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1.
bioRxiv ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38585933

RESUMO

Prime editing installs precise edits into the genome with minimal unwanted byproducts, but low and variable editing efficiencies have complicated application of the approach to high-throughput functional genomics. Leveraging several recent advances, we assembled a prime editing platform capable of high-efficiency substitution editing across a set of engineered prime editing guide RNAs (epegRNAs) and corresponding target sequences (80% median intended editing). Then, using a custom library of 240,000 epegRNAs targeting >17,000 codons with 175 different substitution types, we benchmarked our platform for functional interrogation of small substitution variants (1-3 nucleotides) targeted to essential genes. Resulting data identified negative growth phenotypes for nonsense mutations targeted to ∼8,000 codons, and comparing those phenotypes to results from controls demonstrated high specificity. We also observed phenotypes for synonymous mutations that disrupted splice site motifs at 3' exon boundaries. Altogether, we establish and benchmark a high-throughput prime editing approach for functional characterization of genetic variants with simple readouts from multiplexed experiments.

2.
Sci Rep ; 14(1): 8023, 2024 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580805

RESUMO

Toxic metals are vital risk factors affecting serum ion balance; however, the effect of their co-exposure on serum ions and the underlying mechanism remain unclear. We assessed the correlations of single metal and mixed metals with serum ion levels, and the mediating effects of mineralocorticoids by investigating toxic metal concentrations in the blood, as well as the levels of representative mineralocorticoids, such as deoxycorticosterone (DOC), and serum ions in 471 participants from the Dongdagou-Xinglong cohort. In the single-exposure model, sodium and chloride levels were positively correlated with arsenic, selenium, cadmium, and lead levels and negatively correlated with zinc levels, whereas potassium and iron levels and the anion gap were positively correlated with zinc levels and negatively correlated with selenium, cadmium and lead levels (all P < 0.05). Similar results were obtained in the mixed exposure models considering all metals, and the major contributions of cadmium, lead, arsenic, and selenium were highlighted. Significant dose-response relationships were detected between levels of serum DOC and toxic metals and serum ions. Mediation analysis showed that serum DOC partially mediated the relationship of metals (especially mixed metals) with serum iron and anion gap by 8.3% and 8.6%, respectively. These findings suggest that single and mixed metal exposure interferes with the homeostasis of serum mineralocorticoids, which is also related to altered serum ion levels. Furthermore, serum DOC may remarkably affect toxic metal-related serum ion disturbances, providing clues for further study of health risks associated with these toxic metals.


Assuntos
Arsênio , Metais Pesados , Selênio , Humanos , Chumbo/toxicidade , Arsênio/toxicidade , Cádmio/toxicidade , Análise de Mediação , Mineralocorticoides , Intoxicação por Metais Pesados , Zinco , Ferro , Íons , China , Metais Pesados/toxicidade
3.
Nature ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570691

RESUMO

Prime editing enables the precise modification of genomes through reverse transcription of template sequences appended to the 3' ends of CRISPR-Cas guide RNAs1. To identify cellular determinants of prime editing, we developed scalable prime editing reporters and performed genome-scale CRISPR-interference screens. From these screens, a single factor emerged as the strongest mediator of prime editing: the small RNA-binding exonuclease protection factor La. Further investigation revealed that La promotes prime editing across approaches (PE2, PE3, PE4 and PE5), edit types (substitutions, insertions and deletions), endogenous loci and cell types but has no consistent effect on genome-editing approaches that rely on standard, unextended guide RNAs. Previous work has shown that La binds polyuridine tracts at the 3' ends of RNA polymerase III transcripts2. We found that La functionally interacts with the 3' ends of polyuridylated prime editing guide RNAs (pegRNAs). Guided by these results, we developed a prime editor protein (PE7) fused to the RNA-binding, N-terminal domain of La. This editor improved prime editing with expressed pegRNAs and engineered pegRNAs (epegRNAs), as well as with synthetic pegRNAs optimized for La binding. Together, our results provide key insights into how prime editing components interact with the cellular environment and suggest general strategies for stabilizing exogenous small RNAs therein.

4.
Opt Express ; 32(7): 10829-10840, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38570946

RESUMO

Imaging of electronic device surface or sub-surface electromagnetic fields under operating conditions is important for device design and diagnosis. In this study, we proposed a method to characterize specific magnetic field properties of electromagnetic devices at micron-scale using a solid-state quantum sensor, namely diamond nitrogen-vacancy (NV) centers. By employing a wide-field magnetic field measurement technique based on NV centers, we rapidly obtain the first-order magnetic field distribution of anomalous regions. Furthermore, we approximate the second-order magnetic field (magnetic gradient tensor) using the differential gradient method. To visualize the electromagnetic anomalous regions boundary, we utilize the tensor invariants of the magnetic gradient tensor components, along with their nonlinear combinations. The identification error rate of the anomalous regions is within 12.5%. Additionally, the electromagnetic field of anomalous regions is simulated showing the measurement accuracy. Our study shows that the experimental results are very similar to the theoretical simulation of the electromagnetic field (error: 7%). This work is essential for advancing electromagnetic field characterization of electronic devices and the advancement of quantum magnetic sensor applications.

5.
Opt Express ; 32(7): 12528-12536, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571073

RESUMO

Diffractive optical element is advantageous for miniaturization, arraying and integration of optical systems. They have been widely used in beam shaping, diffractive imaging, generating beam arrays, spectral optimization and other aspects. Currently, the vast majority of diffractive optics are not tunable. This limits the applicability and functionality of these devices. Here we report a tunable diffractive optical element controlled by light in the visible band. The diffractive optical element consists of a square gold microarray deposited on a deformable substrate. The substrate is made of a liquid crystal elastomer. When pumped by a 532 nm laser, the substrate is deformed to change the crystal lattice. This changes the far-field diffraction pattern of the device. The proposed concept establishes a light-controlled soft platform with great potential for tunable/reconfigurable photonic devices, such as filters, couplers, holograms and structural color displays.

6.
7.
Tissue Eng Regen Med ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568409

RESUMO

BACKGROUND: Hepatic fibrosis (HF) is a common pathological feature of chronic hepatic diseases. We aimed to illuminate the significance of amniotic mesenchymal stem cells (AMSCs)-derived extracellular vesicles (AMSCs-EVs) in HF. METHODS: Human AMSCs-EVs were isolated and identified. HF mice were constructed and treated with EVs. The fibrosis was observed by staining experiments and Western blot (WB) assay. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and hepatic hydroxyproline (Hyp) were detected to confirm liver function. For the in vitro experiments, human hepatic stellate cells were induced with transforming growth factor-ß and treated with EVs. To measure the degree of HF, the expression of alpha-smooth muscle actin (α-SMA) and Collagen I was detected by WB assay, and cell proliferation was detected by cell counting kit 8 assay. The levels of miR-200a, Zinc finger E-box binding homeobox 1 (ZEB1), and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) were detected by WB and real-time quantitative polymerase chain reaction. The binding of ZEB1 to PIK3R3 and miR-200a to ZEB1 was analyzed by chromatin immunoprecipitation and dual luciferase assays to validate their relationships. RESULTS: Human AMSCs and AMSCs-EVs were obtained. Serum ALT, AST, TBIL, and hepatic Hyp were increased, implying the fibrosis degree was aggravated in HF mice, which was decreased again after EV treatment. EVs inhibited HF degree by reducing α-SMA and Collagen I and promoting cell proliferation. AMSCs-EVs delivered miR-200a into hepatocytes, which up-regulated miR-200a expression, inhibited ZEB1 expression, and reduced its enrichment on the PIK3R3 promoter, therefore inhibiting PIK3R3 expression and alleviating HF. Overexpression of ZEB1 or PIK3R3 attenuated the anti-fibrotic effect of AMSCs-EVs. CONCLUSION: Human AMSCs-derived EVs mediated miR-200a delivery and inhibition of intracellular ZEB1/PIK3R3 axis to exert anti-fibrosis effects.

8.
J Appl Genet ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568413

RESUMO

The identification of biomarkers correlated with colorectal cancer (CRC) prognosis holds substantial importance from both clinical and scientific perspectives. Zinc finger protein 26 (ZNF26) has not been previously investigated or documented in solid tumors; thus, further research is necessary to ascertain its prognostic value in CRC. Gene expression profiles and clinicopathological data were acquired from The Cancer Genome Atlas (TCGA) database. Subsequently, expression correlation was assessed utilizing the TCGA CRC cohort. The prognostic value of ZNF26 was evaluated through Kaplan-Meier (KM) and ROC curve analyses. Following this, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to perform enrichment analysis between high- and low-ZNF26 expression groups. The association between immune cells, immune checkpoint genes, and ZNF26 expression levels was examined. Lastly, the research findings were further validated using CRC tissue samples. The results revealed that, in comparison to healthy controls, CRC significantly reduced ZNF26 expression. Elevated ZNF26 expression was associated with poorer overall survival in CRC patients. Additionally, high ZNF26 expression exhibited an inverse relationship with the immunological score and immune checkpoint gene expression in CRC patients. The findings from the TCGA data analysis were corroborated by the PCR results obtained from CRC tissue samples. ZNF26 is markedly upregulated in colorectal cancer tissues, potentially serving as a biomarker for CRC.

9.
Analyst ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597984

RESUMO

Glioblastoma is the most fatal and insidious malignancy, due to the existence of the blood-brain barrier (BBB) and the high invasiveness of tumor cells. Abnormal mitochondrial viscosity has been identified as a key feature of malignancies. Therefore, this study reports on a novel fluorescent probe for mitochondrial viscosity, called ZVGQ, which is based on the twisted intramolecular charge transfer (TICT) effect. The probe uses 3-dicyanomethyl-1,5,5-trimethylcyclohexene as an electron donor moiety and molecular rotor, and triphenylphosphine (TPP) cation as an electron acceptor and mitochondrial targeting group. ZVGQ is highly selective, pH and time stable, and exhibits rapid viscosity responsiveness. In vitro experiments showed that ZVGQ could rapidly recognize to detect the changes in mitochondrial viscosity induced by nystatin and rotenone in U87MG cells and enable long-term imaging for up to 12 h in live U87MG cells. Additionally, in vitro 3D tumor spheres and in vivo orthotopic tumor-bearing models demonstrated that the probe ZVGQ exhibited exceptional tissue penetration depth and the ability to penetrate the BBB. The probe ZVGQ not only successfully visualizes abnormal mitochondrial viscosity changes, but also provides a practical and feasible tool for real-time imaging and clinical diagnosis of glioblastoma.

10.
Clin Immunol ; : 110206, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38599263

RESUMO

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64+ neutrophils, which highly expressed p75 neurotrophin receptor (p75NTR) in peripheral blood of mice and patients with sepsis-induced ALI. p75NTR+CD64+ neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75NTR gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64+ neutrophils. In vitro, p75NTR+CD64+ neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75NTR activity by soluble p75NTR extracellular domain peptide (p75ECD-Fc) boosted CD64+ neutrophil phagocytic activity and reduced inflammatory cytokine production via activation of the NF-κB pathway. The findings strongly indicate that p75NTR+CD64+ neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI.

11.
Cancer Rep (Hoboken) ; 7(4): e1978, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38599581

RESUMO

BACKGROUND AND AIMS: Oncogenesis and tumor development have been related to oxidative stress (OS). The potential diagnostic utility of OS genes in hepatocellular carcinoma (HCC), however, remains uncertain. As a result, this work aimed to create a novel OS related-genes signature that could be used to predict the survival of HCC patients and to screen OS related-genes drugs that might be used for HCC treatment. METHODS: We used The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database to acquire mRNA expression profiles and clinical data for this research and the GeneCards database to obtain OS related-genes. Following that, biological functions from Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on differentially expressed OS-related genes (DEOSGs). Subsequently, the prognostic risk signature was constructed based on DEOSGs from the TCGA data that were screened by using univariate cox analysis, and the Least Absolute Shrinkage and Selection Operator (LASSO) regression, and multivariate cox analysis. At the same time, we developed a prognostic nomogram of HCC patients based on risk signature and clinical-pathological characteristics. The GEO data was used for validation. We used the receiver operating characteristic (ROC) curve, calibration curves, and Kaplan-Meier (KM) survival curves to examine the prediction value of the risk signature and nomogram. Finally, we screened the differentially expressed OS genes related drugs. RESULTS: We were able to recognize 9 OS genes linked to HCC prognosis. In addition, the KM curve revealed a statistically significant difference in overall survival (OS) between the high-risk and low-risk groups. The area under the curve (AUC) shows the independent prognostic value of the risk signature model. Meanwhile, the ROC curves and calibration curves show the strong prognostic power of the nomogram. The top three drugs with negative ratings were ZM-336372, lestaurtinib, and flunisolide, all of which inversely regulate different OS gene expressions. CONCLUSION: Our findings indicate that OS related-genes have a favorable prognostic value for HCC, which sheds new light on the relationship between oxidative stress and HCC, and suggests potential therapeutic strategies for HCC patients.

12.
Heliyon ; 10(7): e28282, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38601554

RESUMO

Objective: Differentially expressed genes (DEGs) in lung adenocarcinoma (LUAD) tumor stem cells were screened, and the biological characteristics of NR5A2 gene were investigated. Methods: The expression and prognosis of NR5A2 in human LUAD were predicted and analyzed through bioinformatics analysis from a human cancer database. Gene expression and clinical data of LUAD tumor and normal lung tissues were obtained from The Cancer Genome Atlas (TCGA) database, and DEGs associated with lung cancer tumor stem cells (CSCs) were screened. Univariate and multivariate Cox regression models were used to screen and establish prognostic risk prediction models. The immune function of the patients was scored according to the model, and the relative immune functions of the high- and low-risk groups were compared to determine the difference in survival prognosis between the two groups. In addition, we calculated the index of stemness based on the transcriptome of the samples using one-class linear regression (OCLR). Results: Bioinformatics analysis of a clinical cancer database showed that NR5A2 was significantly decreased in human LUAD tissues than in normal lung tissues, and the decrease in NR5A2 gene expression shortened the overall survival and progression-free survival of patients with LUAD. Conclusion: The NR5A2 gene may regulate LUAD tumor stem cells through selective splicing mutations, thereby affecting the survival and prognosis of patients with lung cancer, and the NR5A2 gene may regulate CSCs through single nucleotide polymorphism.

14.
Fish Shellfish Immunol ; 148: 109510, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38521143

RESUMO

The signal transducer and activator of transcription 2 (STAT2), a downstream factor of type I interferons (IFNs), is a key component of the cellular antiviral immunity response. However, the role of STAT2 in the upstream of IFN signaling, such as the regulation of pattern recognition receptors (PRRs), remains unknown. In this study, STAT2 homologue of black carp (Mylopharyngodon piceus) has been cloned and characterized. The open reading frame (ORF) of bcSTAT2 comprises 2523 nucleotides and encodes 841 amino acids, which presents the conserved structure to that of mammalian STAT2. The dual-luciferase reporter assay and the plaque assay showed that bcSTAT2 possessed certain IFN-inducing ability and antiviral ability against both spring viremia of carp virus (SVCV) and grass carp reovirus (GCRV). Interestingly, we detected the association between bcSTAT2 and bcRIG-I through co-immunoprecipitation (co-IP) assay. Moreover, when bcSTAT2 was co-expressed with bcRIG-I, bcSTAT2 obviously suppressed bcRIG-I-induced IFN expression and antiviral activity. The subsequent co-IP assay and immunoblotting (IB) assay further demonstrated that bcSTAT2 inhibited K63-linked polyubiquitination but not K48-linked polyubiquitination of bcRIG-I, however, did not affect the oligomerization of bcRIG-I. Thus, our data conclude that black carp STAT2 negatively regulates RIG-I through attenuates its K63-linked ubiquitination, which sheds a new light on the regulation of the antiviral innate immunity cascade in vertebrates.


Assuntos
Carpas , Doenças dos Peixes , Infecções por Reoviridae , Reoviridae , Infecções por Rhabdoviridae , Animais , Carpas/genética , Carpas/metabolismo , Infecções por Rhabdoviridae/veterinária , Fator de Transcrição STAT2/genética , Fator de Transcrição STAT2/metabolismo , Reoviridae/fisiologia , Imunidade Inata/genética , Proteínas de Peixes , Mamíferos/metabolismo
15.
Proc Natl Acad Sci U S A ; 121(14): e2317492121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38547056

RESUMO

Energy metabolism is highly interdependent with adaptive cell migration in vivo. Mechanical confinement is a critical physical cue that induces switchable migration modes of the mesenchymal-to-amoeboid transition (MAT). However, the energy states in distinct migration modes, especially amoeboid-like stable bleb (A2) movement, remain unclear. In this report, we developed multivalent DNA framework-based nanomachines to explore strategical mitochondrial trafficking and differential ATP levels during cell migration in mechanically heterogeneous microenvironments. Through single-particle tracking and metabolomic analysis, we revealed that fast A2-moving cells driven by biomimetic confinement recruited back-end positioning of mitochondria for powering highly polarized cytoskeletal networks, preferentially adopting an energy-saving mode compared with a mesenchymal mode of cell migration. We present a versatile DNA nanotool for cellular energy exploration and highlight that adaptive energy strategies coordinately support switchable migration modes for facilitating efficient metastatic escape, offering a unique perspective for therapeutic interventions in cancer metastasis.


Assuntos
Amoeba , Linhagem Celular Tumoral , Movimento Celular , Fenômenos Físicos
16.
Heliyon ; 10(5): e26847, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38439877

RESUMO

Enteroviruses are major etiological agents of aseptic meningitis globally, however information on circulating enterovirus types associated with this disease in Wuxi, China is limited. In this study, cerebrospinal fluid samples were collected from 20 pediatric aseptic meningitis cases in a Wuxi hospital in 2020 and subjected to metagenomic analysis to detect pathogens. Enterovirus B was detected in 9 cases, including 7 echovirus 18 (E18) and 2 echovirus 11 (E11) strains. The E18 strains exhibited 87.5-98.2% nucleotide identity and phylogenetically clustered with other China E18 strains, while the E11 strains showed 97.59% identity and clustered within the D5 subgroup along with other China E11 strains. One E18 strain was identified as a novel recombinants with a distinct recombination breakpoint within 3D gene. These findings expand knowledge on enteroviruses associated with pediatric aseptic meningitis in Wuxi, and highlight the circulation of genetically diverse E18 and E11 strains, including novel E18 recombinants. Characterization of enterovirus diversity by metagenomic analysis is important for molecular diagnosis and epidemiological tracking of aseptic meningitis cases. Continued surveillance of circulating enterovirus strains in Wuxi that may cause future outbreaks is warranted.

17.
Clin Rheumatol ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38446355

RESUMO

OBJECTIVE: To report a statistical evaluation of symptomatology based on 56 cases of SAPHO syndrome and 352 non-SAPHO involvement cases, to propose a symptomatic scoring system in consideration of early warning for SAPHO syndrome. METHODS: A cohort comprising 56 subjects diagnosed with SAPHO syndrome was reported, as well as 352 non-SAPHO involvement cases, including their chief complaints, skin manifestations, radiological findings, and laboratory tests. We systematically reviewed previous published five representative huge cohorts from different countries to conclude several specific features of SAPHO by comparing with our case series. The score of each specific index is based on respective incidence and comparison of two cohorts was performed. RESULT: In terms of complaint rates, all subjects of two cohorts suffered from osseous pain, which appeared in the anterior chest wall, spine, and limb which were calculated. In respect to dermatological lesions, SAPHO patients suffered from severe acne, and other patients (82.14%) accompanied with palmoplantar pustulosis. Having received radiological examinations, most SAPHO subjects rather than non-SAPHO involvement cases showed abnormal osteoarticular lesions under CT scanning and more detailed information under whole-body bone scintigraphy. Differences also emerged in elevation of inflammation values and rheumatic markers like HLA-B27. Based on our cases and huge cohorts documented, the early warning standard is set to be 5 scores. CONCLUSIONS: SAPHO syndrome case series with 56 subjects were reported and an accumulative scoring system for the early reminder on SAPHO syndrome was proposed. The threshold of this system is set to be 5 points. Key Points • Fifty-six patients diagnosed by SAPHO syndrome with detailed symptoms and radiological findings were reported. • Comparison was made between the 56 SAPHO patients and 352 non-SAPHO involvement cases. • An accumulative scoring system for the early reminder on SAPHO syndrome was proposed and the threshold of this system is set to be five points.

18.
Artigo em Inglês | MEDLINE | ID: mdl-38427138

RESUMO

Adiponectin has previously been investigated for exerting its protective effect against myocardial injury through anti-apoptotic and anti-oxidative actions. Therefore, the present study aimed to investigate the nature and mechanism of adiponectin inhibition of H2O2-induced apoptosis in chicken skeletal myoblasts. Skeletal muscle satellite cells were differentiated and assigned into three groups. Group C was on the blank control group, group H was stimulated with the H2O2 (500 µmol/L, 4 h) alone group, group A + H was pre-treated with adiponectin (10 µg/mL, 24 h) and stimulated with the H2O2 (500 µmol/L, 4 h) group. Cytotoxicity inhibited by adiponectin was evaluated by the CCK-8 assay. The degree of apoptosis and oxidative damage was investigated by the TdT-mediated dUTP nick end labeling (TUNEL) and reactive oxygen species (ROS) staining assays. Oxidative stress was assessed by evaluating lipid peroxidation, superoxide dismutase, and reduced glutathione. Acridine orange (AO) staining detected lysosomal membrane permeability. The changes in mitochondrial membrane potential (MMP) were analyzed using 5,5,6,6'-tetrachloro-1,1,3,3-tetraethylimidacarbocyanine iodide (JC-1) dye under a fluorescence microscope. The lysosomal function, mitochondrial function, and apoptosis-related mRNA and protein expression levels were quantified by real-time quantitative PCR and western blot, respectively. The results suggested that adiponectin treatment attenuated H2O2-induced cytotoxicity and oxidative stress in skeletal myoblasts. Compared with H2O2 treatment, TUNEL and ROS staining demonstrated lower apoptosis upon adiponectin treatment. AO staining confirmed the amelioration of lysosomal membrane damage, and JC-1 staining revealed an increase in mitochondrial membrane potential after adiponectin treatment. At the molecular level, adiponectin treatment inhibited the expression of the lysosomal apoptotic factors cathepsin B, chymotrypsin B, and the mitochondrial apoptotic pathway cytochrome-c (cyt-c) and caspase-8; decreased the apoptotic marker gene Bax; and increased the expression of the anti-apoptotic marker gene Bcl-2. Adiponectin treatment attenuated H2O2-induced apoptosis in skeletal myoblasts, possibly by inhibiting oxidative stress and apoptosis through the lysosomal-mitochondrial axis.

19.
Langmuir ; 40(13): 6786-6805, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38503426

RESUMO

Traditional heterogeneous catalysts are affected in the catalytic hydrogenation of PS by the scale effect, viscosity effect, adhesion effect, and conformational effect, resulting in poor activity and stability. Monolithic Pd-CNTs@FN catalysts could eliminate or weaken the impact of these negative effects. We grew nitrogen-doped carbon nanotubes (NCNTs) on monolithic-foamed nickel (FN) and investigate their growth mechanism. Meanwhile, the feasibility of using the NCNTs@FN carrier for PS hydrogenation reaction was also verified. The growth of NCNTs on FN can be divided into 3 stages: initial growth stage, stable growth stage, and supersaturation stage. Finally, a three-layer structure of NCNT layer, dense carbon layer, and FN skeleton is formed. Two types of structures, nickel-doped carbon nanotubes (NiCNTs) and C-Ni alloy, are formed by combining C and Ni, while four nitrogen-doped structures, NPD, NPR, NG, and NO, are formed by C and N. The prepared carrier exhibited an extremely outstanding specific surface area (2.829 × 106 cm2/g) and strength (no NCNTs falling off after 24 h 500 rpm agitation), as well as high catalytic activity for PS hydrogenation after loaded with Pd (2.13 ± 0.95 nm), with a TOF of up to 27.6 gPS/(gPd•h). After 8 repetitions of the catalyst, there was no significant decrease in activity. This proves the excellent performance of Pd-NCNTs@FN in polymer hydrogenation reactions, laying a solid foundation for further research on the mechanism of NCNTs promoting PS hydrogenation and regulating the growth of NCNTs.

20.
J Cell Mol Med ; 28(7): e18212, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38516826

RESUMO

SBFI26, an inhibitor of FABP5, has been shown to suppress the proliferation and metastasis of tumour cells. However, the underlying mechanism by which SBFI26 induces ferroptosis in breast cancer cells remains largely unknown. Three breast cancer cell lines were treated with SBFI26 and CCK-8 assessed cytotoxicity. Transcriptome was performed on the Illumina platform and verified by qPCR. Western blot evaluated protein levels. Malondialdehyde (MDA), total superoxide dismutase (T-SOD), Fe, glutathione (GSH) and oxidized glutathione (GSSG) were measured. SBFI26 induced cell death time- and dose-dependent, with a more significant inhibitory effect on MDA-MB-231 cells. Fer-1, GSH and Vitamin C attenuated the effects but not erastin. RNA-Seq analysis revealed that SBFI26 treatment significantly enriched differentially expressed genes related to ferroptosis. Furthermore, SBFI26 increased intracellular MDA, iron ion, and GSSG levels while decreasing T-SOD, total glutathione (T-GSH), and GSH levels.SBFI26 dose-dependently up-regulates the expression of HMOX1 and ALOX12 at both gene and protein levels, promoting ferroptosis. Similarly, it significantly increases the expression of SAT1, ALOX5, ALOX15, ALOXE3 and CHAC1 that, promoting ferroptosis while downregulating the NFE2L2 gene and protein that inhibit ferroptosis. SBFI26 leads to cellular accumulation of fatty acids, which triggers excess ferrous ions and subsequent lipid peroxidation for inducing ferroptosis.


Assuntos
Ferroptose , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Dissulfeto de Glutationa , Ferroptose/genética , Peroxidação de Lipídeos , Glutationa , Ferro , Superóxido Dismutase/genética , Espécies Reativas de Oxigênio , Proteínas de Ligação a Ácido Graxo
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