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2.
Bioresour Technol ; 410: 131257, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39128639

RESUMEN

Fungi capable of simultaneous nitrogen and phosphorus removal from wastewater is rarely found. Here, a novel fungal strain (SNDM1) performing heterotrophic nitrification, aerobic denitrification, and phosphate removal was isolated and identified as Mucor circinelloides. The favorable nutrient removal conditions by the strain using glucose were C/N ratios of 25-30, salinities of 0 %-3 %, and pH of 7.5. Strain SNDM1 achieved ammonium, nitrite, nitrate, and phosphate removal rates of 5.23, 10.08, 4.88, and 0.97 mg/L/h. Nitrogen balance indicated that gaseous (18.60 %-24.55 %) and intracellular nitrogen (43.76 %-70.63 %) were primary fate of initial nitrogen. Enzyme activity revealed that ammonium removal occurred through heterotrophic nitrification and aerobic denitrification. Removed phosphorus was mainly transformed into cell membranes (56 %-64 %) and extracellular polymeric substances (20 %-26 %). Orthophosphate was the major intracellular phosphorus species, while polyphosphate and pyrophosphate existed extracellularly. These findings highlight the potential of this fungal strain for bioremediating polluted wastewater.

3.
Oncology ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134010

RESUMEN

INTRODUCTION: Laryngeal squamous cell carcinoma (LSCC) is the most common type of laryngeal cancer, with around 60% of patients being diagnosed at an advanced stage. Recently, cancer-derived sialylated immunoglobulin G (SIA-IgG) has been suggested to play a role in the progression of various epithelial tumors, but its significance in LSCC remains unknown. This study aims to investigate the clinical significance of SIA-IgG as a novel biomarker in relation to the initiation, progression, and prognostication of LSCC. METHODS: Immunohistochemistry (IHC) were utilized to assess SIA-IgG expression in tumor samples from 75 LSCC patients, aiming to investigate its correlation with clinical prognosis. Vitro functional experiments were conducted to explore the impact of SIA-IgG expression on the proliferative and migratory abilities of laryngocarcinoma cells. RESULTS: High expression of SIA-IgG was associated with pT stage, pN stage, TNM stage, and recurrence during follow-up, and was correlated with poor disease-free survival (DFS) and overall survival (OS). Multivariate Cox analysis demonstrated that SIA-IgG served as an independent risk factor for OS and DFS. Knocking down SIA-IgG significantly weakened laryngocarcinoma cells' proliferation, clonogenesis, and migration abilities. CONCLUSIONS: The frequent expression of SIA-IgG in LSCC is significantly associated with poor prognosis. High levels of SIA-IgG can enhance proliferation and migration in laryngocarcinoma cells. These findings suggest that SIA-IgG has potential as a novel biomarker for LSCC.

4.
Environ Sci Ecotechnol ; 22: 100454, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39139782

RESUMEN

Carbon mitigation technologies lead to air quality improvement and health co-benefits, while the practical effects of the technologies are dependent on the energy composition, technological advancements, and economic development. In China, mitigation technologies such as end-of-pipe treatment, renewable energy adoption, carbon capture and storage (CCS), and sector electrification demonstrate significant promise in meeting carbon reduction targets. However, the optimization of these technologies for maximum co-benefits remains unclear. Here, we employ an integrated assessment model (AIM/enduse, CAM-chem, IMED|HEL) to analyze air quality shifts and their corresponding health and economic impacts at the provincial level in China within the two-degree target. Our findings reveal that a combination of end-of-pipe technology, renewable energy utilization, and electrification yields the most promising results in air quality improvement, with a reduction of fine particulate matter (PM2.5) by -34.6 µg m-3 and ozone by -18.3 ppb in 2050 compared to the reference scenario. In contrast, CCS technology demonstrates comparatively modest improvements in air quality (-9.4 µg m-3 for PM2.5 and -2.4 ppb for ozone) and cumulative premature deaths reduction (-3.4 million from 2010 to 2050) compared to the end-of-pipe scenario. Notably, densely populated regions such as Henan, Hebei, Shandong, and Sichuan experience the most health and economic benefits. This study aims to project effective future mitigation technologies and climate policies on air quality improvement and carbon mitigation. Furthermore, it seeks to delineate detailed provincial-level air pollution control strategies, offering valuable guidance for policymakers and stakeholders in pursuing sustainable and health-conscious environmental management.

5.
Sci Data ; 11(1): 885, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39143139

RESUMEN

Red swamp crayfish, Procambarus clarkii, is the most cultured freshwater crayfish species. It attracts significant research attention due to its considerable economic importance. However, the limited availability of genome information has impeded further genetic studies and breeding programs. By utilizing Illumina, PacBio, and Hi-C sequencing technologies, we present a more comprehensive and continuous chromosome-level assembly for P. clarkii than the published one. The final genome size is 4.03 Gb, consisting of 2,358 scaffolds with a N50 of 42.87 Mb. Notably, 3.68 Gb, corresponding to 91.42% of the genome, was anchored to 94 chromosomes. The assembly comprises 70.64% repetitive sequences, including 5.21% tandem repeats and 65.40% transposable elements. Additionally, a total of 4,456 non-coding RNAs and 28,852 protein-coding genes were predicted in the P. clarkii genome, with 96.26% of the genes were annotated. This high-quality genome assembly not only represents a significant improvement for the genome of P. clarkii and provides insights into the unique genome evolution, but also offers valuable information for developing freshwater aquaculture and accelerating genetic breeding.


Asunto(s)
Astacoidea , Cromosomas , Genoma , Animales , Astacoidea/genética , Elementos Transponibles de ADN
6.
Int J Mol Sci ; 25(15)2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39125935

RESUMEN

Reversible regulation of N6-methyladenosine (m6A) methylation of eukaryotic RNA via methyltransferases is an important epigenetic event affecting RNA metabolism. As such, m6A methylation plays crucial roles in regulating animal growth, development, reproduction, and disease progression. Herein, we review the latest research advancements in m6A methylation modifications and discuss regulatory aspects in the context of growth, development, and reproductive traits of livestock. New insights are highlighted and perspectives for the study of m6A methylation modifications in shaping economically important traits are discussed.


Asunto(s)
Adenosina , Ganado , Animales , Ganado/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Epigénesis Genética , Metilación , Metiltransferasas/metabolismo , Metiltransferasas/genética
7.
Front Med (Lausanne) ; 11: 1410607, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39170036

RESUMEN

Background: Glaucoma, a leading cause of global blindness, is characterized by optic nerve damage and visual field loss. Previous studies have suggested a potential association between glaucoma and anxiety disorders. However, the causal relationship between these two conditions remains unclear. Methods: In this study, we conducted a Mendelian Randomization analysis to investigate the causal relationship between glaucoma and anxiety disorders. We sourced Genome-Wide Association Study (GWAS) datasets for glaucoma and anxiety with the largest sample sizes from the Integrative Epidemiology Unit OpenGWAS (IEU OpenGWAS) project website. Instrumental variables were selected based on specific criteria, and statistical analyses were performed using the R programming language. Results: After filtering and merging the datasets, a total of 60 Single Nucleotide Polymorphisms (SNPs) were obtained for analysis. Regression models were applied to assess the causal relationship between glaucoma and anxiety disorders. The results from all four methods indicated that glaucoma does not cause anxiety disorders (p > 0.05). Conclusion: Through rigorous Mendelian Randomization analysis, our findings indicate that glaucoma is not a causative factor for anxiety, with minimal influence from confounding factors in this study. These findings enhance our understanding of the relationship between glaucoma and anxiety.

8.
Huan Jing Ke Xue ; 45(8): 4419-4431, 2024 Aug 08.
Artículo en Chino | MEDLINE | ID: mdl-39168662

RESUMEN

Based on the observation data of O3 concentration in Yinchuan in 2022, the monthly variation characteristics of O3 concentrations were analyzed. Further, based on the observation data of meteorological elements, conventional pollutants, and volatile organic compounds (VOCs) concentrations at an urban site in Yinchuan from May to July, the difference in meteorological elements and precursor concentrations between the polluted days and the non-polluted days were compared. Then, the O3 sensitivity and the VOCs sources were discussed using the Framework for 0-D Atmospheric Modeling (F0AM) and positive matrix factorization (PMF) model, respectively. The results showed that: ① The O3 pollution occurred from May to July in 2022, and the concentrations of O3-8h-90per were 156 µg·m-3, 170 µg·m-3, and 174 µg·m-3, respectively, with exceeding standard rates of 9.7%, 26.7%, and 29.0%, respectively. ② Compared with those on the non-polluted days, the hourly mean values of temperature, total solar radiation, and concentrations of various precursors on the O3-polluted days increased, including the volume concentrations of propane, isobutane, ethane, n-butane, and dichloromethane, which increased significantly by 33.1%, 29.1%, 25.0%, 22.7%, and 21.3%, respectively. The results showed that the combined increase in pollutant emissions and adverse meteorological conditions contributed to the formation of O3. ③ From May to July 2022, the top five VOCs species in terms of ozone formation potential (OFP) value on whole, non-polluted, and polluted days were the same. They were acetaldehyde, m/p-xylene, ethylene, isoprene, and toluene, mainly from solvent use sources, natural sources, and chemical industry emissions. ④ The local O3 production was mostly controlled by VOCs, and the relative incremental reactivity (RIR) results revealed that O3 production showed strong positive sensitivity to alkene and aromatic hydrocarbon but showed negative sensitivity to NOx on both polluted and non-polluted days. The relative contributions of active species such as acetone, ethylene, and isobutane to O3 production were high, and the implementation of an emission reduction scheme with the ratio of VOCs to NOx emission reduction much greater than 1 could effectively reduce the local O3 concentration. ⑤ The main sources of atmospheric VOCs in Yinchuan were motor vehicle emission sources (32.3%), process sources (20.7%), combustion sources (19.2%), solvent use sources (12.7%), gasoline volatile sources (9.1%), and natural sources (6%), and the contribution rate of motor vehicle emission sources on polluted days increased by 4.6% compared with that on non-polluted days, indicating that the motor vehicle emission source was an important object of summer VOCs control in Yinchuan.

9.
Phytother Res ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120474

RESUMEN

Calycosin (Caly), a flavonoid compound, demonstrates a variety of beneficial properties. However, the specific mechanisms behind Caly's anticancer effects remain largely unexplored. Network pharmacology was used to explore the potential targets of Caly in renal cancer. Additionally, RNA-seq sequencing was used to detect changes in genes in renal cancer cells after Caly treatment. Validation was carried out through quantitative reverse transcription-PCR and Western blot analysis. The luciferase reporter assay was applied to pinpoint the interaction site between MAZ and HAS2. Furthermore, the immunoprecipitation assay was utilized to examine the ubiquitination and degradation of MAZ. In vivo experiments using cell line-derived xenograft mouse models were performed to assess Calycosin's impact on cancer growth. Network pharmacology research suggests Caly plays a role in promoting apoptosis and inhibiting cell adhesion in renal cancer. In vitro, Caly has been observed to suppress proliferation, colony formation, and metastasis of renal cancer cells while also triggering apoptosis. Additionally, it appears to diminish hyaluronic acid synthesis by downregulating HAS2 expression. MAZ is identified as a transcriptional regulator of HAS2 expression. Calycosin further facilitates the degradation of MAZ via the ubiquitin-proteasome pathway. Notably, Caly demonstrates efficacy in reducing the growth of renal cell carcinoma xenograft tumors in vivo. Our findings indicate that Caly suppresses the proliferation, metastasis, and progression of renal cell carcinoma through its action on the MAZ/HAS2 signaling pathway. Thus, Caly represents a promising therapeutic candidate for the treatment of renal cell carcinoma.

10.
J Transl Med ; 22(1): 748, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39118142

RESUMEN

BACKGROUND: Sjögren's Syndrome (SS) is a rare chronic autoimmune disorder primarily affecting adult females, characterized by chronic inflammation and salivary and lacrimal gland dysfunction. It is often associated with systemic lupus erythematosus, rheumatoid arthritis and kidney disease, which can lead to increased mortality. Early diagnosis is critical, but traditional methods for diagnosing SS, mainly through histopathological evaluation of salivary gland tissue, have limitations. METHODS: The study used 100 labial gland biopsy, creating whole-slide images (WSIs) for analysis. The proposed model, named Cell-tissue-graph-based pathological image analysis model (CTG-PAM) and based on graph theory, characterizes single-cell feature, cell-cell feature, and cell-tissue feature. Building upon these features, CTG-PAM achieves cellular-level classification, enabling lymphocyte recognition. Furthermore, it leverages connected component analysis techniques in the cell graph structure to perform SS diagnosis based on lymphocyte counts. FINDINGS: CTG-PAM outperforms traditional deep learning methods in diagnosing SS. Its area under the receiver operating characteristic curve (AUC) is 1.0 for the internal validation dataset and 0.8035 for the external test dataset. This indicates high accuracy. The sensitivity of CTG-PAM for the external dataset is 98.21%, while the accuracy is 93.75%. In comparison, the sensitivity and accuracy for traditional deep learning methods (ResNet-50) are lower. The study also shows that CTG-PAM's diagnostic accuracy is closer to skilled pathologists compared to beginners. INTERPRETATION: Our findings indicate that CTG-PAM is a reliable method for diagnosing SS. Additionally, CTG-PAM shows promise in enhancing the prognosis of SS patients and holds significant potential for the differential diagnosis of both non-neoplastic and neoplastic diseases. The AI model potentially extends its application to diagnosing immune cells in tumor microenvironments.


Asunto(s)
Síndrome de Sjögren , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/patología , Humanos , Femenino , Estudios de Cohortes , Curva ROC , Procesamiento de Imagen Asistido por Computador/métodos , Persona de Mediana Edad , Aprendizaje Profundo , Área Bajo la Curva , Adulto , Automatización
11.
Heliyon ; 10(15): e34321, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39144947

RESUMEN

Ultraviolet B (UVB) light exposure accelerates skin photoaging. Human adipose-derived stem cell exosomes (hADSC-Exos) and some antioxidants may have anti-photoaging effects. However, it is unknown whether the combination of hADSC-Exos and antioxidants plays a synergistic role in anti-photoaging. In cellular and 3D skin models, we showed that vitamin E (VE) and hADSC-Exos were optimal anti-photoaging combinations. In vivo, VE and hADSC-Exos increased skin tightening and elasticity in UVB-induced photoaging mice Combined treatment with VE and hADSC-Exos inhibited SIRT1/NF-κB pathway. These findings contribute to the understanding of hADSC-Exos in conjunction with other antioxidants, thereby providing valuable insights for the future pharmaceutical and cosmetic industries.

12.
Hortic Res ; 11(7): uhae149, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38994450

RESUMEN

Oomycete secretes a range of RxLR effectors into host cells to manipulate plant immunity by targeting proteins from several organelles. In this study, we report that chloroplast protein StFC-II is hijacked by a pathogen effector to enhance susceptibility. Phytophthora infestans RxLR effector Pi22922 is activated during the early stages of P. infestans colonization. Stable overexpression of Pi22922 in plants suppresses flg22-triggered reactive oxygen species (ROS) burst and enhances leaf colonization by P. infestans. A potato ferrochelatase 2 (FC-II, a nuclear-encoded chloroplast-targeted protein), a key enzyme for heme biosynthesis in chloroplast, was identified as a target of Pi22922 in the cytoplasm. The pathogenicity of Pi22922 in plants is partially dependent on FC-II. Overexpression of StFC-II decreases resistance of potato and Nicotiana benthamiana against P. infestans, and silencing of NbFC-II in N. benthamiana reduces P. infestans colonization. Overexpression of StFC-II increases heme content and reduces chlorophyll content and photosynthetic efficiency in potato leaves. Moreover, ROS accumulation both in chloroplast and cytoplasm is attenuated and defense-related genes are down-regulated in StFC-II overexpression transgenic potato and N. benthamiana leaves. Pi22922 inhibits E3 ubiquitin ligase StCHIP-mediated StFC-II degradation in the cytoplasm and promotes its accumulation in chloroplasts. In summary, this study characterizes a new mechanism that an oomycete RxLR effector suppresses host defenses by promoting StFC-II accumulation in chloroplasts, thereby compromising the host immunity and promoting susceptibility.

14.
J Neural Eng ; 21(4)2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39029477

RESUMEN

Objective. Monitoring the depth of anaesthesia (DOA) during surgery is of critical importance. However, during surgery electroencephalography (EEG) is usually subject to various disturbances that affect the accuracy of DOA. Therefore, accurately estimating noise in EEG and reliably assessing DOA remains an important challenge. In this paper, we proposed a signal quality index (SQI) network (SQINet) for assessing the EEG signal quality and a DOA network (DOANet) for analyzing EEG signals to precisely estimate DOA. The two networks are termed SQI-DOANet.Approach. The SQINet contained a shallow convolutional neural network to quickly determine the quality of the EEG signal. The DOANet comprised a feature extraction module for extracting features, a dual attention module for fusing multi-channel and multi-scale information, and a gated multilayer perceptron module for extracting temporal information. The performance of the SQI-DOANet model was validated by training and testing the model on the large VitalDB database, with the bispectral index (BIS) as the reference standard.Main results. The proposed DOANet yielded a Pearson correlation coefficient with the BIS score of 0.88 in the five-fold cross-validation, with a mean absolute error (MAE) of 4.81. The mean Pearson correlation coefficient of SQI-DOANet with the BIS score in the five-fold cross-validation was 0.82, with an MAE of 5.66.Significance. The SQI-DOANet model outperformed three compared methods. The proposed SQI-DOANet may be used as a new deep learning method for DOA estimation. The code of the SQI-DOANet will be made available publicly athttps://github.com/YuRui8879/SQI-DOANet.


Asunto(s)
Anestesia , Electroencefalografía , Redes Neurales de la Computación , Electroencefalografía/métodos , Electroencefalografía/normas , Humanos , Anestesia/métodos , Aprendizaje Profundo , Procesamiento de Señales Asistido por Computador
15.
Genes (Basel) ; 15(7)2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39062719

RESUMEN

Styrax japonicus is a medicinal and ornamental shrub belonging to the Styracaceae family. To explore the diversity and characteristics of the chloroplast genome of S. japonicus, we conducted sequencing and comparison of the chloroplast genomes of four naturally distributed S. japonicus. The results demonstrated that the four chloroplast genomes (157,914-157,962 bp) exhibited a typical quadripartite structure consisting of a large single copy (LSC) region, a small single copy (SSC) region, and a pair of reverse repeats (IRa and IRb), and the structure was highly conserved. DNA polymorphism analysis revealed that three coding genes (infA, psbK, and rpl33) and five intergene regions (petA-psbJ, trnC-petN, trnD-trnY, trnE-trnT, and trnY-trnE) were identified as mutation hotspots. These genetic fragments have the potential to be utilized as DNA barcodes for future identification purposes. When comparing the boundary genes, a small contraction was observed in the IR region of four S. japonicus. Selection pressure analysis indicated positive selection for ycf1 and ndhD. These findings collectively suggest the adaptive evolution of S. japonicus. The phylogenetic structure revealed conflicting relationships among several S. japonicus, indicating divergent evolutionary paths within this species. Our study concludes by uncovering the genetic traits of the chloroplast genome in the differentiation of S. japonicus variety, offering fresh perspectives on the evolutionary lineage of this species.


Asunto(s)
Evolución Molecular , Genoma del Cloroplasto , Filogenia , Cloroplastos/genética , Acanthaceae/genética , Polimorfismo Genético
16.
J Am Chem Soc ; 146(31): 21535-21545, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39056748

RESUMEN

Electrophilic addition of alkenes is a textbook reaction that plays a pivotal role in organic chemistry. In the past decades, catalytic asymmetric variants of this important type of reaction have witnessed great achievements by the development of novel catalytic systems. However, enantioselective aza-electrophilic additions of unactivated alkenes, which could provide a transformative strategy for the preparation of synthetically significant nitrogen-containing compounds, still remain a formidable challenge. Herein, we have developed unprecedented Au(I)/NHC-catalyzed asymmetric aza-electrophilic additions of unactivated 1,1-disubstituted styrenes by the utilization of readily available dialkyl azodicarboxylates as electrophilic nitrogen sources. Based on this approach, a series of transformations, including [2 + 2] cycloaddition, intermolecular 1,2-oxyamination, and several types of intramolecular hydrazination-induced cyclizations, have been realized. These transformations provide a previously unattainable platform for the divergent synthesis of hydrazine derivatives, which could also be converted to other nitrogen-containing chiral synthons. Experimental and computational studies support the idea that carbocation intermediates are involved in reaction pathways.

17.
Int J Mol Sci ; 25(13)2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-39000510

RESUMEN

Poplar coma, the fluff-like appendages of seeds originating from the differentiated surface cells of the placenta and funicle, aids in the long-distance dispersal of seeds in the spring. However, it also poses hazards to human safety and causes pollution in the surrounding environment. Unraveling the regulatory mechanisms governing the initiation and development of coma is essential for addressing this issue comprehensively. In this study, strand-specific RNA-seq was conducted at three distinct stages of coma development, revealing 1888 lncRNAs and 52,810 mRNAs. The expression profiles of lncRNAs and mRNAs during coma development were analyzed. Subsequently, potential target genes of lncRNAs were predicted through co-localization and co-expression analyses. Integrating various types of sequencing data, lncRNA-miRNA-TF regulatory networks related to the initiation of coma were constructed. Utilizing identified differentially expressed genes encoding kinesin and actin, lncRNA-miRNA-mRNA regulatory networks associated with the construction and arrangement of the coma cytoskeleton were established. Additionally, relying on differentially expressed genes encoding cellulose synthase, sucrose synthase, and expansin, lncRNA-miRNA-mRNA regulatory networks related to coma cell wall synthesis and remodeling were developed. This study not only enhances the comprehension of lncRNA but also provides novel insights into the molecular mechanisms governing the initiation and development of poplar coma.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Redes Reguladoras de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , MicroARNs , Populus , ARN Largo no Codificante , ARN Mensajero , Populus/genética , ARN Largo no Codificante/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , MicroARNs/genética , Perfilación de la Expresión Génica/métodos , Semillas/genética , Semillas/crecimiento & desarrollo
18.
Genes Dev ; 38(13-14): 614-630, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39038850

RESUMEN

The alternative lengthening of telomeres (ALT) pathway maintains telomere length in a significant fraction of cancers that are associated with poor clinical outcomes. A better understanding of ALT mechanisms is therefore necessary for developing new treatment strategies for ALT cancers. SUMO modification of telomere proteins contributes to the formation of ALT telomere-associated PML bodies (APBs), in which telomeres are clustered and DNA repair proteins are enriched to promote homology-directed telomere DNA synthesis in ALT. However, it is still unknown whether-and if so, how-SUMO supports ALT beyond APB formation. Here, we show that SUMO condensates that contain DNA repair proteins enable telomere maintenance in the absence of APBs. In PML knockout ALT cell lines that lack APBs, we found that SUMOylation is required for manifesting ALT features independent of PML and APBs. Chemically induced telomere targeting of SUMO produces condensate formation and ALT features in PML-null cells. This effect requires both SUMOylation and interactions between SUMO and SUMO interaction motifs (SIMs). Mechanistically, SUMO-induced effects are associated with the accumulation of DNA repair proteins, including Rad52, Rad51AP1, RPA, and BLM, at telomeres. Furthermore, Rad52 can undergo phase separation, enrich SUMO at telomeres, and promote telomere DNA synthesis in collaboration with the BLM helicase in a SUMO-dependent manner. Collectively, our findings suggest that SUMO condensate formation promotes collaboration among DNA repair factors to support ALT telomere maintenance without PML. Given the promising effects of SUMOylation inhibitors in cancer treatment, our findings suggest their potential use in perturbing telomere maintenance in ALT cancer cells.


Asunto(s)
Reparación del ADN , Proteína de la Leucemia Promielocítica , Sumoilación , Homeostasis del Telómero , Telómero , Humanos , Proteína de la Leucemia Promielocítica/metabolismo , Proteína de la Leucemia Promielocítica/genética , Telómero/metabolismo , Línea Celular Tumoral , Proteína SUMO-1/metabolismo , Proteína SUMO-1/genética , Proteína Recombinante y Reparadora de ADN Rad52/metabolismo , Proteína Recombinante y Reparadora de ADN Rad52/genética , Línea Celular , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/metabolismo , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/genética
19.
Int J Mol Sci ; 25(13)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-39000259

RESUMEN

Molecular breeding accelerates animal breeding and improves efficiency by utilizing genetic mutations. Structural variations (SVs), a significant source of genetic mutations, have a greater impact on phenotypic variation than SNPs. Understanding SV functional mechanisms and obtaining precise information are crucial for molecular breeding. In this study, association analysis revealed significant correlations between 198-bp SVs in the GSTA2 promoter region and abdominal fat weight, intramuscular fat content, and subcutaneous fat thickness in chickens. High expression of GSTA2 in adipose tissue was positively correlated with the abdominal fat percentage, and different genotypes of GSTA2 exhibited varied expression patterns in the liver. The 198-bp SVs regulate GSTA2 expression by binding to different transcription factors. Overexpression of GSTA2 promoted preadipocyte proliferation and differentiation, while interference had the opposite effect. Mechanistically, the 198-bp fragment contains binding sites for transcription factors such as C/EBPα that regulate GSTA2 expression and fat synthesis. These SVs are significantly associated with chicken fat traits, positively influencing preadipocyte development by regulating cell proliferation and differentiation. Our work provides compelling evidence for the use of 198-bp SVs in the GSTA2 promoter region as molecular markers for poultry breeding and offers new insights into the pivotal role of the GSTA2 gene in fat generation.


Asunto(s)
Adipogénesis , Pollos , Glutatión Transferasa , Regiones Promotoras Genéticas , Animales , Adipogénesis/genética , Pollos/genética , Pollos/crecimiento & desarrollo , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Adipocitos/metabolismo , Adipocitos/citología , Diferenciación Celular/genética , Proliferación Celular/genética , Regulación de la Expresión Génica , Tejido Adiposo/metabolismo
20.
Biochem Pharmacol ; 227: 116427, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39009095

RESUMEN

Neuropathic pain is a highly prevalent and refractory condition, yet its mechanism remains poorly understood. While NR1, the essential subunit of NMDA receptors, has long been recognized for its pivotal role in nociceptive transmission, its involvement in presynaptic stimulation is incompletely elucidated. Transcription factors can regulate the expression of both pro-nociceptive and analgesic factors. Our study shows that transcription factor TFAP2A was up-regulated in the dorsal root ganglion (DRG) neurons, satellite glial cells (SGCs), and Schwann cells following spinal nerve ligation (SNL). Intrathecal injection of siRNA targeting Tfap2a immediately or 7 days after SNL effectively alleviated SNL-induced pain hypersensitivity and reduced Tfap2a expression levels. Bioinformatics analysis revealed that TFAP2A may regulate the expression of the Grin1 gene, which encodes NR1. Dual-luciferase reporter assays confirmed TFAP2A's positive regulation of Grin1 expression. Notably, both Tfap2a and Grin1 were expressed in the primary SGCs and upregulated by lipopolysaccharides. The expression of Grin1 was also down-regulated in the DRG following Tfap2a knockdown. Furthermore, intrathecal injection of siRNA targeting Grin1 immediately or 7 days post-SNL effectively alleviated SNL-induced mechanical allodynia and thermal hyperalgesia. Finally, intrathecal Tfap2a siRNA alleviated SNL-induced neuronal hypersensitivity, and incubation of primary SGCs with Tfap2a siRNA decreased NMDA-induced upregulation of proinflammatory cytokines. Collectively, our study reveals the role of TFAP2A-Grin1 in regulating neuropathic pain in peripheral glia, offering a new strategy for the development of novel analgesics.


Asunto(s)
Ganglios Espinales , Neuralgia , Neuroglía , Receptores de N-Metil-D-Aspartato , Factor de Transcripción AP-2 , Animales , Neuralgia/metabolismo , Neuralgia/genética , Ganglios Espinales/metabolismo , Factor de Transcripción AP-2/genética , Factor de Transcripción AP-2/metabolismo , Masculino , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Neuroglía/metabolismo , Ratones , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Regulación de la Expresión Génica , Ratones Endogámicos C57BL , Ratas Sprague-Dawley , Hiperalgesia/metabolismo , Hiperalgesia/genética
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