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1.
Ecotoxicol Environ Saf ; 281: 116661, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38954907

RESUMEN

OBJECTIVE: Baicalin has antioxidative, antiviral, and anti-inflammatory properties. However, its ability to alleviate oxidative stress (OS) and DNA damage in liver cells exposed to aflatoxin B1 (AFB1), a highly hepatotoxic compound, remains uncertain. In this study, the protective effects of baicalin on AFB1-induced hepatocyte injury and the mechanisms underlying those effects were investigated. METHODS: Stable cell lines expressing CYP3A4 were established using lentiviral vectors to assess oxidative stress levels by conducting assays to determine the content of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Additionally, DNA damage was evaluated by 8-hydroxy-2-deoxyguanosine (8-OHdG) and comet assays. Transcriptome sequencing, molecular docking, and in vitro experiments were conducted to determine the mechanisms underlying the effects of baicalin on AFB1-induced hepatocyte injury. In vivo, a rat model of hepatocyte injury induced by AFB1 was used to evaluate the effects of baicalin. RESULTS: In vitro, baicalin significantly attenuated AFB1-induced injury caused due to OS, as determined by a decrease in ROS, MDA, and SOD levels. Baicalin also considerably decreased AFB1-induced DNA damage in hepatocytes. This protective effect of baicalin was found to be closely associated with the TP53-mediated ferroptosis pathway. To elaborate, baicalin physically interacts with P53, leading to the suppression of the expression of GPX4 and SLC7A11, which in turn inhibits ferroptosis. In vivo findings showed that baicalin decreased DNA damage and ferroptosis in AFB1-treated rat liver tissues, as determined by a decrease in the expression of γ-H2AX and an increase in GPX4 and SLC7A11 levels. Overexpression of TP53 weakened the protective effects of baicalin. CONCLUSIONS: Baicalin can alleviate AFB1-induced OS and DNA damage in liver cells via the TP53-mediated ferroptosis pathway. In this study, a theoretical foundation was established for the use of baicalin in protecting the liver from the toxic effects of AFB1.

2.
J Asian Nat Prod Res ; : 1-9, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38900048

RESUMEN

A new coumarin (1) and a new flavonoid (2) were isolated from the air-dried flower buds of Ochrocarpus longifolius, together with ten known compounds (3-12). The structures of two new compounds were established by 1D and 2D NMR and MS data. In addition, the new compound 2 showed significant proliferation inhibitory activity on Eca-109 and MGC-803 cells. The results of this study may enrich the diversity of compounds from O. longifolius and provide a basis for further research on its natural products and pharmacological activities.

3.
Biochem Pharmacol ; 226: 116344, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38852647

RESUMEN

Antimicrobial peptides (AMPs) are an important component of innate immunity in both vertebrates and invertebrates, and some of the unique characteristics of AMPs are usually associated with their living environment. The marine fish, mudskipper Boleophthalmus pectinirostris, usually live amphibiously in intertidal environments that are quite different from other fish species, which would be an exceptional source of new AMPs. In the study, an AMP named Bolespleenin334-347 was identified, which was a truncated peptide derived from a new functional gene found in B. pectinirostris, that was up-regulated in response to bacterial challenge. Bolespleenin334-347 had only 14 amino acid residues, including five consecutive arginine residues. It was found that the peptide had broad-spectrum antibacterial activity, good thermal stability and sodium ion tolerance. Bolespleenin334-347 killed Acinetobacter baumannii and Staphylococcus aureus by disrupting the structural integrity of the bacterial membrane, leading to leakage of the cellular contents, and inducing accumulation of bacterial endogenous reactive oxygen species (ROS). In addition, Bolespleenin334-347 effectively inhibited biofilm formation of A. baumannii and S. aureus and long-term treatment did not lead to the development of resistance. Importantly, Bolespleenin334-347 maintained stable activity against clinically multi-drug resistant bacterial strains. In addition, it was noteworthy that Bolespleenin334-347 showed superior efficacy to LL-37 and vancomycin in a constructed mouse model of MRSA-induced superficial skin infections, as evidenced by a significant reduction in bacterial load and more favorable wound healing. This study provides an effective antimicrobial agent for topical skin infections with potential therapeutic efficacy for infections with drug-resistant bacteria, including MRSA.

4.
Exp Neurol ; 379: 114849, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38857748

RESUMEN

Cerebral ischemic stroke is a serious disease with high mortality and disability rates. However, few neuroprotective drugs have been used for ischemic stroke in the clinic. Two main reasons may be responsible for this failure: difficulty in penetrating the blood-brain barrier (BBB) and easily inactivated in the blood circulation. Ferroptosis, a lipid oxidation-related cell death, plays significant roles in cerebral ischemia-reperfusion injury. We utilized RVG29, a peptide derived from Rabies virus glycoprotein, to obtain BBB-targeted lipid nanoparticles (T-LNPs) in order to investigate whether T-LNPs improved the neuroprotective effects of Ferrostatin-1 (Fer1, an inhibitor of ferroptosis) against cerebral ischemic damage. T-LNPs significantly increased BBB penetration following oxygen/glucose deprivation exposure in an in vitro BBB model and enhanced the fluorescence distribution in brain tissues at 6 h post-administration in a cerebral ischemic murine model. Moreover, T-LNPs encapsulated Fer1 (T-LNPs-Fer1) significantly enhanced the inhibitory effects of Fer1 on ferroptosis by maintaining the homeostasis of NADPH oxidase 4 (NOX4) and glutathione peroxidase 4 (GPX4) signals in neuronal cells after cerebral ischemia. T-LNPs-Fer1 significantly suppressed oxidative stress [heme oxygenase-1 expression and malondialdehyde (the product of lipid ROS reaction)] in neurons and alleviated ischemia-induced neuronal cell death, compared to Fer1 alone without encapsulation. Furthermore, T-LNPs-Fer1 significantly reduced cerebral infarction and improved behavior functions compared to Fer1-treated cerebral ischemic mice after 45-min ischemia/24-h reperfusion. These findings showed that the T-LNPs helped Fer1 penetrate the BBB and improved the neuroprotection of Fer1 against cerebral ischemic damage in experimental stroke, providing a feasible translational strategy for the development of clinical drugs for the treatment of ischemic stroke.

5.
Orthop Surg ; 16(7): 1648-1656, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38778391

RESUMEN

OBJECTIVE: Percutaneous repair is an alternative to open surgical repair of the Achilles tendon with comparable, functional results and low re-rupture and infection rates; however, sural nerve injury is a known complication. The purpose of this study is to design a new surgical procedure, the minimally invasive peritendinous submembrane access technique (MIS-PSAT). It offers optimal results, with excellent functional outcomes, and with minimal soft tissue complications and sural nerve injury. METHODS: This retrospective study included 249 patients with acute closed Achilles tendon ruptures treated at our institution between 2009 and 2019. All patients underwent MIS-PSAT at our institution and were followed up for 8-48 months. Functional evaluation was based on the Achilles tendon total rupture score (ATRS) and the American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS-AHS), associated with local complications and isokinetic tests. RESULTS: None of the patients had infection, necrosis, or sural nerve injury. Re-rupture occurred in two cases. The average times to return to work and sports was 10.4 and 31.6 weeks, respectively. The average ATRS and AOFAS-AHS scores were 90.2 and 95.7, respectively, with an excellent rate of 99.5%. Isokinetic tests showed that ankle function on the affected side was comparable with that on the healthy side (p > 0.05). CONCLUSION: The MIS-PSAT for acute Achilles tendon rupture is easy to perform with few complications. Importantly, the surgical technique reduces the risk of sural nerve injuries. Patients have high postoperative satisfaction, low re-rupture rates, and muscle strength, and endurance can be restored to levels similar to those on the healthy side.


Asunto(s)
Tendón Calcáneo , Procedimientos Quirúrgicos Mínimamente Invasivos , Traumatismos de los Tendones , Humanos , Tendón Calcáneo/lesiones , Tendón Calcáneo/cirugía , Estudios Retrospectivos , Rotura/cirugía , Masculino , Femenino , Adulto , Persona de Mediana Edad , Traumatismos de los Tendones/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Adulto Joven , Anciano
7.
Toxicol Appl Pharmacol ; 486: 116935, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38648938

RESUMEN

Metal exposure is linked to numerous pathological outcomes including cancer, cardiovascular disease, and diabetes. Over the past decades, we have made significant progress in our understanding of how metals are linked to disease, but there is still much to learn. In October 2022, experts studying the consequences of metal exposures met in Montréal, Québec, to discuss recent advances and knowledge gaps for future research. Here, we present a summary of presentations and discussions had at the meeting.


Asunto(s)
Metales , Neoplasias , Humanos , Neoplasias/inducido químicamente , Animales , Metales/toxicidad , Carcinogénesis/inducido químicamente , Carcinogénesis/efectos de los fármacos
8.
Angew Chem Int Ed Engl ; 63(27): e202403264, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38659076

RESUMEN

In situ cyclized polyacrylonitrile (CPAN) is developed to replace n-type metal oxide semiconductors (TiO2 or SnO2) as an electron selective layer (ESL) for highly efficient and stable n-i-p perovskite solar cells (PSCs). The CPAN layer is fabricated via facile in situ cyclization reaction of polyacrylonitrile (PAN) coated on a conducting glass substrate. The CPAN layer is robust and insoluble in common solvents, and possesses n-type semiconductor properties with a high electron mobility of 4.13×10-3 cm2 V-1 s-1. With the CPAN as an ESL, the PSC affords a power conversion efficiency (PCE) of 23.12 %, which is the highest for the n-i-p PSCs with organic ESLs. Moreover, the device with the CPAN layer holds superior operational stability, maintaining over 90 % of their initial efficiency after 500 h continuous light soaking. These results confirm that the CPAN layer would be a desirable low-cost and efficient ESL for n-i-p PSCs and other photoelectronic devices with high performance and stability.

9.
Sci Rep ; 14(1): 9317, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38653748

RESUMEN

Carbon fibre-reinforced polymer (CFRP) plates can efficiently repair or enhance the mechanical properties of the square hollow section. However, the loading end of such a CFRP-strengthened member is prone to local bearing failure under compressive load. Given this limitation, an innovative CFRP-plate-strengthened square hollow section composite member (CFRP-SHSCM) was raised, and the thick-walled section was welded on both ends of the thin-walled steel column. The mechanical properties of CFRP-SHSCMs were investigated through parameter finite element (FE) analysis, focusing on the influence of the amount of CFRP layers (nc), the slenderness ratio (λ), the initial geometric imperfections (v0), the CFRP layouts (2S and 4S) and the length of the exposed steel column (Le). The load-displacement curves, the bearing force, and typical failure modes were also acquired. Results indicated that with increasing nc and v0, and decreasing λ, the conventional CFRP-SHSCMs were prone to local bearing failure with poor ductility, leading to the insufficient use of the CFRP plate, in contrast, the improved CFRP-SHSCMs primarily underwent overall buckling failure and exhibited better bearing force and ductility. Finally, the modified Perry-Robertson formula was put forward to predict the ultimate load of the CFRP-SHSCMs. The coefficients of variation between the FE simulation and the theoretical results were 0.00436 and 0.0292, respectively.

10.
Zhongguo Zhong Yao Za Zhi ; 49(4): 951-960, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38621902

RESUMEN

The chemical constituents of ethyl acetate from Hypericum himalaicum were isolated by silica gel column chromatography, gel column chromatography, and high-performance liquid chromatography. The structure of the isolated compounds was identified by modern spectral techniques(NMR, MS, IR, and UV), and the potential anti-inflammatory targets and action pathways were analyzed and predicted by network pharmacology and molecular docking methods.Ten compounds were isolated from H. himalaicum and identified as 5,9,11-trihydroxy-3,3-dimethyl-3H,8H-benzo[6,7][1,4]dioxepino[2,3-f]chromen-8-one(1), betulinic acid(2), demethyltorosaflavone C(3), kaempferol(4), quercetin(5), hyperwightin B(6), toxyloxanthone B(7), 1,7-dihydroxy-xanthone(8), emodin(9), and 1,7-dihydroxy-4-methoxy-xanthone(10). Among them, compound 1 was a new compound, and compounds 2-10 were isolated from H. himalaicum for the first time. Network pharmacology screened 60 key anti-inflammatory targets. By acting on TNF, AKT1, CASP3, and other key targets, involving PI3K-AKT signaling pathway, IL-17 signaling pathway, VEGF signaling pathway, MAPK signaling pathway, and other signaling pathways, and phosphorylation, cell migration and movement, protein tyrosine kinase, and other biological processes were regulated to achieve anti-inflammatory effects. The results of molecular docking show that the above components have good binding properties with the core targets.


Asunto(s)
Medicamentos Herbarios Chinos , Hypericum , Xantonas , Farmacología en Red , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas , Antiinflamatorios/farmacología , Proteínas Proto-Oncogénicas c-akt
11.
Anal Chem ; 96(14): 5580-5588, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38532617

RESUMEN

Herein, a novel strategy was implemented to modulate the supramolecular interaction between enantiomers and chiral recognition sites (CRSs), effectively resolving the issue of CRS saturation. Randomly methylated-ß-cyclodextrin (Rm-ß-CD) was used as the CRS (host molecule), and polymerized ionic liquids [poly([vbim]TFSI)] were used as the supramolecular modulator (guest molecule), which self-assembled to generate thermosensitive supramolecular host/guest complexes. The enantiomeric binding capacity and enantioselectivity of chiral separation systems centered on supramolecular host-guest complexes are characterized by a high degree of temperature dependence. Poly([vbim]TFSI) bonded to Rm-ß-CD at temperatures between 17 °C ± 3 and 50 °C ± 3 °C, and the binding free energy difference (|ΔΔG|) between the (S)- and (R)-enantiomer was 0.55. Conversely, poly([vbim]TFSI detached from Rm-ß-CD at temperatures >50 °C ± 3 °C or <17 °C ± 3 °C, and |ΔΔG| between (S)- and (R)-enantiomer was 0.03. The |ΔΔG| value of the (R)-enantiomer can reach 0.86 in two temperature intervals. Therefore, the binding of poly([vbim]TFSI) to Rm-ß-CD afforded the favorable separation of four racemic sample mixtures: mandelic acid (e.e.% = 61.3%), ibuprofen (e.e.% = 21.6%), warfarin (e.e.% = 14.9%), and naproxen (e.e% = 18.2%). The detachment of poly([vbim]TFSI) from Rm-ß-CD released the enantiomer bound to CRSs. The decomplexation of mandelic acid reached 75.1%.

12.
Plant Methods ; 20(1): 48, 2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38521920

RESUMEN

BACKGROUND: Leaf water content (LWC) significantly affects rice growth and development. Real-time monitoring of rice leaf water status is essential to obtain high yield and water use efficiency of rice plants with precise irrigation regimes in rice fields. Hyperspectral remote sensing technology is widely used in monitoring crop water status because of its rapid, nondestructive, and real-time characteristics. Recently, multi-source data have been attempted to integrate into a monitored model of crop water status based on spectral indices. However, there are fewer studies using spectral index model coupled with multi-source data for monitoring LWC in rice plants. Therefore, 2-year field experiments were conducted with three irrigation regimes using four rice cultivars in this study. The multi-source data, including canopy ecological factors and physiological parameters, were incorporated into the vegetation index to accurately predict LWC in rice plants. RESULTS: The results presented that the model accuracy of rice LWC estimation after combining data from multiple sources improved by 6-44% compared to the accuracy of a single spectral index normalized difference index (ND). Additionally, the optimal prediction accuracy of rice LWC was produced using a machine algorithm of gradient boosted decision tree (GBDT) based on the combination of ND(1287,1673) and crop water stress index (CWSI) (R2 = 0.86, RMSE = 0.01). CONCLUSIONS: The machine learning estimation model constructed based on multi-source data fully utilizes the spectral information and considers the environmental changes in the crop canopy after introducing multi-source data parameters, thus improving the performance of spectral technology for monitoring rice LWC. The findings may be helpful to the water status diagnosis and accurate irrigation management of rice plants.

13.
Heliyon ; 10(2): e25052, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38312551

RESUMEN

Background: and Purpose: Hemorrhagic transformation (HT) is one of the severe complications in acute ischemic stroke, especially for the patients who undergo recanalization treatment. It is crucial to screen patients who have high risk of HT before recanalization. However, current prediction models based on clinical factors are not ideal for clinical practice. Serum occludin, a biomarker for cerebral ischemia-induced blood-brain barrier disruption, has potential for predicting HT. This study was to investigate whether the combination of serum occludin and clinical risk factors improved the efficacy of predicting HT. Methods: This was a single-center prospective observational study. Baseline clinical data and blood samples of recanalization patients were collected upon admission to our hospital. The level of serum occludin was measured using enzyme-linked immunosorbent assay. The diagnosis of HT was confirmed by CT scans within 36 h post recanalization. Results: A total of 324 patients with recanalization were enrolled and 68 patients presented HT occurrence. HT patients had the higher level of baseline occludin than patients without HT (p < 0.001). Multivariate regression analysis showed that serum occludin level, Alberta Stroke Program Early CT Scores and endovascular therapy were independent risk factors (p < 0.05) for HT after adjusting potential confounders. The combination of serum occludin and clinical risk factors significantly improved the accuracy of predicting HT [area under the curve (AUC, 0.821 vs 0.701, p < 0.001), and net reclassification improvement (31.1 %), integrated discrimination improvement (21.5 %), p < 0.001] compared to a model employing only clinical risk factors. The modified AUC (0.806) of combined model based on 10-fold-cross-validation was still higher than clinical risk model (0.701). Conclusion: The combination of serum occludin and clinical risk factors significantly improved the prediction efficacy for HT, providing a novel potential prediction model to screen for patients with high risk of HT before recanalization in acute ischemic stroke.

14.
Toxicol Appl Pharmacol ; 484: 116858, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38341105

RESUMEN

Chronic arsenic exposures are associated with multiple hematologic disturbances, including anemia. The goal of this study was to evaluate associations between arsenic exposures and hematological parameters among men and women who are chronically exposed to elevated levels of arsenic from drinking water. Hematologic analyses were performed on blood collected from 755 participants (45% male and 54% female) in the Health Effects of Arsenic Longitudinal Study (HEALS) cohort, Bangladesh. Herein, we used linear regression models to estimate associations between red blood cell (RBC) parameters (i.e., RBC counts, hematocrit (HCT), hemoglobin (Hgb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC)) and measurements of arsenic exposure (urinary arsenic and urinary arsenic metabolites). Arsenic exposures showed trending associations with decreased RBC counts in both men and women, a positive association with MCV in males, and an inverse association with MCHC among males, but not among non-smoking females. Among men, those who smoked had stronger associations between arsenic exposures and MCHC than non-smoking males. Collectively, our results show that arsenic exposures affect multiple RBC parameters and highlight potentially important sex differences in arsenic-induced hematotoxicity.


Asunto(s)
Arsénico , Adulto , Femenino , Humanos , Masculino , Arsénico/toxicidad , Estudios Longitudinales , Bangladesh/epidemiología , Eritrocitos , Índices de Eritrocitos
15.
Metallomics ; 16(3)2024 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-38419293

RESUMEN

Ischemic stroke is a leading cause of death and disability worldwide, and presently, there is no effective neuroprotective therapy. Zinc is an essential trace element that plays important physiological roles in the central nervous system. Free zinc concentration is tightly regulated by zinc-related proteins in the brain under normal conditions. Disruption of zinc homeostasis, however, has been found to play an important role in the mechanism of brain injury following ischemic stroke. A large of free zinc releases from storage sites after cerebral ischemia, which affects the functions and survival of nerve cells, including neurons, astrocytes, and microglia, resulting in cell death. Ischemia-triggered intracellular zinc accumulation also disrupts the function of blood-brain barrier via increasing its permeability, impairing endothelial cell function, and altering tight junction levels. Oxidative stress and neuroinflammation have been reported to be as major pathological mechanisms in cerebral ischemia/reperfusion injury. Studies have showed that the accumulation of intracellular free zinc could impair mitochondrial function to result in oxidative stress, and form a positive feedback loop between zinc accumulation and reactive oxygen species production, which leads to a series of harmful reactions. Meanwhile, elevated intracellular zinc leads to neuroinflammation. Recent studies also showed that autophagy is one of the important mechanisms of zinc toxicity after ischemic injury. Interrupting the accumulation of zinc will reduce cerebral ischemia injury and improve neurological outcomes. This review summarizes the role of zinc toxicity in cellular and tissue damage following cerebral ischemia, focusing on the mechanisms about oxidative stress, inflammation, and autophagy.


Asunto(s)
Lesiones Encefálicas , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Daño por Reperfusión , Humanos , Zinc/metabolismo , Enfermedades Neuroinflamatorias , Estrés Oxidativo , Isquemia Encefálica/metabolismo , Barrera Hematoencefálica/metabolismo , Autofagia , Accidente Cerebrovascular Isquémico/metabolismo , Lesiones Encefálicas/metabolismo , Daño por Reperfusión/metabolismo
16.
PhytoKeys ; 237: 79-89, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38282985

RESUMEN

Aletrisguangxiensis Y. Nong & Y. F. Huang (Nartheciaceae), a new species from Guangxi, China, is described and illustrated. This new species is most similar to A.scopulorum, but it can be easily distinguished by its sparsely glandular, 5-18 cm long scape, glandular inflorescence axis, distinctly pedicellate flowers, sparsely glandular, 5-10 mm long pedicel, bract borne at base of pedicel, glabrous perianth divided to the base, strongly recurved or revolute perianth lobes and turbinate, obovoid to oblong-obovoid capsule. An identification key for 24 species and 1 hybrid of Aletris is also provided.

17.
Proc Natl Acad Sci U S A ; 121(4): e2310854121, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38241433

RESUMEN

Noncoding mutation hotspots have been identified in melanoma and many of them occur at the binding sites of E26 transformation-specific (ETS) proteins; however, their formation mechanism and functional impacts are not fully understood. Here, we used UV (Ultraviolet) damage sequencing data and analyzed cyclobutane pyrimidine dimer (CPD) formation, DNA repair, and CPD deamination in human cells at single-nucleotide resolution. Our data show prominent CPD hotspots immediately after UV irradiation at ETS binding sites, particularly at sites with a conserved TTCCGG motif, which correlate with mutation hotspots identified in cutaneous melanoma. Additionally, CPDs are repaired slower at ETS binding sites than in flanking DNA. Cytosine deamination in CPDs to uracil is suggested as an important step for UV mutagenesis. However, we found that CPD deamination is significantly suppressed at ETS binding sites, particularly for the CPD hotspot on the 5' side of the ETS motif, arguing against a role for CPD deamination in promoting ETS-associated UV mutations. Finally, we analyzed a subset of frequently mutated promoters, including the ribosomal protein genes RPL13A and RPS20, and found that mutations in the ETS motif can significantly reduce the promoter activity. Thus, our data identify high UV damage and low repair, but not CPD deamination, as the main mechanism for ETS-associated mutations in melanoma and uncover important roles of often-overlooked mutation hotspots in perturbing gene transcription.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/genética , Citosina , Desaminación , Neoplasias Cutáneas/genética , Mutación , Dímeros de Pirimidina , Sitios de Unión , Rayos Ultravioleta , Daño del ADN , Reparación del ADN/genética
18.
Free Radic Biol Med ; 212: 360-374, 2024 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-38171407

RESUMEN

Evidence recently showed that pleiotropic cytokine interferon-gamma (IFN-γ) in the tumor microenvironment (TME) plays a positive role in hepatocellular carcinoma (HCC) progression through the regulation of liver cancer stem cells (LCSCs) in HCC. The present study explored the role and potential mechanism of mitochondrial programmed cell death-ligand 1 (PD-L1) and its regulation of ferroptosis in modulating the cancer stemness of LCSCs. It was shown that mimicking TME IFN-γ exposure increased the LCSCs ratio and cancer stemness phenotypes in HCC cells. IFN-γ exposure inhibited sorafenib (Sora)-induced ferroptosis by enhancing glutathione peroxidase 4 (GPX4) expression as well reactive oxygen species (ROS) and lipid peroxidation (LPO) generation in LCSCs. Furthermore, IFN-γ exposure upregulated PD-L1 expression and its mitochondrial translocation, inducing dynamin-related protein 1 (Drp1)-dependent mitochondrial fission and correlating with glycolytic metabolism reprogramming in LCSCs. The genetic intervention of PD-L1 promoted ferroptosis-dependent anti-tumor effects of Sora, reduced glycolytic metabolism reprogramming, and inhibited cancer stemness of HCC in vitro and in vivo. Our results revealed a novel mechanism that IFN-γ exposure-induced mitochondrial translocation of PD-L1 enhanced glycolytic reprogramming to mediate the GPX4-dependent ferroptosis resistance and cancer stemness in LCSCs. This study provided new insights into the role of mitochondrial PD-L1-Drp1-GPX4 signal axis in regulating IFN-γ exposure-associated cancer stemness in LCSCs and verified that PD-L1-targeted intervention in combination with Sora might achieve promising synergistic anti-HCC effects.


Asunto(s)
Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Sorafenib/farmacología , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Interferón gamma/genética , Interferón gamma/metabolismo , Ferroptosis/genética , Línea Celular Tumoral , Microambiente Tumoral
20.
J Integr Plant Biol ; 66(4): 660-682, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37968901

RESUMEN

Due to its tropical origins, rice (Oryza sativa) is susceptible to cold stress, which poses severe threats to production. OsNAC5, a NAC-type transcription factor, participates in the cold stress response of rice, but the detailed mechanisms remain poorly understood. Here, we demonstrate that OsNAC5 positively regulates cold tolerance at germination and in seedlings by directly activating the expression of ABSCISIC ACID INSENSITIVE 5 (OsABI5). Haplotype analysis indicated that single nucleotide polymorphisms in a NAC-binding site in the OsABI5 promoter are strongly associated with cold tolerance. OsNAC5 also enhanced OsABI5 stability, thus regulating the expression of cold-responsive (COR) genes, enabling fine-tuned control of OsABI5 action for rapid, precise plant responses to cold stress. DNA affinity purification sequencing coupled with transcriptome deep sequencing identified several OsABI5 target genes involved in COR expression, including DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR 1A (OsDREB1A), OsMYB20, and PEROXIDASE 70 (OsPRX70). In vivo and in vitro analyses suggested that OsABI5 positively regulates COR gene transcription, with marked COR upregulation in OsNAC5-overexpressing lines and downregulation in osnac5 and/or osabi5 knockout mutants. This study extends our understanding of cold tolerance regulation via OsNAC5 through the OsABI5-CORs transcription module, which may be used to ameliorate cold tolerance in rice via advanced breeding.


Asunto(s)
Oryza , Oryza/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Proteínas de Plantas/metabolismo , Fitomejoramiento , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ácido Abscísico/farmacología , Ácido Abscísico/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Frío
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