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1.
J Biol Chem ; : 107337, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38705397

RESUMO

APE2 plays important roles in the maintenance of genomic and epigenomic stability including DNA repair and DNA damage response. Accumulating evidence has suggested that APE2 is upregulated in multiple cancers at the protein and mRNA levels, and that APE2 upregulation is correlative with higher and lower overall survival of cancer patients depending on tumor type. However, it remains unknown how APE2 protein abundance is maintained and regulated in cells. Here, we provide the first evidence of APE2 regulation via the post-translational modification (PTM) Ubiquitin. APE2 is poly-ubiquitinated via K48-linked chains and degraded via the Ubiquitin-Proteasome system where K371 is the key residue within APE2 responsible for its ubiquitination and degradation. We further characterize MKRN3 as the E3 ubiquitin ligase for APE2 ubiquitination in cells and in vitro. In summary, this study offers the first definition of the APE2 proteostasis network and lays the foundation for future studies pertaining to the PTM regulation and functions of APE2 in genome integrity and cancer etiology/treatment.

2.
Chem Mater ; 36(9): 4481-4494, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38764752

RESUMO

Four different high-entropy spinel oxide ferrite (HESO) electrode materials containing 5-6 distinct metals were synthesized by a simple, rapid combustion synthesis process and evaluated as conversion anode materials in lithium half-cells. All showed markedly superior electrochemical performance compared to conventional spinel ferrites such as Fe3O4 and MgFe2O4, having capacities that could be maintained above 600 mAh g-1 for 150 cycles, in most cases. X-ray absorption spectroscopy (XAS) results on pristine, discharged, and charged electrodes show that Fe, Co, Ni, and Cu are reduced to the elemental state during the first discharge (lithiation), while Mn is only slightly reduced. Upon recharge (delithiation), Fe is reoxidized to an average oxidation state of about 2.6+, while Co, Ni, and Cu are not reoxidized. The ability of Fe to be oxidized past 2+ accounts for the high capacities observed in these materials, while the presence of metallic elements after the initial lithiation provides an electronically conductive network that aids in charge transfer.

3.
Environ Mol Mutagen ; 65 Suppl 1: 4-8, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38619433

RESUMO

This Special Issue (SI) of Environmental and Molecular Mutagenesis (EMM), entitled "Inspiring Basic and Applied Research in Genome Integrity Mechanisms," is to update the community on recent findings and advances on genome integrity mechanisms with emphasis on their importance for basic and environmental health sciences. This SI includes two research articles, one brief research communication, and four reviews that highlight cutting edge research findings and perspectives, from both established leaders and junior trainees, on DNA repair mechanisms. In particular, the authors provided an updated understanding on several distinct enzymes (e.g., DNA polymerase beta, DNA polymerase theta, DNA glycosylase NEIL2) and the associated molecular mechanisms in base excision repair, nucleotide excision repair, and microhomology-mediated end joining of double-strand breaks. In addition, genome-wide sequencing analysis or site-specific mutational signature analysis of DNA lesions from environmental mutagens (e.g., UV light and aflatoxin) provide further characterization and sequence context impact of DNA damage and mutations. This SI is dedicated to the legacy of Dr. Samuel H. Wilson from the U.S. National Institute of Environmental Health Sciences at the National Institutes of Health.


Assuntos
Aniversários e Eventos Especiais , Reparo do DNA , Reparo do DNA/genética , Dano ao DNA/genética , DNA/genética , Mutação , Reparo do DNA por Junção de Extremidades
4.
ACS Nano ; 18(15): 10454-10463, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38572806

RESUMO

DNA isothermal amplification techniques have been applied extensively for evaluating nucleic acid inputs but cannot be implemented directly on other types of biomolecules. In this work, we designed a proximity activation mechanism that converts protein input into DNA barcodes for the DNA exponential amplification reaction, which we termed PEAR. Several design parameters were identified and experimentally verified, which included the choice of enzymes, sequences of proximity probes and template strand via the NUPACK design tool, and the implementation of a hairpin lock on the proximity probe structure. Our PEAR system was surprisingly more robust against nonspecific DNA amplification, which is a major challenge faced in existing formats of the DNA-based exponential amplification reaction. The as-designed PEAR exhibited good target responsiveness for three protein models with a dynamic range of 4-5 orders of magnitude down to femtomolar input concentration. Overall, our proposed protein-to-DNA converter module led to the development of a stable and robust configuration of the DNA exponential amplification reaction to achieve high signal gain. We foresee this enabling the use of protein inputs for more complex molecular evaluation as well as ultrasensitive protein detection.


Assuntos
Técnicas Biossensoriais , DNA , DNA/genética , DNA/química , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas Biossensoriais/métodos
5.
J Gastrointest Oncol ; 15(1): 179-189, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38482244

RESUMO

Background: Adjuvant chemotherapy is considered for stage II colorectal cancer (CRC) patients with poor prognostic risk factors. However, current stratification algorithms are still insufficient to identify high-risk patients. Methods: We conducted a screening strategy to define ZNF326 based on quantitative proteomics in 11 paired CRC patients selected by a nested case-control design, and tested the association between ZNF326 expression level with the prognosis of stage II CRC patients and the benefit from adjuvant chemotherapy in public datasets; further investigation was conducted through subgroup analyses. Results: We found that low ZNF326 expression was significantly associated with a lower 5-year overall survival (OS) rate among stage II patients in both the discovery [P=0.008; hazard ratio (HR): 3.13, 95% confidence interval (CI): 1.29-7.58] and validation (P=0.025; HR: 1.98, 95% CI: 1.08-3.65) cohorts. In the Cox multivariable analysis, low ZNF326 expression was both associated with shorter OS after adjustment for age, sex, and adjuvant chemotherapy in the discovery and validation data sets. Subgroup analyses yielded largely similar results. In a pooled database, the rate of 5-year OS was higher among stage II ZNF326-high tumors who were treated with adjuvant chemotherapy than it was among those who were not treated with adjuvant chemotherapy (P=0.011; HR: 0.28, 95% CI: 0.10-0.80). Conclusions: ZNF326 has the potential to be used in clinical practice for risk classification. ZNF326-low expression level identified a subgroup of patients with high-risk stage II CRC who appeared to less benefit from adjuvant chemotherapy.

6.
Water Res ; 255: 121503, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38537488

RESUMO

With the increasing adoption of carbon-based strategies to enhance methanogenic processes, there is a growing concern regarding the correlation between biochar properties and its stimulating effects on anaerobic digestion (AD) under ammonia inhibition. This study delves into the relevant characteristics and potential mechanisms of biochar in the context of AD system under ammonia inhibition. The introduction of optimized biochar, distinguished by rich CO bond, abundant defect density, and high electronic capacity, resulted in a significant reduction in the lag period of anaerobic digestion system under 5.0 g/L ammonia stress, approximately by around 63 % compared to the control one. Biochar helps regulate the community structure, promotes the accumulation of acetate-consuming bacteria, in the AD system under ammonia inhibition. More examinations show that biochar promotes direct interspecies electron transfer in AD system under ammonia inhibition, as evidenced by diminished levels of bound electroactive extracellular polymeric substances, increased abundance of electroactive bacteria, and notably, the up-regulation of direct interspecies electron transfer associated genes, including the conductive pili and Cytochrome C genes, as revealed by meta-transcriptomic analysis. Additionally, gene expression related to proteins associated with ammonium detoxification were found to be up-regulated in systems supplemented with biochar. These findings provide essential evidence and insights for the selection and potential engineering of effective biochar to enhance AD performance under ammonia inhibition.

7.
Cell Rep ; 43(3): 113878, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38431844

RESUMO

Cytidine deaminase defines the properties of cytosine base editors (CBEs) for C-to-T conversion. Replacing the cytidine deaminase rat APOBEC1 (rA1) in CBEs with a human APOBEC3A (hA3A) improves CBE properties. However, the potential CBE application of macaque A3A orthologs remains undetermined. Our current study develops and evaluates engineered CBEs based on Macaca fascicularis A3A (mA3A). Here, we demonstrate that BE4-mA3A and its RNA-editing-derived variants exhibit improved CBE properties, except for DNA off-target activity, compared to BE3-rA1 and BE4-rA1. Unexpectedly, deleting Ser-Val-Arg (SVR) in BE4-mA3A dramatically reduces DNA and RNA off-target activities and improves editing accuracy, with on-target efficiency unaffected. In contrast, a chimeric BE4-hA3A-SVR+ shows editing efficiency increased by about 50%, with other properties unaffected. Our findings demonstrate that mA3A-based CBEs could provide prototype options with advantages over rA1- and hA3A-based CBEs for further optimization, highlighting the importance of the SVR motif in defining CBE intrinsic properties.


Assuntos
Citosina , Edição de Genes , Proteínas , Ratos , Animais , Humanos , Macaca fascicularis , Citidina Desaminase/genética , RNA/genética , DNA/genética , Sistemas CRISPR-Cas
8.
J Hazard Mater ; 469: 134096, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38522195

RESUMO

Arsenic (As)-contaminated soil poses great health risk to human mostly through inadvertent oral exposure. We investigated CaAl-layered double hydroxide (CaAl-LDH), a promising immobilising agent, for the remediation of As-contaminated Chinese soils. The effects on specific soil properties and As fractionation were analyzed, and changes in the health risk of soil As were accurately assessed by means of advanced in vivo mice model and in vitro PBET-SHIME model. Results showed that the application of CaAl-LDH significantly increased soil pH and concentration of Fe and Al oxides, and effectively converted active As fractions into the most stable residual fraction, guaranteeing long-term remediation stability. Based on in vivo test, As relative bioavailability was significantly reduced by 37.75%. Based on in vitro test, As bioaccessibility in small intestinal and colon phases was significantly reduced by 25.65% and 28.57%, respectively. Furthermore, As metabolism (reduction and methylation) by the gut microbiota inhabiting colon was clearly observed. After immobilisation with CaAl-LDH, the concentration of bioaccessible As(Ⅴ) in the colon fluid was significantly reduced by 61.91%, and organic As (least toxic MMA(V) and DMA(V)) became the main species, which further reduced the health risk of soil As. In summary, CaAl-LDH proved to be a feasible option for immobilisation remediation of As-contaminated soils, and considerable progress was made in relevant health risk assessment.


Assuntos
Arsênio , Poluentes do Solo , Animais , Humanos , Camundongos , Arsênio/química , Disponibilidade Biológica , Poluentes do Solo/análise , Solo/química , Medição de Risco
9.
BMC Med Genomics ; 17(1): 46, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38303044

RESUMO

OBJECTIVE: To analyze the clinical phenotype and genetic characteristics of a female proband carrying a novel mutation in the DMD gene with non-random X-chromosome inactivation in a large pedigree with pseudohypertrophic muscular dystrophy. METHODS: Clinical information of the female proband, her monozygotic twin sister, and other family members were collected. Potential pathogenic variants were detected with Multiplex Ligation-dependent Probe Amplification (MLPA) and whole-exome sequencing (WES). Methylation-sensitive restriction enzyme (HhaI) was employed for X-chromosome inactivation analysis. RESULTS: The proband was a female over 5 years old, displayed clinical manifestations such as elevated creatine kinase (CK) levels and mild calf muscle hypertrophy. Her monozygotic twin sister exhibited normal CK levels and motor ability. Her uncle and cousin had a history of DMD. WES revealed that the proband carried a novel variant in the DMD (OMIM: 300,377) gene: NM_004006.3: c.3051_3053dup; NP_003997.2: p.Tyr1018*. In this pedigree, five out of six female members were carriers of this variant, while the cousin and uncle were hemizygous for this variant. X-chromosome inactivation analysis suggested non-random inactivation in the proband. CONCLUSION: The c.3051_3053dup (p.Tyr1018*) variant in the DMD gene is considered to be the pathogenic variant significantly associated with the clinical phenotype of the proband, her cousin, and her uncle within this family. Integrating genetic testing with clinical phenotype assessment can be a valuable tool for physicians in the diagnosis of progressive muscular dystrophies, such as Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD).


Assuntos
Distrofia Muscular de Duchenne , Humanos , Feminino , Pré-Escolar , Distrofia Muscular de Duchenne/genética , Testes Genéticos , Fenótipo , Mutação , Cromossomos
10.
ACS Appl Mater Interfaces ; 16(8): 10398-10406, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38380978

RESUMO

The rapid evolution of the Internet of Things has engendered increased requirements for low-cost, self-powered UV photodetectors. Herein, high-performance self-driven UV photodetectors are fabricated by designing asymmetric metal-semiconductor-metal structures on the high-quality large-area CsCu2I3 microwire arrays. The asymmetrical depletion region doubles the photocurrent and response speed compared to the symmetric structure device, leading to a high responsivity of 233 mA/W to 355 nm radiation. Notably, at 0 V bias, the asymmetric device produces an open-circuit voltage of 356 mV and drives to a short-circuit current of 372 pA; meanwhile, the switch ratio (Iph/Idark) reaches up to 103, indicating its excellent potential for detecting weak light. Furthermore, the device maintains stable responses throughout 10000 UV-light switch cycles, with negligible degradation even after 90-day storage in air. Our work establishes that CsCu2I3 is a good candidate for self-powered UV detection and thoroughly demonstrates its potential as a passive device.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38267387

RESUMO

Sarcopenic obesity (SO) is an age-related disease characterized by the coexistence of excessive adiposity and low muscle mass or function. Although obesity and sarcopenia are heritable conditions, the genetic determinants of SO have not been fully understood. We conducted a large-scale exome-wide association analysis of SO in a sequenced sample of 2 887 cases and 113 284 controls and an imputed sample of 4 003 cases and 161 990 controls in the UK Biobank cohort. Single-variant association analysis identified one locus 1q41 (lead SNP rs1417066, LYPLAL1-AS1, odds ratio [OR] = 1.15, 95% confidence interval [CI] = [1.11-1.19], p = 1.75 × 10-14) that was significantly associated with SO at the exome-wide significance level (p < 1 × 10-8). Colocalization analysis in the Genotype-Tissue Expression expression quantitative trait locus database showed that LYPLAL1-AS1 was colocalized with SO in multiple musculoskeletal-related tissues. Gene-based burden test of rare loss-of-function variants identified 5 genes at the gene-wise significance level (p < 4.3 × 10-6): PDE3B (OR = 2.48, p = 1.10 × 10-6), MYOZ3 (OR = 25.49, p = 1.41 × 10-7), SLC15A3 (OR = 4.75, p = 6.82 × 10-7), RNF130 (OR = 25.83, p = 4.07 × 10-6), and TNK2 (OR = 4.25, p = 8.75 × 10-8). Overall, our study uncovered the genetic effects of both common and rare variants on SO susceptibility, expanded existing knowledge of the genetic architecture of SO, and improved understanding of the genetic mechanisms underlying SO.


Assuntos
Sarcopenia , Humanos , Sarcopenia/genética , Predisposição Genética para Doença , Exoma/genética , Estudo de Associação Genômica Ampla , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Proteínas Tirosina Quinases/genética
12.
Invest Ophthalmol Vis Sci ; 65(1): 13, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38175639

RESUMO

Purpose: The purpose of this study was to identify key genes and their regulatory networks that are conserved in mouse models of age-related macular degeneration (AMD) and human AMD. Methods: Retinal RNA-Seq was performed in laser-induced choroidal neovascularization (CNV) mice at day 3 and day 7 after photocoagulation. Mass spectrometry-based proteomic analysis was performed with retinas collected at day 3. Retinal RNA-Seq data was further compared among mouse models of laser-induced CNV and NaIO3-induced retinal degeneration (RD) and a large AMD cohort. Results: Retinal RNA-Seq revealed upregulated genes and pathways related to innate immunity and inflammation in mice with CNV, with more profound changes at the early stage (day 3). Proteomic analysis further validated these differentially expressed genes and their networks in retinal inflammation during CNV. Notably, the most evident overlap in the retina of mice with laser-induced CNV and NaIO3-induced RD was the upregulation of inflammation-related genes, pointing to a common vital role of retinal inflammation in the early stage for both mouse AMD models. Further comparative transcriptomic analysis of the mouse AMD models and human AMD identified 48 conserved genes mainly involved in inflammation response. Among them, B2M, C3, and SERPING1 were upregulated in all stages of human AMD and the mouse AMD models compared to controls. Conclusions: Our study demonstrates conserved molecular changes related to retinal inflammation in mouse AMD models and human AMD and provides new insight into the translational application of these mouse models in studying AMD mechanisms and treatments.


Assuntos
Neovascularização de Coroide , Degeneração Macular , Degeneração Retiniana , Humanos , Animais , Camundongos , Proteômica , Degeneração Macular/genética , Retina , Inflamação , Neovascularização de Coroide/genética , Modelos Animais de Doenças
13.
Heliyon ; 10(1): e24095, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38226211

RESUMO

Purpose: This study aims to investigate the influence of the build angle on the surface characteristics, accuracy, and dimensional stability of digital light processing (DLP) printed resin bases. Material and methods: Rectangular and complete denture base samples were fabricated at 0, 45, and 90-degree angles (n = 5 for rectangular samples; n = 10 for maxillary and mandibular denture base samples) using a DLP printer. Surface morphology and roughness were assessed using a profilometer, followed by measuring hydrophilicity with a contact angle meter. Accuracy (trueness and precision) and dimensional stability were evaluated at intervals of 1, 3, 7, 14, 28, and 42 days after base printing using best-fit-alignment and deviation analysis in 3D software. Statistical analysis was performed using one-way ANOVA for surface characteristics (α = 0.05), multi-way ANOVA for accuracy and dimensional stability data, and Tukey's test for post-hoc comparisons. Results: The 0-degree group exhibited significantly lower mean roughness (1.27 ± 0.19 µm) and contact angle (80.50 ± 3.71°) (P < 0.001) compared to the 90-degree and 45-degree groups. The 0-degree build angle led to superior trueness (maxilla: 77.80 ± 9.35 µm, mandible: 61.67 ± 10.32 µm) and precision (maxilla: 27.51 ± 7.43 µm, mandible: 53.50 ± 15.16 µm) compared to other groups (P < 0.001). Maxillary base precision was superior to mandibular base precision (P < 0.001). The maxillary base exhibited less dimensional deviation than the mandibular base. The 90-degree group showed the highest deviation compared to the other two groups, and all groups' deviations increased over time (P < 0.001). Conclusions: The build angle significantly influences the surface characteristics, accuracy, and dimensional stability of DLP-printed denture bases. A 0-degree build angle provides the most favorable performance. The maxillary base displayed superior precision and dimensional stability than the mandibular base.

14.
Anticancer Drugs ; 35(2): 129-139, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37615540

RESUMO

Colorectal cancer (CRC) is one of the world's most common and deadly cancers. According to GLOBOCAN2020's global incidence rate and mortality estimates, CRC is the third main cause of cancer and the second leading cause of cancer-related deaths worldwide. The US Food and Drug Administration has approved auranofin for the treatment of rheumatoid arthritis. It is a gold-containing chemical that inhibits thioredoxin reductase. Auranofin has a number of biological activities, including anticancer activity, although it has not been researched extensively in CRC, and the mechanism of action on CRC cells is still unknown. The goal of this research was to see how Auranofin affected CRC cells in vivo and in vitro . The two chemical libraries were tested for drugs that make CRC cells more responsive. The CCK-8 technique was used to determine the cell survival rate. The invasion, migration, and proliferation of cells were assessed using a transwell test and a colony cloning experiment. An electron microscope was used to observe autophagosome formation. Western blotting was also used to determine the degree of expression of related proteins in cells. Auranofin's tumor-suppressing properties were further tested in a xenograft tumor model of human SW620 CRC cells. Auranofin dramatically reduced the occurrence of CRC by decreasing the proliferation, migration, and invasion of CRC cells, according to our findings. Through a mTOR-dependent mechanism, auranofin inhibits the epithelial-mesenchymal transition (EMT) and induces autophagy in CRC cells. Finally, in-vivo tests revealed that auranofin suppressed tumor growth in xenograft mice while causing no harm. In summary, auranofin suppresses CRC cell growth, invasion, and migration. Auranofin inhibits the occurrence and progression of CRC by decreasing EMT and inducing autophagy in CRC cells via a mTOR-dependent mechanism. These findings suggest that auranofin could be a potential chemotherapeutic medication for the treatment of human CRC.


Assuntos
Auranofina , Neoplasias Colorretais , Humanos , Animais , Camundongos , Auranofina/farmacologia , Auranofina/uso terapêutico , Linhagem Celular Tumoral , Serina-Treonina Quinases TOR/metabolismo , Neoplasias Colorretais/patologia , Autofagia , Transição Epitelial-Mesenquimal , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica
16.
Environ Res ; 242: 117775, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38029815

RESUMO

The development of cost-efficient biochar adsorbent with a simple preparation method is essential to constructing efficient wastewater treatment system. Here, a low-cost waste carton biochar (WCB) prepared by a simple two-step carbonization was applied in efficiently removing Rhodamine B (RhB) in aqueous environment. The maximum ability of WCB for RhB adsorption was 222 mg/g, 6 and 10 times higher than both of rice straw biochar (RSB) and broadbean shell biochar (BSB), respectively. It was mainly ascribed to the mesopore structure (3.0-20.4 nm) of WCB possessing more spatial sites compared to RSB (2.2 nm) and BSB (2.4 nm) for RhB (1.4 nm✕1.1 nm✕0.6 nm) adsorption. Furthermore, external mass transfer (EMT) controlled mass transfer resistance (MTR) of the RhB sorption process by WCB which was fitted with the Langmuir model well. Meanwhile, the adsorption process was dominated by physisorption through van der Waals forces and π-π interactions. A mixture of three dyes in river water was well removed by using WCB. This work provides a straightforward method of preparing mesoporous biochar derived from waste carton with high-adsorption capacity for dye wastewater treatment.


Assuntos
Carvão Vegetal , Águas Residuárias , Poluentes Químicos da Água , Corantes/química , Eliminação de Resíduos Líquidos/métodos , Adsorção , Poluentes Químicos da Água/análise , Cinética
17.
Inflammation ; 47(2): 822-836, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38148453

RESUMO

Genomic instability is a key driving force for the development and progression of many age-related neurodegenerative diseases and central nervous system (CNS) cancers. Recently, the cytosolic DNA sensor, cyclic GMP-AMP synthase (cGAS), has been shown to detect and respond to self-DNA accumulation resulting from DNA damaging insults in peripheral cell types. cGAS has been shown to be important in the responses of microglia to DNA viruses and amyloid beta, and we have reported that it underlies the responses of human microglia to exogenous DNA. However, the role of this cytosolic sensor in the detection of self-DNA by glia is poorly understood and its ability to mediate the cellular responses of human microglia to genotoxic DNA damage has not been established. Here, we describe the ability of ionizing radiation and oxidative stress to elicit genomic DNA damage in human microglial cells and to stimulate the production of key inflammatory mediators by these cells in an NF-kB dependent manner. Importantly, we have utilized CRISPR/Cas9 and siRNA-mediated knockdown approaches and a pharmacological inhibitor of the cGAS adaptor protein stimulator of interferon genes (STING) to demonstrate that the cGAS-STING pathway plays a critical role in the generation of these microglial immune responses to such genotoxic insults. Together, these studies support the notion that cGAS mediates the detection of cytosolic self-DNA by microglia, providing a potential mechanism linking genomic instability to the development of CNS cancers and neurodegenerative disorders.


Assuntos
Dano ao DNA , Proteínas de Membrana , Microglia , Nucleotidiltransferases , Humanos , Nucleotidiltransferases/metabolismo , Microglia/metabolismo , Proteínas de Membrana/metabolismo , Estresse Oxidativo , Inflamação/metabolismo , NF-kappa B/metabolismo
18.
Front Pharmacol ; 14: 1250216, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38053836

RESUMO

Background: The temporomandibular joint is often afflicted by osteoarthritis (TMJOA), causing pain and dysfunction, which is particularly prevalent in the elderly population. IL-37 is effective in avoiding excessive inflammatory damage to the organism. This article investigates the role and mechanism of intracellular IL-37 in TMJOA. Methods: Enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, Western blotting, Senescence-associated ß-galactosidase staining, immunofluorescence, and lentivirus were performed to elucidate the underlying mechanism. Results: The results confirmed that IL-37 in synovial cells decreased with aging. Inflammatory stimulus elevated intracellular IL-37 in synoviocytes, while lentiviral knockdown of IL-37 resulted in more inflammatory factor production. Dynamic changes of IL-37 were observed in the nucleus and supernatant. In addition, Caspease-1 inhibitor hindered intracellular IL-37 maturation, and Smad3 inhibitor caused the loss of nuclear translocation of mature IL-37. Transfection of synovial cells with IL-37-expressing lentivirus resulted in relief not only of synovitis but also of the cartilage damage and inflammation caused by synovitis. Conclusion: This study provides new insights into the intracellular anti-inflammatory mechanism of IL-37. It also confirms that IL-37 decreases with cellular senescence and that increasing intracellular IL-37 can effectively treat synovitis and synovitis-induced inflammatory damage to cartilage.

19.
Cancer Imaging ; 23(1): 116, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38041154

RESUMO

BACKGROUND: The correlation between the preoperative splenic area measured on CT scans and the overall survival (OS) of early-stage non-small cell lung cancer (NSCLC) patients remains unclear. METHODS: A retrospective discovery cohort and validation cohort consisting of consecutive NSCLC patients who underwent resection and preoperative CT scans were created. The patients were divided into two groups based on the measurement of their preoperative splenic area: normal and abnormal. The Cox proportional hazard model was used to analyse the correlation between splenic area and OS. RESULTS: The discovery and validation cohorts included 2532 patients (1374 (54.27%) males; median (IQR) age 59 (52-66) years) and 608 patients (403 (66.28%) males; age 69 (62-76) years), respectively. Patients with a normal splenic area had a 6% higher 5-year OS (n = 727 (80%)) than patients with an abnormal splenic area (n = 1805 (74%)) (p = 0.007) in the discovery cohort. A similar result was obtained in the validation cohort. In the univariable analysis, the OS hazard ratios (HRs) for the patients with abnormal splenic areas were 1.32 (95% confidence interval (CI): 1.08, 1.61) in the discovery cohort and 1.59 (95% CI: 1.01, 2.50) in the validation cohort. Multivariable analysis demonstrated that abnormal splenic area was independent of shorter OS in the discovery (HR: 1.32, 95% CI: 1.08, 1.63) and validation cohorts (HR: 1.84, 95% CI: 1.12, 3.02). CONCLUSION: Preoperative CT measurements of the splenic area serve as a prognostic indicator for early-stage NSCLC patients, offering a novel metric with potential implications for personalized therapeutic strategies in top-tier oncology research.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Prognóstico , Estudos Retrospectivos , Estadiamento de Neoplasias , Biomarcadores
20.
Huan Jing Ke Xue ; 44(12): 6564-6575, 2023 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-38098384

RESUMO

Based on the online monitoring data of volatile organic compounds(VOCs) and ozone(O3) in Liaocheng in June 2021, the concentration levels, compositional characteristics, daily variation characteristics, and ozone formation potential(OFP) of VOCs on polluted days and clean days were systematically analyzed. Potential source areas of VOCs were identified by the potential source contribution function(PSCF) and concentration-weighted trajectory(CWT). The sources of VOCs in Liaocheng were analyzed using the characteristic species ratio and positive matrix factorization(PMF). The results showed that the hourly mean values of VOCs concentrations on polluted days and clean days in Liaocheng in June 2021 were(115.38±59.12) µg·m-3 and(88.10±33.04) µg·m-3, respectively, and the concentration levels of VOCs in each category showed that oxygenated volatile organic compounds(OVOCs)>alkanes>halogenated hydrocarbons>aromatic hydrocarbons>alkenes>alkynes>organosulfur. VOCs species with large differences in concentrations between polluted and clean days were among the top ten species of the hourly mean VOCs concentrations. The daily trends of concentrations of total VOCs, alkanes, alkynes, aromatic hydrocarbons, halogenated hydrocarbons, and organosulfur showed that the daytime concentrations were lower than the nighttime concentrations, and the daily changes in OVOCs concentrations showed the characteristics of high in the daytime and low at nighttime. The OFP was 285.29 µg·m-3 on polluted days and 212.00 µg·m-3 on clean days, and OVOCs, alkenes, and aromatic hydrocarbons contributed significantly to ozone formation. The PSCF and CWT results found that the potential source areas of VOCs in Liaocheng were concentrated in the northern and northeastern part of Dongchangfu District and the central and southwestern part of Chiping District. The results of the characteristic species ratio indicated that the VOCs in Liaocheng might have been more from coal combustion, gasoline volatilization, and motor vehicle exhaust. The results of PMF showed that industrial emission sources(30.57%), motor vehicle exhaust and oil and gas volatilization sources(19.44%), combustion sources(17.23%), air aging and secondary generation sources(13.69%), solvent usage sources(12.75%), and natural sources(6.32%) were the main sources of VOCs in Liaocheng.

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