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1.
Food Chem ; 431: 137099, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37572481

RESUMO

The texture, flavor, performance and nutrition of foods are affected by their physical properties during processing, cooking, storage, and shelf life. In addition to chemical, physical, and enzymatic modification methods, polysaccharide addition is also considered a safe, effective, and convenient food modification strategy. However, thus far, literature review on the effects of polysaccharides on the physical properties of foods is few. Therefore, the present work reviews the effects of polysaccharides on water retention capacity, rheological property, suspension ability, viscoelasticity, emulsifying property, gelling property, stability, and starch regeneration and digestion. Furthermore, the existing problems and future recommendations during food physical property modification by polysaccharides are presented. This work aims to provide some theoretical references for future research, development, and application of polysaccharides on food physical property modification.


Assuntos
Polissacarídeos , Amido , Polissacarídeos/química , Alimentos , Culinária , Géis
2.
Food Chem ; 431: 137128, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37591138

RESUMO

Bacillus cereus is a pathogenic bacterium that causes food contamination, resulting in food poisoning such as diarrhea and emesis. Therefore, it is crucial to develop effective strategies to control this bacterium. In this study, we isolated and characterized a novel B. cereus phage, named DZ1. Morphological and genomic analyses revealed that phage DZ1 is a new species belonging to the Andromedavirus genus. Phage DZ1 was tolerant to a wide range of pH values (5-9), temperatures (4-55 â„ƒ), and high concentrations of NaCl solution (1000 mM). B. cereus with 21 different sequence types (STs) can be lysed by phage DZ1. Importantly, phage DZ1 inhibited B. cereus growth in spiked rice substrates or milk up to 36 and 72 h, respectively, with suppression of 3 log. Therefore, phage DZ1 is a useful biocontrol agent for the control of B. cereus in the food industry.


Assuntos
Fagos Bacilares , Cactaceae , Animais , Bacillus cereus , Diarreia , Leite
3.
Talanta ; 266(Pt 2): 125050, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37598442

RESUMO

The establishment of sensitive and facile colorimetric platform based on the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) system is of great significance for in vitro diagnosis. Herein, we develop a dual-enzyme cascade amplification strategy based on CRISPR-Cas12a and glucose oxidase (GOx) for instrument-free and sensitive detection of target analytes. HPV-16 DNA as the model nucleic acid target directly initiated CRISPR-Cas12a-based signal transduction, resulting in the enzymatic cleavage of ssDNA linker and the release of GOx from magnetic nanoparticles 1 (MNPs1). Following simple magnetic separation, the supernatant containing GOx was taken out and used to catalyze the substrate, resulting in a visually detectable color change. The detection limit (LOD) of HPV-16 DNA was as low as 1 pM, and the entire process could be completed within 70 min without the need for expensive equipment. Notably, the dual-enzyme cascade amplification strategy was successfully applied to the detection of non-nucleic acid targets, such as ATP, via a simple signal transduction process. The visual LOD for ATP detection reaches 2.5 µM. The approach provides a robust, sensitive and reliable point-of-care biosensing platform for the detection of target analytes.


Assuntos
Sistemas CRISPR-Cas , Ácidos Nucleicos , Colorimetria , Papillomavirus Humano 16/genética , Catálise , Glucose Oxidase , Trifosfato de Adenosina
4.
Front Neurosci ; 17: 1227491, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37662098

RESUMO

Brain diseases, including neurodegenerative diseases and neuropsychiatric diseases, have long plagued the lives of the affected populations and caused a huge burden on public health. Functional magnetic resonance imaging (fMRI) is an excellent neuroimaging technology for measuring brain activity, which provides new insight for clinicians to help diagnose brain diseases. In recent years, machine learning methods have displayed superior performance in diagnosing brain diseases compared to conventional methods, attracting great attention from researchers. This paper reviews the representative research of machine learning methods in brain disease diagnosis based on fMRI data in the recent three years, focusing on the most frequent four active brain disease studies, including Alzheimer's disease/mild cognitive impairment, autism spectrum disorders, schizophrenia, and Parkinson's disease. We summarize these 55 articles from multiple perspectives, including the effect of the size of subjects, extracted features, feature selection methods, classification models, validation methods, and corresponding accuracies. Finally, we analyze these articles and introduce future research directions to provide neuroimaging scientists and researchers in the interdisciplinary fields of computing and medicine with new ideas for AI-aided brain disease diagnosis.

5.
Open Forum Infect Dis ; 10(8): ofad425, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37663088

RESUMO

Background: Bronchiectasis is a chronic inflammatory respiratory disease mainly caused by pathogenic infections. However, standard methods of pathogen detection show prolonged cycle durations and unsatisfactory sensitivity and detection rates. Macrogenomic next-generation sequencing (mNGS) emerges as a promising technique for swift, effective, and unbiased pathogen detection and subsequent data interpretation. Methods: Here, a retrospective analysis of 93 patients with suspected bronchiectasis was performed to assess the clinical applicability of mNGS. Bronchoalveolar alveolar lavage fluid (BALF) samples were collected from these subjects, followed by standard assays and mNGS separately. The turnaround time, detection rate, and pathogen identification using mNGS were compared with those of standard methods. Results: mNGS identified a greater number of bacteria (72 vs 16), fungi (26 vs 19), and viruses (14 vs 0) than standard methods. Specifically, the commonly identified bacteria were Haemophilus, Mycobacterium intracellulare, Pseudomonas, and Streptococcus pneumoniae, while the most detected fungi were Aspergillus and the most prevalent viruses were human herpesviruses. Of note, 29 out of 30 patients (96.67%) who received optimized treatment strategies based on mNGS results experienced recovery. Conclusions: Collectively, these findings suggest that mNGS has the potential to improve the diagnosis and treatment of bronchiectasis patients by enabling rapid and precise pathogen detection, which can lead to timely and effective treatment strategies.

6.
Front Microbiol ; 14: 1253969, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37664125

RESUMO

The organoleptic profile and quality of wine are affected by the presence of different non-Saccharomyces species and strains. Therefore, the identification and characterization of non-Saccharomyces yeasts are the first step to understand their function, and to develop a better strain selection program for winemaking. This study investigated the biodiversity of non-Saccharomyces yeasts associated with spontaneous fermentation of Cabernet Sauvignon wines from five sub-regions (Shi Zuishan, Yinchuan, Yu Quanying, Qing Tongxia and Hong Sibu) in Ningxia, China. Yeast species were identified by sequencing the 26S rRNA D1/D2 region, and strains at the subspecies level were discriminated using tandem repeat-tRNA (TRtRNA) PCR analysis. A total of 524 yeast colonies were isolated, and 19 non-Saccharomyces yeast species belonging to 10 genera were identified, including Aureobasidium pullulans, Cryptococcus albidus, Cryptococcus sp., C. flavescens, C. terrestris, C. magnus, Cystofilobasidium ferigula, Candida zemplinina, Filobasidium magnum, Filobasidium sp., F. elegans, Hanseniaspora uvarum, Metschnikowia pimensis, M. pulcherrima, Naganishia albida, Pichia kluyveri, P. kudriavzevii, Rhodotorula glutinis and R. graminis. Hanseniaspora uvarum, C. zemplinina, and M. pulcherrima were the three most dominated species, while other non-Saccharomyces species were only present in the early stage of spontaneous fermentations at different levels. Further, for the yeast discrimination at strain level, 34 profiles were obtained by amplification with primer pairs TtRNASC/5CAG, while 40 profiles were obtained with primer pairs TtRNASC/ISSR-MB. This study explored the diversity of non-Saccharomyces species in Ningxia, China, and made an important contribution of genetic resources for further strain development.

7.
World J Gastroenterol ; 29(31): 4809-4814, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37664155

RESUMO

BACKGROUND: Solitary rectal ulcer syndrome (SRUS) is a rare rectal disease with unknown etiology. Data on the genetic background in SRUS is lacking. CASE SUMMARY: Here, we report the first case of SRUS in a mother-son relationship. Gene sequencing was conducted on the whole family, which revealed an inherited CHEK2 p.H371Y mutation. The experiment preliminarily revealed that the CHEK2 mutation did not affect the expression of CHEK2 protein, but affected the function of CHEK2, resulting in the expression level changes of downstream genes such as CDC25A. CONCLUSION: SRUS is a genetic susceptibility disease where CHEK2 p.H371Y mutation may play a crucial role in the development and prognosis of SRUS.


Assuntos
Doenças do Colo , Doenças Retais , Humanos , Úlcera/genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Doenças Raras , Quinase do Ponto de Checagem 2/genética
8.
Lasers Med Sci ; 38(1): 198, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37656340

RESUMO

To compare the central corneal thickness (CCT) treated with small incision lenticule extraction (SMILE), femtosecond laser-assisted in situ keratomileusis (FS-LASIK), or laser-assisted subepithelial keratomileusis (LASEK) for myopia correction. This was a retrospective case series study. Patients who had completed 1-year follow-up after receiving SMILE, FS-LASIK, or LASEK at our hospital from January 2019 to July 2021 were included. Pentacam pachymetry was performed to measure the CCT. The predicted CCT reduction was obtained through laser platform. The measured CCT reduction was defined as the difference between the preoperative and postoperative CCT using Pentacam pachymetry. There were 100 eyes treated by SMILE, 100 eyes by FS-LASIK, and 100 eyes by LASEK. There was a significant difference in predicted CCT reduction among the three surgeries (P < 0.001), but no significant difference in measured CCT reduction postoperatively (PGroup = 0.373). At 1 year postoperatively, the CCT reduction was overestimated by 17.85 ± 5.36 µm in the SMILE group, underestimated by 4.31 ± 7.08 µm in the FS-LASIK group, and underestimated by 7.60 ± 8.28 µm in the LASEK group (PGroup < 0.001, PTime < 0.001). In the FS-LASIK group, the difference between predicted and measured CCT reduction was not related to the predicted CCT reduction (P = 0.095). The laser platform may overestimate the CCT reduction for SMILE and underestimate it for FS-LASIK and LASEK. FS-LASIK has a much higher level of accuracy in CCT reduction, which is not influenced by refractive correction.


Assuntos
Ceratectomia Subepitelial Assistida por Laser , Ceratomileuse Assistida por Excimer Laser In Situ , Miopia , Ferida Cirúrgica , Humanos , Estudos Retrospectivos , Miopia/cirurgia , Olho
9.
Int J Biol Macromol ; 253(Pt 1): 126636, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37657565

RESUMO

Abuse of antibiotics has led to excessive amounts of antibiotic residues in food and environment, thus enhancing pathogenic bacterium resistance and threatening human health. Therefore, searching and developing safe and green antibiotic alternatives are necessary. In this study, an Artemisia argyi leaf polysaccharide (AALP) fraction was extracted and analyzed. Chemical composition analysis showed that the carbohydrate, uronic acid, protein, and polyphenol content in AALP were 68.3 % ± 4.13 %, 9.4 % ± 0.86 %, 1.79 % ± 0.27 %, and 0.16 % ± 0.035 %, respectively. Chromatographic results suggested that AALP contained rhamnose, arabinose, glucosamine, galactose, glucose, xylose, mannose, galacturonic acid, and glucuronic acid in a molar ratio of 9.26, 1.35, 1.18, 3.04, 48.51, 2.33, 31.26, 3.93, and 9.08; the weight average molecular weight, number average molecular weight, and polydispersity of AALP were 5.41 kDa, 4.63 kDa, and 1.168, respectively. Fourier transform infrared spectroscopy indicated that AALP constituted the polysaccharide-specific groups of CH, CO, and OH. Meanwhile, AALP showed a dose-dependent inhibitory effect on Staphylococcus aureus in the inhibition zone assay, and the minimal inhibitory concentration was 1.25 mg/mL. Furthermore, AALP disrupted the cell wall, depolarized the inner membrane potential, and inhibited the activities of succinate dehydrogenase and malate dehydrogenase in S. aureus.

10.
J Cardiovasc Pharmacol Ther ; 28: 10742484231197559, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37661662

RESUMO

BACKGROUND: The effect of combined nicorandil and beta-adrenergic receptor blockers (BBs) compared with that of BBs alone on long-term clinical outcomes in patients with coronary artery disease (CAD) remains undetermined. METHODS: A multicenter retrospective cohort study was performed. Adult patients who had been hospitalized for CAD and treated for angina with a combination of nicorandil and BBs or BBs alone were included. The effect of different treatments on the cumulative incidence of major adverse cardiovascular event (MACE) and their components within a follow-up duration of 2.5 years were analyzed using Kaplan-Meier survival curves. An inverse probability of treatment weighting (IPTW) method was used to adjust for the possible effect of confounding factors. RESULTS: A total of 137,714 patients were screened, of whom 16,912 individuals (mean age: 61.5 years, men: 67.1%) were successfully enrolled. Among the enrolled participants, 4669 received the combined treatment of nicorandil and BBs, while 12,243 received BBs alone. After IPTW, the results demonstrated that the combined treatment was associated with a significantly reduced incidence of MACE (hazard ratio [HR] 0.79, 95% conidence interval [CI] 0.72-0.87) and stroke (HR 0.48, 95% CI 0.42-0.54) but not of MI (HR 1.03, 95% CI 0.92-1.15) or all-cause mortality (HR 0.93, 95% CI 0.64-1.37). Sensitivity analyses revealed similar results. CONCLUSIONS: A combined antiangina treatment of nicorandil and BBs may be more effective than treatment of BBs alone in reducing the long-term incidence of MACE in patients with CAD.

11.
Artigo em Inglês | MEDLINE | ID: mdl-37661869

RESUMO

BACKGROUND: In adults with type 2 diabetes (T2DM), sarcopenia and obesity are two common body composition issues. OBJECTIVE: We investigated the associated influencing factors of muscle mass loss in obese adults with T2DM, to provide a theoretical basis for the prevention of sarcopenic obesity in patients with T2DM. METHODS: We recruited 315 participants in this study. The participants underwent body composition assessment and clinical information was collected. Dual-energy X-ray absorptiometry was used to verify the accuracy of the body composition data. Based on their body fat percentage, 189 patients with T2DM were classified as obese. Patients with T2DM and obesity were grouped into the muscle mass loss group and non-muscle mass loss group based on gender. We collected demographic and clinical information about patients with T2DM who were obese, including their age, gender, body mass index (BMI), appendicular skeletal muscle index (ASMI), and body fat percentage (PBF). RESULTS: Among the participants who were obese and had T2DM, 56.61% (107/189) experienced muscle mass loss, with a detection rate of 43.42% (33/76) among females and 65.49% (74/113) among males. Body mass index, fat index, Android fat, Gynoid fat, limb fat, trunk fat, and total body bone mineral content were all lower in the muscle mass loss group compared to the non-muscle mass loss group, regardless of gender (all P< 0.001). Muscle mass loss in obese adults with T2DM was affected by BMI, body fat index, and limb fat. CONCLUSION: Muscle mass loss is more prevalent in adults with T2DM and a high PBF. Body mass index, body fat index, and limb fat are the protective factors of muscle mass loss in adult patients with T2DM and obesity.

12.
Adv Clin Exp Med ; 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37665083

RESUMO

Postoperative urinary retention (POUR) is a common surgical complication that can result in bladder overdistension, urinary tract infection and an extended hospital stay. Although neostigmine is an effective therapy for POUR, its usage remains controversial. The purpose of this study was to investigate the effectiveness of neostigmine in improving POUR after surgery. PubMed, Embase, Web of Science, and the Cochrane Library databases were reviewed. A methodical search approach was used for data extraction, while meta-analysis and bias analysis employed Review Manager 5.2 and MedCalc. Fourteen studies involving 4196 postoperative patients were included. With an odds ratio (OR) of 1.70, 95% confidence interval (95% CI) of 1.11-2.60 and an overall effect with p < 0.05, our analysis indicated that the patients receiving neostigmine had a greater effective urine retention rate than after other standard therapies. The subgroup analysis showed that neostigmine recipients had reduced residual urine volume (mean difference (MD) = -1.16, 95% CI: -2.05--0.27, overall p < 0.05, and I2 = 90%) and POUR (standardized MD (SMD) = 3.76, 95% CI: 2.19-5.34, overall p < 0.001, and I2 = 99% using a random effects model) as compared to controls. A random-effects model was utilized due to the substantial heterogeneity between trials. The studies were consistent and had no publication bias. Based on the findings of this meta-analysis, neostigmine can be considered an effective POUR treatment.

13.
Materials (Basel) ; 16(17)2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37687755

RESUMO

The process parameters of electrodeposited Ni-Fe-graphene composite coating on the 7075 aluminum alloy were optimized by the orthogonal experiment. The optimized process parameters were determined as follows: graphene concentration of 1 g L-1, current density of 9 A dm-2, agitation speed of 250 r min-1, and temperature of 60 °C, on the basis of hardness and friction coefficient. The Ni-Fe-graphene composite coating shows an increment of 393.0% in hardness and a decrement of 55.9% in friction coefficient in comparison with 7075 aluminum alloy substrate. The Ni-Fe-graphene composite coating binds tightly to 7075 aluminum alloy with adhesion strength of higher than 6.895 MPa. These make contributions to provide effective protection for aluminum alloys. Surface morphology and corrosion morphology, as well as morphology of the side bound to the substrate, were characterized. The scattered asperities on the surface were proven to be graphene nanoplatelets being wrapped by Ni-Fe, which comprehensively reveals the formation of asperities.

14.
Pest Manag Sci ; 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37671482

RESUMO

BACKGROUND: As maize is one of the world's most important crops, its stable production and supply is crucial for food security and socio-economic development. The cotton bollworm, Helicoverpa armigera (Hübner), is one of the major pests in maize. We evaluated the control effect of a bio-bait, an adult attractant, combined with insecticide, a 'toxicant-infused bait', on H. armigera populations in maize fields, as well as the impact on crop yield and quality through large-scale field applications in Hebei Province, China over a period spanning 2019 to 2021. RESULT: The number of male and female H. armigera adults killed by strip application ranged from 1 to 37 and 4 to 36 per strip, respectively, of which female moths were 53%. Following the application of toxicant-infused bait, we observed a significant reduction in the populations of eggs and larvae, with the average adjusted decrease range from 58% to 63% for eggs and 34% to 62% for larvae. The application of toxicant-infused bait also resulted in a notable reduction in the proportion of damaged maize plants, with an adjusted decline rate ranging from 59% to 69%. Concurrently, we observed an increase in yield by 4% to 8%. The concentration of aflatoxin in harvested maize grains was significantly reduced from an initial level of 1.24 ug/kg to 0.1 ug/kg. CONCLUSION: By applying toxicant-infused bait, there was a significant reduction in the population of H. armigera adults and their offspring, resulting in an improved yield and quality of maize. Toxicant-infused bait has great application potential in the integrated pest management of H. armigera. This article is protected by copyright. All rights reserved.

15.
Huan Jing Ke Xue ; 44(8): 4271-4278, 2023 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-37694622

RESUMO

The current regulatory site investigation employs the J&E model to predict vapor intrusion risk. However, the J&E model assumes that the source concentration is constant for a given exposure period, which is not consistent with the actual site source under depletion. In this study, we compared the differences between the J&E model (constant source), SD source depletion model, and RBCA source depletion model for predicting indoor concentration variation as well as the risk levels during the exposure period with a case study in Beijing. The results showed that the source and indoor air concentrations predicted by the SD and RBCA models showed exponential decreases, whereas those predicted by the J&E model maintained high concentrations throughout the exposure period, which greatly overestimated the risk. The RBCA predicted source depletion at the fastest rate, but the predicted indoor air concentrations were still lower than those of the SD model, which was related to the fact that the RBCA did not consider the effect of buildings on source depletion and did not follow mass conservation. Further, the sensitivity analysis showed that the pressure difference (dP) had the greatest influence on the source concentration in the SD model. For the calculated carcinogenic risk and hazard quotients, the J&E constant source model, the SD source depletion model, and the RBCA source depletion model were ranked in descending order. The results indicated that in general the J&E model was too conservative, the RBCA model may have underestimated risk, and the SD model was more suitable for quantifying vapor intrusion risk in reality.

16.
Curr Med Chem ; 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37694790

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) is a major type of lung cancer worldwide, and under the pandemic coronavirus disease 2019 (COVID-19), its cancer burden is enlarged. This study aimed to explore potential drug targets and potential drugs for developing effective treatments for patients with both lung cancer and COVID-19. METHOD: The interaction network of molecule compounds-target genes was constructed based on Traditional Chinese Medicines (TCMs) and gene expression data from public databases. The potential effectiveness of drugs was analyzed by molecular docking and molecular dynamics simulation. Western blot, transfection assay, Immunohistochemistry (IHC) staining, and flow cytometry were performed to investigate the function of HSP90AA1 in LUAD cells. RESULT: Eight target genes (GSK3B, HMOX1, HSP90AA1, ICAM1, MAPK1, PLAU, RELA and TNFSF15.) were identified, and two of them (HSP90AA1 and RELA) were significantly associated with LUAD prognosis. Luteolin was discovered to bind with HSP90AA1. Moreover, In vitro cell experiments demonstrated that HSP90AA1 had higher expression in A549 cells, promoted cell viability and suppressed apoptosis in A549 cells and H1299 cells. CONCLUSION: HSP90AA1 was a target gene for further designing effective drugs for LUAD patients. Luteolin was a potential drug for treating patients with both LUAD and COVID-19.

17.
Food Chem ; 434: 137354, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37696157

RESUMO

A novel extraction adsorbent composite of MWCNTs/NH2-MIL-101(Fe) was synthesized, and was used to extract 6 kinds of neonicotinoid pesticides in medicine and food homology products. The composite was characterized by scanning electron microscope (SEM), fourier transform-infrared (FT-IR) spectroscopy, and X-ray powder diffraction (XRD). MWCNTs were enveloped around MOFs to provide physical support for the crystal structure. The adsorbent has higher adsorption capacity and reusability than pure NH2-MIL-101(Fe). Combined with UPLC-MS/MS, the method showed the low limit of detection (LOD) and limit of quantitation (LOQ) of 0.01-0.07 µg/kg and 0.04-0.22 µg/kg, respectively. It exhibited high extraction recovery of 77.86-101.10% for neonicotinoid pesticides in spiked samples. Meanwhile, this novel method could be successfully employed for the detection of other medicine and food homology products. Compared with previous reports, this method has advantages in detection limit and extraction recovery, indicating that it can be a preferential choice for the detection of neonicotinoid pesticides.

19.
Acta Pharmacol Sin ; 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37696989

RESUMO

Kidney fibrosis is the hallmark of chronic kidney disease (CKD) progression, whereas no effective anti-fibrotic therapies exist. Recent evidence has shown that tubular ferroptosis contributes to the pathogenesis of CKD with persistent proinflammatory and profibrotic responses. We previously reported that natural flavonol fisetin alleviated septic acute kidney injury and protected against hyperuricemic nephropathy in mice. In this study, we investigated the therapeutic effects of fisetin against fibrotic kidney disease and the underlying mechanisms. We established adenine diet-induced and unilateral ureteral obstruction (UUO)-induced CKD models in adult male mice. The two types of mice were administered fisetin (50 or 100 mg·kg-1·d-1, i.g.) for 3 weeks or 7 days, respectively. At the end of the experiments, the mice were euthanized, and blood and kidneys were gathered for analyzes. We showed that fisetin administration significantly ameliorated tubular injury, inflammation, and tubulointerstitial fibrosis in the two types of CKD mice. In mouse renal tubular epithelial (TCMK-1) cells, treatment with fisetin (20 µM) significantly suppressed adenine- or TGF-ß1-induced inflammatory responses and fibrogenesis, and improved cell viability. By quantitative real-time PCR analysis of ferroptosis-related genes, we demonstrated that fisetin treatment inhibited ferroptosis in the kidneys of CKD mice as well as in injured TCMK-1 cells, as evidenced by decreased ACSL4, COX2, and HMGB1, and increased GPX4. Fisetin treatment effectively restored ultrastructural abnormalities of mitochondrial morphology and restored the elevated iron, the reduced GSH and GSH/GSSG as well as the increased lipid peroxide MDA in the kidneys of CKD mice. Notably, abnormally high expression of the ferroptosis key marker ACSL4 was verified in the renal tubules of CKD patients (IgAN, MN, FSGS, LN, and DN) as well as adenine- or UUO-induced CKD mice, and in injured TCMK-1 cells. In adenine- and TGF-ß1-treated TCMK-1 cells, ACSL4 knockdown inhibited tubular ferroptosis, while ACSL4 overexpression blocked the anti-ferroptotic effect of fisetin and reversed the cytoprotective, anti-inflammatory, and anti-fibrotic effects of fisetin. In summary, we reveal a novel aspect of the nephroprotective effect of fisetin, i.e. inhibiting ACSL4-mediated tubular ferroptosis against fibrotic kidney diseases.

20.
Mol Neurobiol ; 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37697219

RESUMO

Diabetes-associated cognitive dysfunction (DACD) is considered a significant complication of diabetes and manifests as cognitive impairment. Astrocytes are vital to the brain energy metabolism and cerebral antioxidant status. Ferroptosis has been implicated in cognitive impairment, but it is unclear whether the ferroptosis of astrocytes is involved in the progression of DACD. PPARA/PPARα (peroxisome proliferator-activated receptor alpha) is a transcription factor that regulates glucose and lipid metabolism in the brain. In this study, we demonstrated that high glucose promoted ferroptosis of astrocytes by disrupting iron metabolism and suppressing the xCT/GPX4-regulated pathway in diabetic mice and astrocytes cultured in high glucose. Administration of gemfibrozil, a known PPARα agonist, inhibited ferroptosis and improved memory impairment in db/db mice. Gemfibrozil also prevented the accumulation of lipid peroxidation products and lethal reactive oxygen species induced by iron deposition in astrocytes and substantially reduced neuronal and synaptic loss. Our findings demonstrated that ferroptosis of astrocytes is a novel mechanism in the development of DACD. Additionally, our study revealed the therapeutic effect of gemfibrozil in preventing and treating DACD by inhibiting ferroptosis.

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