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1.
Molecules ; 29(15)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39125009

RESUMO

Human pharyngeal squamous cell carcinoma (HPSCC) is the most common malignancy in the head and neck region, characterized by high mortality and a propensity for metastasis. Fucoxanthin, a carotenoid isolated from brown algae, exhibits pharmacological properties associated with the suppression of tumor proliferation and metastasis. Nevertheless, its potential to inhibit HPSCC proliferation and metastasis has not been fully elucidated. This study represents the first exploration of the inhibitory effects of fucoxanthin on two human pharyngeal squamous carcinoma cell lines (FaDu and Detroit 562), as well as the mechanisms underlying those effects. The results showed dose-dependent decreases in the proliferation, migration, and invasion of HPSCC cells after fucoxanthin treatment. Further studies indicated that fucoxanthin caused a significant reduction in the expression levels of proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, as well as the downstream proteins matrix metalloproteinase (MMP)-2 and MMP-9. Specific activators of PI3K/AKT reversed the effects of fucoxanthin on these proteins, as well as on cell proliferation and metastasis, in FaDu and Detroit 562 cells. Molecular docking assays confirmed that fucoxanthin strongly interacted with PI3K, AKT, mTOR, MMP-2, and MMP-9. Overall, fucoxanthin, a functional food component, is a potential therapeutic agent for HPSCC.


Assuntos
Movimento Celular , Proliferação de Células , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Xantofilas , Humanos , Serina-Treonina Quinases TOR/metabolismo , Xantofilas/farmacologia , Xantofilas/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proliferação de Células/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Neoplasias Faríngeas/tratamento farmacológico , Neoplasias Faríngeas/patologia , Neoplasias Faríngeas/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Metástase Neoplásica , Simulação de Acoplamento Molecular
2.
Synth Syst Biotechnol ; 9(4): 853-860, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39139857

RESUMO

Nosema ceranae, a parasite that parasitizes and reproduces in the gut of honeybees, has become a serious threat to the global apiculture industry. RNA interference (RNAi) technology can be used to inhibit N. ceranae growth by targeting silencing the thioredoxin reductase (TrxR) in N. ceranae. However, suitable carriers are one of the reasons limiting the application of RNAi due to the easy degradation of dsRNA in honeybees. As a vesicle composed of a lipid bilayer, liposomes are a good carrier for nucleic acid delivery, but studies in honeybees are lacking. In this study, liposomes were used for double-stranded RNA (dsRNA) dsTrxR delivery triggering RNAi to inhibit the N. ceranae growth in honeybees. Compared to naked dsTrxR, liposome-dsTrxR reduced N. ceranae numbers in the midgut and partially restored midgut morphology without affecting bee survival and gut microbial composition. The results of this study confirmed that liposomes could effectively protect dsRNA from entering the honeybee gut and provide a reference for using RNAi technology to suppress honeybee pests and diseases.

3.
Mar Pollut Bull ; 207: 116834, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39142052

RESUMO

Denitrification, anammox, and DNRA are three important nitrogen (N) reduction pathways in estuarine sediments. Although salinity is an important variables controlling microbial growth and activities, knowledge about the effects of changing salinity on those three processes in estuarine and coastal wetland sediments are not well understood. Herein, we performed a 60-d microcosms experiment with different salinities (0, 5, 15, 25 and 35 ‰) to explore the vital role of salinity in controlling N-loss and N retention in estuarine wetland sediments. The results showed that sediment organic matter, sulfide, and nitrate (NO3-) were profoundly decreased with increasing salinity, while sediment ammonium (NH4+) and ferrous (Fe2+) varied in reverse patterns. Meanwhile, N-loss and N retention rates and associated gene abundances were differentially inhibited with increasing salinity, while the contributions of denitrification, anammox, and DNRA to total nitrate reduction were apparently unaffected. Moreover, denitrification rate was the most sensitive to salinity, and then followed by DNRA, while anammox was the weakest among these three processes. In other words, anammox bacteria showed a wide range of salinity tolerance, while both denitrification and DNRA reflected a relatively limited dynamic range of it. Our findings could provide insights into temporal interactive effects of salinity on sediment physico-chemical properties, N reduction rates and associated gene abundances. Our findings can improve understanding of the effects of saltwater incursion on the N fate and N balance in estuarine and coastal sediments.

4.
J Environ Manage ; 368: 122166, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39154385

RESUMO

The risk of pharmaceuticals and personal care products (PPCPs) has been paid more attention after the outbreak of COVID-19, threatening the ecology and human health resulted from the massive use of drugs and disinfectants. Wastewater treatment plants are considered the final stop to restrict PPCPs from wide spreading into the environment, but the performance of conventional treatment is limited due to their concentrations and characteristics. Previous studies have shown the unreplaceable capability of moving bed-biofilm reactor (MBBR) as a cost-effective method with layered microbial structure for treating wastewater even with toxic compounds. The biofilm community and microbial interactions are essential for the MBBR process in completely degrading or converting types of PPCPs to secondary metabolites, which still need further investigation. This review starts with discussing the initiation of MBBR formation and its influencing parameters according to the research on MBBRs in the recent years. Then the efficiency of MBBRs and the response of biofilm after exposure to PPCPs are further addressed, followed by the bottlenecks proposed in this field. Some critical approaches are also recommended for mitigating the deficiencies of MBBRs based on the recently published publications to reduce the environmental risk of PPCPs. Finally, this review provides fundamental information on PPCPs removal by MBBRs with the main focus on microbial interactions, promoting the MBBRs to practical application in the real world of wastewater treatment.

5.
Sci Total Environ ; : 175556, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39153638

RESUMO

BACKGROUND: Recently pilot published city-level air quality health index (AQHI) provides a useful tool for communicating short-term health risks of ambient air pollution, but fails to account for intracity spatial heterogeneity in co-exposure and associated population health impacts. This study aims to assess the association between individual-level air pollution exposure and health risks, and attempts to develop a refined spatiotemporal AQHI (ST-AQHI) for composite air pollution exposure scenarios. METHODS: A three-stage analysis was conducted through integrating province-wide death surveillance data and high-resolution gridded estimates of air pollution and climate factors spanning 2016-2019 in Jiangsu Province, eastern China. We analyzed a total of 1,905,209 nonaccidental death cases, comprising 785,567 from circulatory diseases and 247,336 from respiratory diseases. First, an individual-level case-crossover design was employed to quantify the short-term risk of nonaccidental mortality associated with residential exposure to individual pollutant (i.e., PM2.5, NO2, O3, and SO2). Second, we accumulated and scaled the excess risks arising from multiple pollutants to formulate daily gridded ST-AQHI estimates at 0.1°â€¯× 0.1°, dividing exposure-related risks into low (0 to 3), moderate (4 to 6), high (7 to 9), and extremely high (10+) levels. Finally, the effectiveness of ST-AQHI as composite risk communication was validated through checking the dose-response associations of individual ST-AQHI exposure with death from major circulatory and respiratory causes via repeating case-crossover analyses. RESULTS: In the first-stage analysis, for each 10-µg/m3 rise in PM2.5, NO2, O3, and SO2 exposure at lag-01 day, population risk of nonaccidental death was increased by 0.8 % (95 % confidence interval: 0.7 %, 0.9 %), 1.9 % (1.7 %, 2.0 %), 0.4 % (0.3 %, 0.5 %), and 4.1 % (3.7 %, 4.5 %), respectively. Spatiotemporal distribution of ST-AQHI exhibited a consistent declining trend throughout the study period (2016-2019), with annual average ST-AQHI decreasing from 5.2 ±â€¯1.3 to 4.0 ±â€¯1.0 and high-risk days dropping from 15.8 % (58 days) to 1.6 % (6 days). Exposure associated health risks showed great intracity- and between-city heterogeneities. In the validation analysis, ST-AQHI demonstrated approximately linear, threshold-free associations with multiple death events from major cardiopulmonary causes, suggesting excellent performance in predicting exposure-related health risks. Specifically, each 1-unit rise in ST-AQHI was significantly associated with an excess risk of 2.0 % (1.8 %, 2.1 %) for nonaccidental death, 2.3 % (2.1 %, 2.6 %) for overall circulatory death, and 2.7 % (2.3 %, 3.1 %) for overall respiratory death, as well as 1.7 %-3.0 % for major cardiopulmonary sub-causes. CONCLUSIONS: ST-AQHI developed via refined exposure and health risk assessment performed well in predicting spatiotemporal heterogeneity of death risks related to multiple air pollutants. ST-AQHI may hold significant importance in offering personalized guidance for communicating intracity air pollution-related health risks.

6.
Foods ; 13(15)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39123625

RESUMO

Alternariol (AOH), an emerging mycotoxin, inevitably exists widely in various food and feed commodities with cereals and fruits being particularly susceptible, raising global concerns over its harm to human and livestock health. The development of eco-friendly and efficient strategies to decontaminate AOH has been an urgent task. This study provided insight into the utilization of crude soybean hull peroxidase as a powerful biocatalyst for degrading AOH. The results confirmed that crude soybean hull peroxidase (SHP) could catalyze the oxidation of AOH by use of H2O2 as a co-substrate. The optimum reaction conditions for SHP-catalyzed AOH degradation were recorded at pH 4.0-8.0, at 42-57 °C, and at H2O2 concentration of 100-500 µM. Mass analysis elucidated the degradation of AOH through hydroxylation and methylation by crude SHP. Moreover, toxicological analysis indicated that crude SHP-catalyzed AOH degradation detoxified the hepatotoxicity of this mycotoxin. The performance of crude SHP to degrade AOH in food matrices was further evaluated, and it was found that the enzyme agent could achieve AOH degradation by 77% in wheat flour, 84% in corn flour, 34% in grape juice, and 26% in apple juice. Collectively, these findings establish crude SHP as a promising candidate for effective AOH degradation, with potential applications in the food and feed industry.

7.
J Comput Chem ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39135268

RESUMO

The two-dimensional (2D) monolayer material MoSi2N4 was successfully synthesized in 2020[Hong et al., Science 369, 670, (2020)], exhibiting a plethora of new phenomena and unusual properties, with good stability at room temperature. However, MA2Z4 family monolayer materials involve primarily transition metal substitutions for M atoms. In order to address the research gap on lanthanide and actinide MA2Z4 materials, this work conducts electronic structure calculations on novel 2D MSi2N4 (M = La, Eu) monolayer materials by employing first-principles methods and CASTEP. High carrier mobility is discovered in the indirect bandgap semiconductor 2D LaSi2N4 monolayer (~5400 cm2 V-1 s-1) and in the spin (spin-down channel) carrier mobility of the half-metallic ferromagnetic EuSi2N4 monolayer (~2800 cm2 V-1 s-1). EuSi2N4 monolayer supplements research on spin carrier mobility in half-metallic ferromagnetic monolayer materials at room temperature and possesses a magnetic moment of 5 µB, which should not be underestimated. Furthermore, due to the unique electronic band structure of EuSi2N4 monolayer (with the spin-up channel exhibiting metallic properties and the spin-down channel exhibiting semiconductor properties), it demonstrates a 100% spin polarization rate, presenting significant potential applications in fields such as magnetic storage, magnetic sensing, and spintronics.

8.
ACS Omega ; 9(32): 35197-35208, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39157101

RESUMO

A series of minimally sized regular dodecahedron-embedded metallofullerene REC20 clusters (RE = Sc, Y, La, Ce, Pr, Nd, Pm, Sm, Eu, and Gd) as basic units of nanoassembled materials with tunable magnetism and UV sensitivity have been explored using density functional theory (DFT). The contribution of the 4f orbital of the rare earth atom at the center of the C20 cage to the frontier molecular orbital of REC20 gives the REC20 cluster additional stability. The AdNDP orbitals of the four REC20 superatoms that conform to the spherical jellium model indicate that through natural population analysis and spin density diagrams, we observe a monotonic increase in the magnetic moment from Ce to Gd. This is attributed to the increased number of unpaired electrons in the 4f orbitals of lanthanide rare earth atoms. The UV-visible spectrum of REC20 clusters shows strong absorption in the mid-UV and near-UV bands. REC20 clusters encapsulating lanthanide rare earth atoms stand out for their tunable magnetism, UV sensitivity, and stability, making them potential new self-assembly materials.

10.
Data Brief ; 55: 110703, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39105063

RESUMO

Real-time monitoring of milling parameters is essential to improve machining efficiency and quality, especially for the workpieces with complex geometry. Its main task is to build the relationship between the parameters and the monitoring data. As the relationship is challenging to be established solely through mechanism-driven or data-driven methods, the physics informed method, based on prior physical laws between physical signals and milling parameters, becomes the optimal method. However, this method is limited due to the lack of a high-quality dataset. Therefore, a multi-sensor monitoring dataset for the milling process with various milling parameters and milling materials is built. The variables include cutting depth, cutting width, feed rate, spindle speed and workpiece materials (aluminium alloy 7030 and CK45 steel). The multi-sensor includes force, vibration, noise, and current. A dataset comprising 115 samples is built, including 100 samples collected using the 'all factors' method, and 15 slot milling samples using two different workpiece materials. The 15 slot milling samples are used to calibrate mechanical milling force coefficients, which is beneficial for developing a physics-informed machine learning algorithm.

11.
Phys Rev E ; 110(1-1): 014132, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39160973

RESUMO

The fluctuation of the quantum Otto engine has recently received a lot of attention, while applying the many body with a long-range interaction to a quantum heat engine may enhance our ability of controlling it. Using the two-point measurement and its generalization, we explore the fluctuation theorem of work and heat in a single stroke as well as in a cycle. We discover that the fluctuations of work in a cycle as well as fluctuations of heat in a single stroke or cycle can be connected to the fluctuation of work in a single stroke. Then we numerically investigate the effect of a long-range interaction on these fluctuation theorems, and our result shows that the fluctuation can be improved by manipulating the long-range interaction.

12.
Anal Bioanal Chem ; 416(22): 4849-4860, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39008068

RESUMO

This paper reports a flexible glucose biosensor which is modified by a reduced-swelling and conductive zwitterionic hydrogel enzyme membrane that contains two forms of chemical cross-links. One chemical cross-linking is induced by thermal initiators and forms the basal network of the hydrogel. Another cross-linking is achieved by the coordination interactions between the multivalent metal ion Al3+ and anionic group -COO- of zwitterionic poly-carboxy betaine (pCBMA), which significantly increase the cross-linking density of the zwitterionic hydrogel, improving the reduced-swelling property and reducing the pore size. The better reduced-swelling property and reduced diameters of pores within the zwitterionic hydrogel make less glucose oxidase (GOx) leakage, thus significantly improving the enzyme membrane's service life. By introducing the Al3+ and Cl-, the conductivity of the zwitterionic hydrogel is enhanced approximately 10.4-fold. According to the enhanced conductivity, the reduced-swelling property, and the high GOx loading capacity of the zwitterionic hydrogel, the sensitivity of the biosensor with GOx/pCBMA-Al3+ is significantly improved by 5 times and has a long service life. Finally, the proposed GOx/pCBMA-Al3+ biosensor was applied in non-invasive blood glucose detection on the human body, verifying the capability in practice.


Assuntos
Técnicas Biossensoriais , Condutividade Elétrica , Enzimas Imobilizadas , Glucose Oxidase , Glucose , Técnicas Biossensoriais/métodos , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Enzimas Imobilizadas/química , Glucose/análise , Glucose/química , Hidrogéis/química , Humanos , Membranas Artificiais , Glicemia/análise
13.
Int J Chron Obstruct Pulmon Dis ; 19: 1707-1719, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39081777

RESUMO

Background: Pulmonary rehabilitation (PR) is an effective intervention for people with chronic obstructive pulmonary disease (COPD). However, fewer than 5% of eligible individuals receive pulmonary rehabilitation, largely due to limited by the accessibility of rehabilitation and difficulties associated with travel and transport. Supervised home-based tele-rehabilitation (SHTR) is an alternative model to center-based pulmonary rehabilitation. We will determine whether supervised home-based tele-rehabilitation is non-inferior to center-based pulmonary rehabilitation. Methods: The participants will undergo an 8-week rehabilitation program. Pulmonary rehabilitation comprises four main modules: exercise training, education, nutritional support, and psychological and behavioral interventions. We mainly focus on the module of exercise training and education. The education module includes information on exercise training, nutrition, and psychology, which are presented in an educational booklet provided to each participant. Blinded assessors will evaluate the outcomes at baseline, post-intervention, and 6 months after the intervention. The primary outcome is the change in the 6-minute walking distance. Secondary outcomes will assess changes in the patients' 1-minute sit-to-stand test, maximal inspiratory pressure (MIP), scales (CAT, mMRC, HAD), diaphragm ultrasound (TD, DE, DIF), changes in extrathoracic muscle volume and mass, completion rate of patient exercise prescriptions, occurrence of adverse events, as well as disease exacerbation and rehospitalization rates after rehabilitation and during the 6-month follow-up. Discussion: In order to improve the accessibility of pulmonary rehabilitation and patient-related outcomes, it is necessary to propose an alternative model of pulmonary rehabilitation. This trial will establish whether a supervised home-based tele-rehabilitation is not inferior to traditional center-based pulmonary rehabilitation. Trial Registration: Chinese Clinical Trial Registry ChiCTR2300076969. Registered on October 25, 2023.


Assuntos
Terapia por Exercício , Tolerância ao Exercício , Serviços de Assistência Domiciliar , Estudos Multicêntricos como Assunto , Doença Pulmonar Obstrutiva Crônica , Recuperação de Função Fisiológica , Telerreabilitação , Humanos , Doença Pulmonar Obstrutiva Crônica/reabilitação , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , China , Resultado do Tratamento , Terapia por Exercício/métodos , Fatores de Tempo , Pulmão/fisiopatologia , Pessoa de Meia-Idade , Centros de Reabilitação , Masculino , Educação de Pacientes como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Feminino , Idoso , Estudos de Equivalência como Asunto , Estado Funcional , Teste de Caminhada
15.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(7): 690-694, 2024 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-39014944

RESUMO

OBJECTIVES: To investigate the application of endoscopic retrograde cholangiopancreatography (ERCP) in children and the risk factors for post-ERCP pancreatitis (PEP). METHODS: A retrospective analysis was conducted on the clinical data of 66 children, aged ≤16 years, who underwent ERCP for pancreaticobiliary diseases at the Gastrointestinal Endoscopy Center of the Second Affiliated Hospital of Kunming Medical University from September 2013 to September 2023. The incidence rate of PEP and the risk factors for the development of PEP were analyzed. RESULTS: A total of 78 ERCP procedures were performed on 66 children, with 5 diagnostic ERCPs, 69 therapeutic ERCPs, and 4 failed procedures. The success rate of ERCP operations was 95% (74/78). There were 17 cases of PEP in total, with an incidence rate of 22%. In the PEP group, the proportion of children with normal preoperative bilirubin and the proportion of guidewire insertion into the pancreatic duct during surgery were higher than in the non-PEP group (P<0.05). The multivariate logistic regression analysis showed that guidewire insertion into the pancreatic duct was an independent risk factor for PEP (P<0.05). CONCLUSIONS: With the increasing application of ERCP in children with pancreaticobiliary diseases, it is important to select an appropriate intubation technique during surgery to avoid blindly entering the guidewire into the pancreatic duct and reduce the occurrence of PEP.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Pancreatite , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Criança , Masculino , Pancreatite/etiologia , Pancreatite/prevenção & controle , Feminino , Fatores de Risco , Estudos Retrospectivos , Pré-Escolar , Adolescente , Modelos Logísticos , Lactente
16.
J Phys Chem A ; 128(28): 5459-5472, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38973649

RESUMO

In this study, we employ density functional theory along with the artificial bee colony algorithm for cluster global optimization to explore the low-lying structures of TeBnq (n = 3-16, q = 0, -1). The primary focus is on reporting the structural properties of these clusters. The results reveal a consistent doping pattern of the tellurium atom onto the in-plane edges of planar or quasi-planar boron clusters in the most energetically stable isomers. Additionally, we simulate the photoelectron spectra of the cluster anions. Through relative stability analysis, we identify three clusters with magic numbers -TeB7-, TeB10, and TeB12. The aromaticity of these clusters is elucidated using adaptive natural density partitioning (AdNDP) and magnetic properties analysis. Notably, TeB7- exhibits a perfect σ-π doubly aromatic structure, while TeB12 demonstrates strong island aromaticity. These findings significantly contribute to our understanding of the structural and electronic properties of these clusters.

17.
BMC Med Imaging ; 24(1): 165, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956579

RESUMO

BACKGROUND: Pneumoconiosis has a significant impact on the quality of patient survival due to its difficult staging diagnosis and poor prognosis. This study aimed to develop a computer-aided diagnostic system for the screening and staging of pneumoconiosis based on a multi-stage joint deep learning approach using X-ray chest radiographs of pneumoconiosis patients. METHODS: In this study, a total of 498 medical chest radiographs were obtained from the Department of Radiology of West China Fourth Hospital. The dataset was randomly divided into a training set and a test set at a ratio of 4:1. Following histogram equalization for image enhancement, the images were segmented using the U-Net model, and staging was predicted using a convolutional neural network classification model. We first used Efficient-Net for multi-classification staging diagnosis, but the results showed that stage I/II of pneumoconiosis was difficult to diagnose. Therefore, based on clinical practice we continued to improve the model by using the Res-Net 34 Multi-stage joint method. RESULTS: Of the 498 cases collected, the classification model using the Efficient-Net achieved an accuracy of 83% with a Quadratic Weighted Kappa (QWK) score of 0.889. The classification model using the multi-stage joint approach of Res-Net 34 achieved an accuracy of 89% with an area under the curve (AUC) of 0.98 and a high QWK score of 0.94. CONCLUSIONS: In this study, the diagnostic accuracy of pneumoconiosis staging was significantly improved by an innovative combined multi-stage approach, which provided a reference for clinical application and pneumoconiosis screening.


Assuntos
Aprendizado Profundo , Pneumoconiose , Humanos , Pneumoconiose/diagnóstico por imagem , Pneumoconiose/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Radiografia Torácica/métodos , Idoso , Adulto , Redes Neurais de Computação , China , Diagnóstico por Computador/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos
18.
Front Cardiovasc Med ; 11: 1417593, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39049957

RESUMO

Uromodulin, also referred to as Tamm Horsfall protein (THP), is a renal protein exclusively synthesized by the kidneys and represents the predominant urinary protein under normal physiological conditions. It assumes a pivotal role within the renal system, contributing not only to ion transport and immune modulation but also serving as a critical factor in the prevention of urinary tract infections and kidney stone formation. Emerging evidence indicates that uromodulin may serve as a potential biomarker extending beyond renal function. Recent clinical investigations and Mendelian randomization studies have unveiled a discernible association between urinary regulatory protein levels and cardiovascular events and mortality. This review primarily delineates the intricate relationship between uromodulin and cardiovascular disease, elucidates its predictive utility as a novel biomarker for cardiovascular events, and delves into its involvement in various physiological and pathophysiological facets of the cardiovascular system, incorporating recent advancements in corresponding genetics.

19.
Cell Death Differ ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060422

RESUMO

There is an unmet clinical need for pharmacologic treatment for metabolic dysfunction-associated steatotic liver disease (MASLD). Hepatocyte cell death is a hallmark of this highly prevalent chronic liver disease, but the dominant type of cell death remains uncertain. Here we report that ferroptosis, an iron-catalyzed mode of regulated cell death, contributes to MASLD. Unsupervised clustering in a cohort of biopsy-proven MASLD patients revealed a subgroup with hepatic ferroptosis signature and lower glutathione peroxidase 4 (GPX4) levels. Likewise, a subgroup with reduced ferroptosis defenses was discerned in public transcriptomics datasets. Four weeks of choline-deficient L-amino acid-defined high-fat diet (CDAHFD) induced MASLD with ferroptosis in mice. Gpx4 overexpression did not affect steatohepatitis, instead CDAHFD protected from morbidity due to hepatocyte-specific Gpx4 knockout. The ferroptosis inhibitor UAMC-3203 attenuated steatosis and alanine aminotransferase in CDAHFD and a second model, i.e., the high-fat high-fructose diet (HFHFD). The effect of monounsaturated and saturated fatty acids supplementation on ferroptosis susceptibility was assessed in human HepG2 cells. Fat-laden HepG2 showed a drop in ferroptosis defenses, increased phosphatidylglycerol with two polyunsaturated fatty acid (PUFA) lipid tails, and sustained ferroptosis sensitivity. In conclusion, this study identified hepatic ferroptosis as a detrimental factor in MASLD patients. Unexpectedly, non-PUFA supplementation to hepatocytes altered lipid bilayer composition to maintain ferroptosis sensitivity. Based on findings in in vivo models, ferroptosis inhibition represents a promising therapeutic target in MASLD.

20.
Aging (Albany NY) ; 16(13): 10813-10831, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38980253

RESUMO

BACKGROUND: Bladder cancer (BLCA), which develops from the upper endometrial of the bladder, is the sixth most prevalent cancer across the globe. WDHD1 (WD repeat and HMG-box DNA binding protein 1 gene) directly affects signaling, the cell cycle, and the development of the cell skeleton. Uncertainty surrounds WDHD1's function in BLCA immunity and prognosis, though. MATERIALS AND METHODS: Using weighed gene co-expression network analysis (WGCNA), initially, we first identified 32 risk factors in genes with differential expression for this investigation. Then, using a variety of bioinformatic techniques and experimental validation, we examined the connections between WDHD1 and BLCA expression, clinical pathological traits, WDHD1-related proteins, upper-skin-intermediate conversion (EMT), immune cell immersion, convergence factors, immune markers, and drug sensitivity. RESULT: The findings demonstrated that we constructed a 32-gene risk-predicting model where WDHD1 was elevated as a representative gene expression in BLCA and related to a range of clinical traits. Furthermore, high WDHD1 expression was a standalone predictor associated with a worse survival rate. The most commonly recruited cells and their evolutionary patterns were highlighted to better comprehend WDHD1's function in cancer. High WDHD1 expression was associated with many aspects of immunology. Finally, the study found that individuals with high expression of WDHD1 were drug-sensitive to four different broad-spectrum anti-cancer drugs. CONCLUSION: These results describe dynamic changes in the tumor microenvironment in BLCA and provide evidence for the hypothesis that WDHD1 is a novel biomarker of tumor development. WDHD1 may therefore be a useful target for the detection and management of BLCA.


Assuntos
Biomarcadores Tumorais , Transição Epitelial-Mesenquimal , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Prognóstico , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes
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