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1.
Sci Rep ; 14(1): 18547, 2024 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-39122810

RESUMO

Observational studies have shown that non-alcoholic fatty liver disease (NAFLD) is strongly associated with metabolic dysfunction. However, there is a paucity of research on whether changes in indicators of serum metabolism contribute to the development of NAFLD. This study was conducted with 4084 participants who underwent healthy physical examinations at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China, in 2022 and 2023. Baseline and follow-up measurements, including anthropometric data, abdominal ultrasound and blood samples were collected. The diagnosis of NAFLD was based on the 2010 Chinese Guidelines on Diagnosis and Treatment of NAFLD. Multiple logistic regression was utilized to analyze the odds ratios (ORs) for the 1-year risk of NAFLD in connection with both baseline metabolic indicators and changes in metabolic indicators observed over the course of 1 year. A total of 3425 study participants who were free of NAFLD at baseline, including 1146 men and 2279 women, were included in the final analysis. The mean age was 34.43 ± 7.20 years. Participants who developed NAFLD were older, male and had higher levels of body mass index (BMI), blood pressure, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), free triiodothyronine (fT3), uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and lower levels of high-density lipoprotein cholesterol (HDL-C) and free thyroxine (fT4) (all P values < 0.05). The multivariable model showed that baseline BMI, diastolic blood pressure (DBP), TG, TC, HDL-C, LDL-C, UA, fT4, fT3, ALT and changes in TG, HDL-C, and UA were associated with the 1-year risk of developing NAFLD. The risk of NAFLD increased by 56% [OR 1.56, 95% Confidence Interval (CI) 1.32-1.87] and 40% (OR 1.40, 95% CI 1.19-1.64) for each standard deviation (SD) increase in altered TG values (1.01 mmol/L) and altered UA values (55 µmol/L) respectively. Conversely, for each SD (0.27 mmol/L) increase in HDL-C change, the 1-year risk of incident NAFLD was reduced by 50% (OR 0.50, 95% CI 0.40-0.62). The present study suggested that increases in TG and UA, and decreases in HDL-C, significantly increase the risk of developing NAFLD. Therefore, more attention should be paid to these factors in the management and prevention of NAFLD.


Assuntos
Lipídeos , Hepatopatia Gordurosa não Alcoólica , Ácido Úrico , Humanos , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Masculino , Feminino , Ácido Úrico/sangue , Adulto , China/epidemiologia , Lipídeos/sangue , Pessoa de Meia-Idade , Fatores de Risco , Incidência , Índice de Massa Corporal
2.
Food Chem Toxicol ; 192: 114915, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39127121

RESUMO

There is a lack of information regarding the presence of heavy metals in feed ingredients for animals. Therefore, this study examines 10 feed samples collected from commercial pet food in South African market. The optimal working parameters for ultrasound assisted hydrogen peroxide extraction (UA-HPE) confirmed by multivariate optimization were sonication temperature at 80 °C for 60 min, sample mass of 0.1 g, and H2O2 concentration of 5 mol/L. The UA-HPE results demonstrated high accuracy of (>95%), reproducibility (≤1.9%), low method of detection limits (0.3498 and 0.49 µg/g), and strong linearity as confirmed by regression analysis. The environmental friendliness of the UA-HPE method was assessed using AGREEPrep metric tool that resulted with a score of 0.74. The concentration levels of Cd, Pb and As, ranged between 0.86 and 11.34, 4.50-11.45, and 2.61-12.5 µg/g, respectively greater than the standardized limits, whilst Cr, and Sn were below the limits of detection in all pet food. The health index calculations (HI > 1) revealed that the cat, dog, and horse feed pose health risk for animal consumption. Consequently, this study demonstrated a green, efficient, and cost-effective method for the analysis of animal feed with high accuracy.

3.
Cardiovasc Diagn Ther ; 14(3): 328-339, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975002

RESUMO

Background: Both early detection and treatment for acute coronary syndrome (ACS) have positively affected prognosis. A microRNA, miRNA-21 (miR-21), may have additional diagnostic potential for ACS among the others. This systematic review and meta-analysis aimed to evaluate the potential role of miR-21 in identifying ACS. Methods: PubMed, EMBASE and CENTRAL databases were searched up to March 17, 2024, for case-control and cohort studies assessing the diagnostic value of circulating miR-21 in patients with ACS. The search was limited to studies published in either English or Chinese. The primary outcome was the discriminative ability to circulate miR-21 for ACS, represented by the area under the standard receiver operating characteristic curve (AUC) analysis. Meta-analyses combined the AUCs using a random-effects model. Heterogeneity among the studies was detected by the I2 and Q statistics. The quality of the studies included was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Publication bias analysis was assessed constructing by the Egger's test (PROSPERO: CRD42020209424). Results: Eleven case-control studies containing a total of 2,413 subjects with 1,236 ACS cases and 1,177 controls were included. The mean age of participants in these studies ranges between 51.0 and 69.0 years. The meta-analysis showed an overall pooled AUC of 0.779 [95% confidence interval (CI): 0.715-0.843], with high heterogeneity noted between the studies (Q statistic =190.64, I2=94.23%, P<0.001). In subgroup analyses according to the subtypes of ACS, a pooled AUC of 0.767 (95% CI: 0.648-0.887) was derived from the studies focused on acute myocardial infarction cases only. The pooled AUC for unstable angina was 0.770 (95% CI: 0.718-0.822). In subgroup analyses according to the types of control groups, pooled AUC for ACS versus healthy controls was 0.779 (95% CI: 0.715-0.843), whereas the pooled AUC for ACS versus unhealthy controls was 0.740 (95% CI: 0.645-0.836). The quality assessment showed that the studies' overall quality was moderate. No evidence of publication bias was noted (P=0.49). Conclusions: Circulating miR-21 shows abilities to differentiate between ACS and non-ACS, suggesting its potential as a novel diagnostic biomarker for ACS. However, the evidence is weakened by high heterogeneity observed among the studies. Further research is essential before it can be applied in clinical practice.

4.
Transl Androl Urol ; 13(6): 1024-1036, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38983473

RESUMO

Background: Urine testing as a routine screening programme, abnormal test results can be suggestive to clinicians but can sometimes be overlooked, and the establishment of a diagnostic model can better assist clinicians in identifying potential problems. BLD (blood), LEU (leukocyte), PRO (protein) and GLU (glucose) are the four most important parameters in urine testing, and the accuracy of their results is a key concern for clinicians, so it is essential to verify the accuracy of their results. In this study, we evaluated the analytical and clinical performance of Mindray's automatic urine dry chemistry analyzer, the UA-5600 (Hereinafter referred to as the (UA-5600), and the test strips configured with the instrument, and developed a machine-learning (ML) model for kidney disease screening from the results of 11 parameters output from the UA-5600 with the aim of detecting abnormal urine test results. Methods: Urine samples from outpatients and inpatients at The First Affiliated Hospital of Sun Yat-sen University were collected from August to September 2022 to evaluate the performance of the Mindray UA-5600 dry chemistry analyzer and test strips. The evaluation of the UA-5600 and its test strips focused on the agreement of the urine BLD and LEU readings with the RBC (red blood cell) and WBC (white blood cell) counts obtained by the Mindray EH-2090 urine formed element analyzer. We also compared the PRO and GLU readings with the results of the Mindray BS-2800M biochemistry analyzer. Urine samples from outpatients and inpatients were retrospectively analysed and grouped according to LIS diagnosis. Additionally, eight ML models for kidney disease screening were developed using 11 parameters measured by the UA-5600. And the model was validated by the validation set. Results: The UA-5600 had an 89.55% concordance rate for BLD and a 91.04% concordance rate for LEU compared to the EH-2090 analyzer. When benchmarked against the BS-2800M, the concordance rates for PRO and GLU were 94.14% and 95.20%, respectively. A total of 1,691 samples were used for the construction of the ML models, of which 346 patients (135 males and 211 females, age range: 18 to 98 years) diagnosed with renal disease, and 1,345 patients (397 males and 948 females, age range: 18 to 92 years) with non-renal disease diagnosed with other conditions. Notably, the Naïve Bayes (NB) model, which was built from the UA-5600 parameters, demonstrated superior predictive capabilities for renal disease, with an area under the receiver operating characteristic curve of 0.9470, a sensitivity of 0.7767, and a specificity of 0.9457. Conclusions: The Mindray UA-5600 demonstrates robust detection abilities for both BLD and LEU, and its results for PRO and GLU align closely with those obtained from the chemistry analyzer. The NB model has a good screening ability and shows promise as an effective screening tool.

5.
Int J Biol Sci ; 20(9): 3317-3333, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38993555

RESUMO

The glomerular podocyte, a terminally differentiated cell, is crucial for the integrity of the glomerular filtration barrier. The re-entry of podocytes into the mitotic phase results in injuries or death, known as mitotic catastrophe (MC), which significantly contributes to the progression of diabetic nephropathy (DN). Furthermore, P62-mediated autophagic flux has been shown to regulate DN-induced podocyte injury. Although previous studies, including ours, have demonstrated that ursolic acid (UA) mitigates podocyte injury by enhancing autophagy under high glucose conditions, the protective functions and potential regulatory mechanisms of UA against DN have not been fully elucidated. For aiming to investigate the regulatory mechanism of podocyte injuries in DN progression, and the protective function of UA treatment against DN progression, we utilized db/db mice and high glucose (HG)-induced podocyte models in vivo and in vitro, with or without UA administration. Our findings indicate that UA treatment reduced DN progression by improving biochemical indices. P62 accumulation led to Murine Double Minute gene 2 (MDM2)-regulated MC in podocytes during DN, which was ameliorated by UA through enhanced P62-mediated autophagy. Additionally, the overexpression of NF-κB p65 or TNF-α abolished the protective effects of UA both in vivo and in vitro. Overall, our results provide strong evidence that UA could be a potential therapeutic agent for DN, regulated by inhibiting podocyte MC through the NF-κB/MDM2/Notch1 pathway by targeting autophagic-P62 accumulation.


Assuntos
Autofagia , Nefropatias Diabéticas , Podócitos , Triterpenos , Ácido Ursólico , Podócitos/efeitos dos fármacos , Podócitos/metabolismo , Animais , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Camundongos , Autofagia/efeitos dos fármacos , Mitose/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL
6.
Risk Anal ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862413

RESUMO

Investigating the effects of spatial scales on the uncertainty and sensitivity analysis of the social vulnerability index (SoVI) model output is critical, especially for spatial scales finer than the census block group or census block. This study applied the intelligent dasymetric mapping approach to spatially disaggregate the census tract scale SoVI model into a 300-m grids resolution SoVI map in Davidson County, Nashville. Then, uncertainty analysis and variance-based global sensitivity analysis were conducted on two scales of SoVI models: (a) census tract scale; (b) 300-m grids scale. Uncertainty analysis results indicate that the SoVI model has better confidence in identifying places with a higher socially vulnerable status, no matter the spatial scales in which the SoVI is constructed. However, the spatial scale of SoVI does affect the sensitivity analysis results. The sensitivity analysis suggests that for census tract scale SoVI, the indicator transformation and weighting scheme are the two major uncertainty contributors in the SoVI index modeling stages. While for finer spatial scales like the 300-m grid's resolution, the weighting scheme becomes the uttermost dominant uncertainty contributor, absorbing uncertainty contributions from indicator transformation.

7.
Oncol Rep ; 52(1)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38847277

RESUMO

Ursolic acid (UA), a pentacyclic triterpenoid that has been found in a broad variety of fruits, spices and medicinal plants, has various biological effects such as reducing inflammation, protecting cells from damage, and preserving brain function. However, its impact on ferroptosis in cancer stem­like cells remains unexplored. The present study investigated the effect of UA on MDA­MB­231 and BT­549 cell­derived triple­negative breast CSCs (BCSCs) and its potential ferroptosis pathway. The effects of ferroptosis on BCSCs were demonstrated by the detection of ferroptosis­related indexes including the intracellular level of glutathione, malondialdehyde, reactive oxygen species and iron. The effects of UA on the biological behaviors of BCSCs were analyzed by Cell Counting Kit­8, stemness indexes detection and mammosphere formation assay. The mechanism of UA induction on BCSCs was explored by reverse transcription­quantitative PCR and western blotting. BALB/c­nude mice were subcutaneously injected with MDA­MB­231­derived BCSCs to establish xenograft models to detect the effects of UA in vivo. The results revealed that BCSCs have abnormal iron metabolism and are less susceptible to ferroptosis. UA effectively reduces the stemness traits and proliferation of BCSCs in spheroids and mice models by promoting ferroptosis. It was observed that UA stabilizes Kelch­like ECH­associated protein 1 and suppresses nuclear factor erythroid­related factor 2 (NRF2) activation. These findings suggested that the ability of UA to trigger ferroptosis through the inhibition of the NRF2 pathway could be a promising approach for treating BCSCs, potentially addressing metastasis and drug resistance in triple­negative breast cancer (TNBC). This expands the clinical applications of UA and provides a theoretical basis for its use in TNBC treatment.


Assuntos
Proliferação de Células , Ferroptose , Fator 2 Relacionado a NF-E2 , Células-Tronco Neoplásicas , Neoplasias de Mama Triplo Negativas , Triterpenos , Ácido Ursólico , Ensaios Antitumorais Modelo de Xenoenxerto , Ferroptose/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Triterpenos/farmacologia , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Camundongos , Feminino , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
8.
Cell Biochem Funct ; 42(4): e4074, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38874340

RESUMO

Usnic acid (UA) is a unique bioactive substance in lichen with potential anticancer properties. Recently, we have reported that UA can reduce 7,12-dimethylbenz[a] anthracene-induced oral carcinogenesis by inhibiting oxidative stress, inflammation, and cell proliferation in a male golden Syrian hamster in vivo model. The present study aims to explore the relevant mechanism of cell death induced by UA on human oral carcinoma (KB) cell line in an in vitro model. We found that UA can induce apoptosis (cell death) in KB cells by decreasing cell viability, increasing the production of reactive oxygen species (ROS), depolarizing mitochondrial membrane potential (MMP) levels, causing nuclear fragmentation, altering apoptotic morphology, and causing excessive DNA damage. Additionally, UA inhibits the expression of Bcl-2, a protein that promotes cell survival, while increasing the expression of p53, Bax, Cytochrome-c, Caspase-9, and 3 proteins in KB cells. UA also inhibits the expression of nuclear factor-κB (NF-κB), a protein that mediates the activation of pro-inflammatory cytokines such as TNF-α and IL-6, in KB cells. Furthermore, UA promotes apoptosis by enhancing the mitochondrial-mediated apoptotic mechanism through oxidative stress, depletion of cellular antioxidants, and an inflammatory response. Ultimately, the findings of this study suggest that UA may have potential as an anticancer therapeutic agent for oral cancer treatments.


Assuntos
Apoptose , Benzofuranos , Inflamação , Neoplasias Bucais , NF-kappa B , Transdução de Sinais , Humanos , Apoptose/efeitos dos fármacos , NF-kappa B/metabolismo , Benzofuranos/farmacologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Neoplasias Bucais/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Sobrevivência Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos
9.
J Biol Chem ; 300(8): 107485, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906255

RESUMO

Hyperuricemia (HUA) is a metabolic disorder characterized by elevated serum uric acid (UA), primarily attributed to the hepatic overproduction and renal underexcretion of UA. Despite the elucidation of molecular pathways associated with this underexcretion, the etiology of HUA remains largely unknown. In our study, using by Uox knockout rats, HUA mouse, and cell line models, we discovered that the increased WWC1 levels were associated with decreased renal UA excretion. Additionally, using knockdown and overexpression approaches, we found that WWC1 inhibited UA excretion in renal tubular epithelial cells. Mechanistically, WWC1 activated the Hippo pathway, leading to phosphorylation and subsequent degradation of the downstream transcription factor YAP1, thereby impairing the ABCG2 and OAT3 expression through transcriptional regulation. Consequently, this reduction led to a decrease in UA excretion in renal tubular epithelial cells. In conclusion, our study has elucidated the role of upregulated WWC1 in renal tubular epithelial cells inhibiting the excretion of UA in the kidneys and causing HUA.

10.
Talanta ; 277: 126236, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38795590

RESUMO

The dyeing and adulteration of traditional Chinese medicines (TCMs) are continuously updated. Valuable analytical methods for the daily inspection of illegal colorant additives in TCMs and the preparations are in demand. Two deep eutectic solvent (DES)-based vortex-assisted liquid-liquid microextraction (VA-LLME) and ultrasonic-assisted solid-liquid microextraction (UA-SLME) were developed for the sample pretreatment of ten water-soluble colorants and five water-insoluble colorants, respectively, followed by an HPLC-DAD detection. Fifteen colorants were analyzed at four detection wavelengths within 40 min of gradient elution. The optimal DES of VA-LLME and UA-SLME were screened from 23 homemade DESs. The factors affecting the extraction efficiency of VA-LLME and UA-SLME were optimized systematically. Under the optimal conditions, ten water-soluble colorants analyzed by DES-based VA-LLME-HPLC-DAD showed good linearity (R ≥ 0.9995) within the optimal linear range. The LODs and LOQs were 0.2-1.0 µg g-1 and 0. 5-5.0 µg g-1, respectively. The recoveries of spiked samples were 80.2%-104.7 %, with RSDs ≤ 4.39 %. Five water-insoluble colorants of Sudan I‒IV and Sudan 7B analyzed by DES-based UA-SLME-HPLC-DAD showed good linearity (R ≥ 0.9995) within the optimal linear range. The LODs and LOQs were 0.8-8.0 µg g-1 and 4.0-40.0 µg g-1, respectively. The recoveries of spiked samples were 94.2%-103.1 %, with RSDs ≤ 4.81 %. The proposed DES-based VA-LLME-HPLC-DAD was successfully applied to analyze six water-soluble yellow colorants in Cuscutae Semen, salted Cuscutae Semen, and four water-soluble red colorants in Schisandrae Chinensis Fructus. The proposed DES-based UA-SLME-HPLC-DAD was successfully applied to analyze five water-insoluble red colorants in Dieda pills. The study provides analytical method options for routine tests of water-soluble, water-insoluble, or both water-soluble/-insoluble illegal colorant additives in herbal medical materials and preparations by the relevant proposed DES-based sample pretreatment method or a combination of the two proposed DES-based methods.


Assuntos
Corantes , Medicamentos de Ervas Chinesas , Interações Hidrofóbicas e Hidrofílicas , Microextração em Fase Líquida , Cromatografia Líquida de Alta Pressão/métodos , Microextração em Fase Líquida/métodos , Corantes/química , Corantes/análise , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Medicina Tradicional Chinesa , Solventes/química
11.
Sensors (Basel) ; 24(7)2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38610283

RESUMO

This article presents the hardware and software architectures used to implement the Modbus Extension (ModbusE) IIoT gateway, the performance of the acquisition cycle at the PRU real-time programmable core level, the acquisition cycle communication flow-dispatcher-OPC UA server (Linux)-OPC UA client (Windows) as well as the performance analysis of data communications between the IIoT ModbusE gateway and the OPC UA client (Windows). In order to be able to implement both the ModbusE acquisition cycle and the OPC UA server, the BeagleBone Black Board was chosen as the hardware platform. This board uses the Sitara AM335x processor (Texas Instruments (TI), Dallas, TX, USA) from Texas Instruments. Thus, the acquisition cycle was implemented on the PRU0 real-time core, and the OPC UA server, running under the Linux operating system, was implemented on the ARM Cortex A8 processor. From the analysis of the communication speed of the messages between the OPC UA client and the ModbusE servers, it was found that the ModbusE acquisition cycle speed was higher than the acquisition speed of the OPC UA client.

12.
Mikrochim Acta ; 191(5): 243, 2024 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-38575711

RESUMO

PEDOT: PSS has been used as a biomimetic uric acid (UA) sensor but suffers from unfortunate low detection limit (LOD), narrow detection range and poor stability. Herein, we get graphdiyne (GDY) marry PEDOT:PSS to create a very stable GDY@PEDOT:PSS heterostructure for a biomimetic UA sensor, which accomplishes the lowest LOD (6 nM), the widest detection range (0.03 µM-7 mM) and the longest stability (98.1% for 35 days) among the related UA sensors. The sensor was successfully used to in situ real-time detection of  UA in sweat. The enhancement mechanisms of the sensor were investigated, and results discover that C≡C of GDY and C = C of PEDOT:PSS can cross-link each other by π-π interactions, making not only the former strongly resistant against oxidation deterioration, but also causes the latter to efficiently prevent water swelling of polymer for poor conductivity, thereby leading to high stability from both components. While the stabilized heterostructure can also offer more active sites by enhanced absorption of UA via π-π interactions for highly sensitive detection of UA. This work holds great promise for a practical sweat UA sensor while providing scientific insight to design a stable and electrocatalytically active structure from two unstable components.


Assuntos
Grafite , Suor , Ácido Úrico , Limite de Detecção
13.
Angew Chem Int Ed Engl ; 63(29): e202405494, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38661015

RESUMO

Polynuclear metal hydride clusters play important roles in various catalytic processes, with most of the reported polynuclear metal hydride clusters adopting a polyhedral three-dimensional structure. Herein, we report the first example of a planar tetranuclear uranium hydride cluster [(CpCMe2CMe2Cp)U]4(µ2-H)4(µ3-H)4 (U4H8). It was synthesized by reacting an ansa-bis(cyclopentadienyl) ligand-supported uranium chloride precursor [(CpCMe2CMe2Cp)U]3(µ2-Cl)3(µ3-Cl)2 with NaHBEt3. The presence of hydrides in U4H8 was confirmed by NMR spectroscopy and its reactivity with phenol and carbon tetrachloride. DFT calculations also facilitated the determination of the hydrides' positions in U4H8, featuring four bridging µ2-H ligands and four face-capping µ3-H ligands, with the four U centers arranged in a rhombic geometry. The U4H8 represents not only the first example of planar polynuclear actinide metal hydride cluster but also the uranium hydride cluster with the highest nuclearity reported to date.

14.
Adv Sci (Weinh) ; 11(18): e2310065, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38447147

RESUMO

According to the latest evidence, the microbial metabolite Urolithin A (UA), known for its role in promoting cellular health, modulates CD8+ T cell-mediated antitumor activity. However, the direct target protein of UA and its underlying mechanism remains unclear. Here, this research identifies ERK1/2 as the specific target crucial for UA-mediated CD8+ T cell activation. Even at low doses, UA markedly enhances the persistence and effector functions of primary CD8+ cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells both in vitro and in vivo. Mechanistically, UA interacts directly with ERK1/2 kinases, enhancing their activation and subsequently facilitating T cell activation by engaging ULK1. The UA-ERK1/2-ULK1 axis promotes autophagic flux in CD8+ CTLs, enhancing cellular metabolism and maintaining reactive oxygen species (ROS) levels, as evidenced by increased oxygen consumption and extracellular acidification rates. UA-treated CD8+ CTLs also display elevated ATP levels and enhanced spare respiratory capacity. Overall, UA activates ERK1/2, inducing autophagy and metabolic adaptation, showcasing its potential in tumor immunotherapy and interventions for diseases involving ERKs.


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia , Linfócitos T CD8-Positivos , Cumarínicos , Animais , Humanos , Camundongos , Autofagia/imunologia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/efeitos dos fármacos , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Cumarínicos/farmacologia , Cumarínicos/metabolismo , Modelos Animais de Doenças , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/imunologia , Camundongos Endogâmicos C57BL , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/metabolismo
15.
Sci Rep ; 14(1): 5923, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467667

RESUMO

Uric acid (UA) is associated with non-alcoholic fatty liver disease (NAFLD). However, it is unclear whether UA plays a predictive role in NAFLD prognosis. This study aimed to explore the relationship between UA levels and mortality in NAFLD patients without severe renal disease. Data were obtained from the Third National Health and Nutrition Examination Survey (NHANES). Time-dependent Cox regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for mortality. Overall, 2493 individuals with NAFLD and estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 were included in this study. The median follow-up period was 26.58 years. Patients were divided into high and low-UA groups according to UA levels. Time-independent Cox regression showed that UA level was not an independent risk factor for mortality in NAFLD patients without decreased eGFR (P > 0.05). After matching for age and sex using the propensity score matching method, UA remained not independently associated with death in NAFLD patients (P > 0.05). Similar results were found for cardiovascular-related and cancer-related deaths. Although UA is closely related to NAFLD, UA levels are not independently associated with the long-term survival of patients with NAFLD without decreased eGFR.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Ácido Úrico , Inquéritos Nutricionais , Prognóstico , Fatores de Risco
16.
BMC Pregnancy Childbirth ; 24(1): 160, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395789

RESUMO

BACKGROUND: Elevated maternal serum uric acid (UA) levels were associated with adverse perinatal outcomes. This study aimed to examine the association between UA and the risk of low birth weight (LBW) / small for gestational age (SGA). METHODS: A cohort study of women delivered in Shanghai maternity hospital was included between 2017 and 2021. Electronic medical records were utilized to extract information and antenatal care records. The cut-off value of UA was 360 µmol/L. The outcome was LBW/SGA, with LBW defined as birth weight below 2500 g and SGA indicating birth weight below the 10th percentile of average weight for gestational age. The assessment of SGA was based on the Chinese standard curve for birth weight at various gestational ages. Univariate, multivariate logistic regression models, restricted cubic spline were used in this study, with adjustments made for confounding factors. RESULTS: Sixty-nine thousand six hundred seventy-four live births and singleton pregnancies were included. The ratio of LBW/SGA was 3.3%/9%. Maternal UA levels were significantly negatively correlated with birth weight. High UA levels were associated with high risk of LBW/SGA, especially in third trimester. In BMI < 25 group, the risk of LBW increased to 2.35-fold (95%CI, 1.66-3.31) in hyperuricemic group (UA > 360 µmol/L). The SGA risk was 1.66-fold (95%CI, 1.37-2.00). Gestational hypertension (GH) with hyperuricemica increased the risk of LBW (aOR = 4.00, 95%CI, 2.01-7.93) and SGA (aOR = 2.63, 95%CI, 1.83-3.78). Preeclampsia (PE) with hyperuricemia increased the risk of LBW (aOR = 1.38, 95%CI, 0.63-3.03) and SGA (aOR = 1.81, 95%CI, 1.18-2.78). In delivery gestational week (DGW) ≥ 37 group, if UA > 360 µmol/L, the incidence of LBW increased to 2.46-fold (95%CI, 1.62, 3.73) and the incidence of SGA increased to 1.52-fold (95%CI, 1.24, 1.87). In DGW < 37 group, if UA > 360 µmol/L, the incidence of LBW increased to 2.70-fold (95%CI, 1.92, 3.80) and the incidence of SGA increased to 2.13-fold(95%CI, 1.50, 3.02). CONCLUSIONS: The study found an inverse correlation between UA levels and birth weight. High UA levels were associated with increased risk of LBW/SGA, particularly in third trimester. GH or PE complicated by hyperuricemia were found to have significantly higher risk of developing LBW/SGA. This relationship also existed in pregnant women with BMI < 25.


Assuntos
Hipertensão Induzida pela Gravidez , Hiperuricemia , Nascimento Prematuro , Recém-Nascido , Feminino , Gravidez , Humanos , Ácido Úrico , Peso ao Nascer , Recém-Nascido Pequeno para a Idade Gestacional , Estudos de Coortes , Estudos Retrospectivos , Hiperuricemia/epidemiologia , China/epidemiologia , Recém-Nascido de Baixo Peso , Nascimento Prematuro/epidemiologia
17.
Intern Med J ; 54(3): 473-482, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37552622

RESUMO

BACKGROUND AND AIMS: The clinical effects of multivessel interventions in patients with unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI), multivessel disease (MVD) and chronic kidney disease (CKD) remain uncertain. This study aimed to investigate the safety and effectiveness of intervention in non-culprit lession(s) among this cohort. METHODS: We consecutively included patients diagnosed with UA/NSTEMI, MVD and CKD between January 2008 and December 2018 at our centre. After successful percutaneous coronary intervention (PCI), we compared 48-month overall mortality between those undergoing multivessel PCI (MV-PCI) through a single-procedure or staged-procedure approach and culprit vessel-only PCI (CV-PCI) after 1:1 propensity score matching. We conducted stratified analyses and tests for interaction to investigate the modifying effects of critical covariates. Additionally, we recorded the incidence of contrast-induced nephropathy (CIN) to assess the perioperative safety of the two treatment strategies. RESULTS: Of the 749 eligible patients, 271 pairs were successfully matched. Those undergoing MV-PCI had reduced all-cause mortality (hazard ratio (HR): 0.67, 95% confidence interval (CI): 0.48-0.67). Subgroup analysis showed that those with advanced CKD (estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2 ) could not benefit from MV-PCI (P = 0.250), and the survival advantage also tended to diminish in diabetes (P interaction < 0.01; HR = 0.95, 95% CI = 0.65-1.45). Although the staged-procedure approach (N = 157) failed to bring additional survival benefits compared to single-procedure MV-PCI (N = 290) (P = 0.460), it showed a tendency to decrease the death risk. CIN risks in MV-PCI and CV-PCI groups were not significantly different (risk ratio = 1.60, 95% CI = 0.94-2.73). CONCLUSION: Among patients with UA/NSTEMI and non-diabetic CKD and an eGFR > 30 mL/min/1.73 m2 , MV-PCI was associated with a reduced risk of long-term death but did not increase the incidence of CIN during the management of MVD compared to CV-PCI. And staged procedures might be a preferable option over single-procedure MV-PCI.


Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio sem Supradesnível do Segmento ST , Intervenção Coronária Percutânea , Insuficiência Renal Crônica , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Intervenção Coronária Percutânea/métodos , Angina Instável , Insuficiência Renal Crônica/complicações , Rim , Resultado do Tratamento
18.
J Synchrotron Radiat ; 31(Pt 1): 65-76, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37933847

RESUMO

Recent technical developments and the performance of the X-ray photon correlation spectroscopy (XPCS) method over the ultra-small-angle range with the Extremely Brilliant Source (EBS) at the ESRF are described. With higher monochromatic coherent photon flux (∼1012 photons s-1) provided by the EBS and the availability of a fast pixel array detector (EIGER 500K detector operating at 23000 frames s-1), XPCS has become more competitive for probing faster dynamics in relatively dilute suspensions. One of the goals of the present development is to increase the user-friendliness of the method. This is achieved by means of a Python-based graphical user interface that enables online visualization and analysis of the processed data. The improved performance of XPCS on the Time-Resolved Ultra-Small-Angle X-ray Scattering instrument (ID02 beamline) is demonstrated using dilute model colloidal suspensions in several different applications.

19.
Front Immunol ; 14: 1282890, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38053999

RESUMO

Changes in lifestyle induce an increase in patients with hyperuricemia (HUA), leading to gout, gouty arthritis, renal damage, and cardiovascular injury. There is a strong inflammatory response in the process of HUA, while dysregulation of immune cells, including monocytes, macrophages, and T cells, plays a crucial role in the inflammatory response. Recent studies have indicated that urate has a direct impact on immune cell populations, changes in cytokine expression, modifications in chemotaxis and differentiation, and the provocation of immune cells by intrinsic cells to cause the aforementioned conditions. Here we conducted a detailed review of the relationship among uric acid, immune response, and inflammatory status in hyperuricemia and its complications, providing new therapeutic targets and strategies.


Assuntos
Artrite Gotosa , Gota , Hiperuricemia , Humanos , Hiperuricemia/complicações , Hiperuricemia/metabolismo , Ácido Úrico/metabolismo , Gota/tratamento farmacológico , Artrite Gotosa/tratamento farmacológico , Inflamação/complicações
20.
Int J Gen Med ; 16: 6065-6072, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38148885

RESUMO

Background: P-wave terminal force in lead V1 (PtfV1) irregularity has been associated with various cardiovascular conditions, including atrial fibrillation, left ventricular diastolic dysfunction, valvular heart disease, congestive heart failure, stroke, and mortality. However, its prognostic value for unstable angina (UA) has not been extensively studied. To address this knowledge gap, this study aimed to evaluate the long-term predictive significance of PtfV1 at discharge for UA patients. Methods: A total of 707 patients with newly diagnosed UA were included in this study. PtfV1 measurements were recorded at admission and discharge. PtfV1(+) was defined as an absolute value above 0.04mm·s, while PtfV1(-) was defined as an absolute value below 0.04mm·s. Based on their PtfV1 values at discharge, patients were categorized into two groups: PtfV1(-) and PtfV1(+). Univariate and multivariate regression analyses were conducted to identify variables that could potentially contribute to the risk of UA. Results: Univariate analysis revealed a higher incidence of total adverse outcomes and major adverse cardiovascular events (MACE) in the PtfV1(+) group compared to the PtfV1(-) group, with a risk ratio (RR) of 2.006 [95% confidence interval (95% CI): 1.389-2.896] for total outcomes and an RR of 2.759 (95% CI: 1.870-4.070) for MACE. After adjusting for confounding factors through multivariate analysis, participants with PtfV1(+) had a 46% increased risk [adjusted hazard ratio (HR): 1.458; 95% CI: 1.010-2.104]for total adverse outcomes and an 86% increased risk (adjusted HR: 1.863; 95% CI: 1.246-2.786) for MACE compared to those with PtfV1(-). Conclusion: The presence of PtfV1(+) at discharge is an independent predictor of poor outcomes and provides extended prognostic information for UA patients.

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