registration: ClinicalTrails.gov, NCT03865914.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Retinopatia Diabética , Humanos , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/etiologia , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Retinopatia Diabética/diagnóstico , Fatores de Risco , Hemoglobinas
15.
J Autoimmun ; 144: 103176, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38364575

RESUMO

Psoriasis, a chronic inflammatory skin condition, is often accompanied by psychiatric comorbidities such as anxiety, depression, suicidal ideation, and other mental disorders. Psychological disorders may also play a role in the development and progression of psoriasis. The intricate interplay between the skin diseases and the psychiatric comorbidities is mediated by the 'skin-brain axis'. Understanding the mechanisms underlying psoriasis and psychiatric comorbidities can help improve the efficacy of treatment by breaking the vicious cycle of diseases. T cells and related cytokines play a key role in the pathogenesis of psoriasis and psychiatric diseases, and are crucial components of the 'skin-brain axis'. Apart from damaging the blood-brain barrier (BBB) directly, T cells and secreted cytokines could interact with the hypothalamic-pituitary-adrenal axis (HPA axis) and the sympathetic nervous system (SNS) to exacerbate skin diseases or mental disorders. However, few reviews have systematically summarized the roles and mechanisms of T cells in the interaction between psoriasis and psychiatric comorbidities. In this review, we discussed several key T cells and their roles in the 'skin-brain axis', with a focus on the mechanisms underlying the interplay between psoriasis and mental commodities, to provide data that might help develop effective strategies for the treatment of both psoriasis and psychiatric comorbidities.


Assuntos
Sistema Hipotálamo-Hipofisário , Psoríase , Humanos , Linfócitos T , Sistema Hipófise-Suprarrenal , Psoríase/epidemiologia , Citocinas
16.
Cancer ; 130(10): 1884-1893, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38236717

RESUMO

BACKGROUND: The presence of circulating plasma cells (CPCs) is an important laboratory indicator for the diagnosis, staging, risk stratification, and progression monitoring of multiple myeloma (MM). Early detection of CPCs in the peripheral blood (PB) followed by timely interventions can significantly improve MM prognosis and delay its progression. Although the conventional cell morphology examination remains the predominant method for CPC detection because of accessibility, its sensitivity and reproducibility are limited by technician expertise and cell quantity constraints. This study aims to develop an artificial intelligence (AI)-based automated system for a more sensitive and efficient CPC morphology detection. METHODS: A total of 137 bone marrow smears and 72 PB smears from patients with at Zhongshan Hospital, Fudan University, were retrospectively reviewed. Using an AI-powered digital pathology platform, Morphogo, 305,019 cell images were collected for training. Morphogo's efficacy in CPC detection was evaluated with additional 184 PB smears (94 from patients with MM and 90 from those with other hematological malignancies) and compared with manual microscopy. RESULTS: Morphogo achieved 99.64% accuracy, 89.03% sensitivity, and 99.68% specificity in classifying CPCs. At a 0.60 threshold, Morphogo achieved a sensitivity of 96.15%, which was approximately twice that of manual microscopy, with a specificity of 78.03%. Patients with CPCs detected by AI scanning had a significantly shorter median progression-free survival compared with those without CPC detection (18 months vs. 34 months, p< .01). CONCLUSIONS: Morphogo is a highly sensitive system for the automated detection of CPCs, with potential applications in initial screening, prognosis prediction, and posttreatment monitoring for MM patients. PLAIN LANGUAGE SUMMARY: Diagnosing and monitoring multiple myeloma (MM), a type of blood cancer, requires identifying and quantifying specific cells called circulating plasma cells (CPCs) in the blood. The conventional method for detecting CPCs is manual microscopic examination, which is time-consuming and lacks sensitivity. This study introduces a highly sensitive CPC detection method using an artificial intelligence-based system, Morphogo. It demonstrated remarkable sensitivity and accuracy, surpassing conventional microscopy. This advanced approach suggests that early and accurate CPC detection is achievable by morphology examination, making efficient CPC screening more accessible for patients with MM. This innovative system has the potential to be used in the diagnosis and risk assessment of MM.


Assuntos
Aprendizado Profundo , Mieloma Múltiplo , Plasmócitos , Humanos , Mieloma Múltiplo/patologia , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Plasmócitos/patologia , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Células Neoplásicas Circulantes/patologia , Prognóstico , Adulto
17.
Biomed Rep ; 20(2): 19, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38170026

RESUMO

Atherosclerosis is a multifactorial vascular disease caused by endothelial dysfunction. Because of adverse reactions to drugs used to treat atherosclerosis. For example, statins, which significantly reduce the burden of atherosclerotic disease, have been associated with muscle toxicity. There is a need to identify novel drugs for the prevention and treatment of atherosclerosis Rubia yunnanensis is a herbs commonly used in Asian countries for its protective effects against cardiovascular diseases. However, the mechanism of action of R. yunnanensis extract in carotid artery atherosclerosis has not been found. The carotid artery is usually used as a site for clinical evaluation of atherosclerosis. The present study aimed to determine the mechanism of action of R. yunnanensis extract in the inhibition of carotid atherosclerosis in apolipoprotein E gene knockout (ApoE-/-) mice. The mechanism of atherosclerosis inhibition was elucidated by detecting the blood lipid level, carotid artery pathology, and the protein expression of PI3K and AKT. The present study demonstrated that ethanol extract of R. yunnanensis reduced lipid levels, intima damage and carotid lipid accumulation and increased p-PI3K/PI3K and p-AKT/AKT protein levels in ApoE-/- mice fed high-fat diet for 12 weeks. It was hypothesized that the effects of R. yunnanensis extract may be achieved by regulation of the phosphatidylinositol-3-kinase/protein kinase B signaling pathway. Ethanol extract of R. yunnanensis decreased carotid atherosclerosis in ApoE-/- mice fed a high-fat diet via the phosphatidylinositol-3-kinase/protein kinase B signaling pathway. Therefore, R. yunnanensis may be a promising option for treating atherosclerosis in the future.

18.
Exp Clin Endocrinol Diabetes ; 132(1): 17-22, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38237612

RESUMO

OBJECTIVE: Antithyroid drug (ATD)-induced agranulocytosis (TIA) is the most serious adverse effect during ATD treatment of Graves' disease (GD). Previously, the MICA gene was reported to be associated with TIA. MICA protein is an important ligand for the NKG2D protein, which is encoded by the KLRK1 gene and KLRC4-KLRK1 read-through transcription. This study further investigated the association between KLRC4-KLRK1 gene polymorphisms and susceptibility to TIA. METHODS: Twenty-eight candidate single nucleotide polymorphisms (SNPs) on KLRC4-KLRK1 read-through transcription were evaluated by the iPLEX MassARRAY system in 209 GD control patients and 38 TIA cases. RESULTS: A significant association of rs2734565 polymorphism with TIA was found (p=0.02, OR=1.80, 95% CI=1.09-2.96). The haplotype C-A-A-C-G, including rs2734565-C, was associated with a significantly higher risk of TIA (p=4.79E-09, OR=8.361, 95% CI=3.737-18.707). In addition, the interval time from hyperthyroidism to agranulocytosis onset was shorter in patients carrying the rs2734565-C allele than in non-carrying groups (45.00 (14.00-6570.00) d vs. 1080.00 (30.00-3600.00) d, p=0.046), and the interval from ATD treatment to agranulocytosis onset was also shorter in patients carrying rs2734565-C allele (29.00 (13.00-75.00) d vs. 57.50 (21.00-240.00) d, p=0.023). CONCLUSIONS: The findings suggest that the KLRC4-KLRK1 gene polymorphism is associated with susceptibility and progression of ATD-induced agranulocytosis. Patients carrying the rs2734565-C allele had a higher susceptibility and faster onset time of TIA.


Assuntos
Agranulocitose , Doença de Graves , Hipertireoidismo , Humanos , Agranulocitose/induzido quimicamente , Agranulocitose/genética , Agranulocitose/tratamento farmacológico , Antitireóideos/efeitos adversos , Doença de Graves/tratamento farmacológico , Doença de Graves/genética , Hipertireoidismo/tratamento farmacológico , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília K de Receptores Semelhantes a Lectina de Células NK/uso terapêutico , Polimorfismo de Nucleotídeo Único
19.
J Magn Reson Imaging ; 59(5): 1593-1602, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37610209

RESUMO

BACKGROUND: Identification of non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus (T2DM) may help tailor treatment. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is a promising tool to evaluate renal function but its potential role in the clinical differentiation between diabetic nephropathy (DN) and NDRD remains unclear. PURPOSE: To investigate the added role of IVIM-DWI in the differential diagnosis between DN and NDRD in patients with T2DM. STUDY TYPE: Prospective. POPULATION: Sixty-three patients with T2DM (ages: 22-69 years, 17 females) confirmed by renal biopsy divided into two subgroups (28 DN and 35 NDRD). FIELD STRENGTH/SEQUENCE: 3 T/ T2 weighted imaging (T2WI), and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). ASSESSMENT: The parameters derived from IVIM-DWI (true diffusion coefficient [D], pseudo-diffusion coefficient [D*], and pseudo-diffusion fraction [f]) were calculated for the cortex and medulla, respectively. The clinical indexes related to renal function (eg cystatin C, etc.) and diabetes (eg diabetic retinopathy [DR], fasting blood glucose, etc.) were measured and calculated within 1 week before MRI scanning. The clinical model based on clinical indexes and the IVIM-based model based on IVIM parameters and clinical indexes were established and evaluated, respectively. STATISTICAL TESTS: Student's t-test; Mann-Whitney U test; Fisher's exact test; Chi-squared test; Intraclass correlation coefficient; Receiver operating characteristic analysis; Hosmer-Lemeshow test; DeLong's test. P < 0.05 was considered statistically significant. RESULTS: The cortex D*, DR, and cystatin C values were identified as independent predictors of NDRD in multivariable analysis. The IVIM-based model, comprising DR, cystatin C, and cortex D*, significantly outperformed the clinical model containing only DR, and cystatin C (AUC = 0.934, 0.845, respectively). DATA CONCLUSION: The IVIM parameters, especially the renal cortex D* value, might serve as novel indicators in the differential diagnosis between DN and NDRD in patients with T2DM. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Nefropatias Diabéticas/diagnóstico por imagem , Cistatina C , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Estudos Prospectivos , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Movimento (Física)
20.
Luminescence ; 39(1): e4600, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37752625

RESUMO

Hypochlorite (ClO- ), as a kind of essential reactive oxygen species, plays a crucial role in vitro and in vivo. Here, a ratiometric fluorescent probe (TPAM) was designed and constructed for sensing ClO- based on substituted triphenylamine and malononitrile, which exhibited obvious colour transfer from orange to colourless under daylight accompanied by noticeable fluorescence change from red to green in response to ClO- . TPAM could effectively monitor ClO- with the merits of fast response, excellent selectivity, high sensitivity and a low detection limit of 0.1014 µM. 1 H NMR, mass spectra and theoretical calculations proved that ClO- caused the oxidation of the carbon-carbon double bond in TPAM, resulting in compound 1 and marked changes in colour and fluorescence. In addition, TPAM was utilized for imaging ClO- in living cells successfully with good photostability and biocompatibility.


Assuntos
Corantes Fluorescentes , Ácido Hipocloroso , Corantes Fluorescentes/química , Espectrometria de Fluorescência , Imagem Óptica , Carbono
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...