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1.
Biol Res ; 57(1): 36, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38822414

RESUMEN

BACKGROUND: Helicase for meiosis 1 (HFM1), a putative DNA helicase expressed in germ-line cells, has been reported to be closely associated with premature ovarian insufficiency (POI). However, the underlying molecular mechanism has not been clearly elucidated. The aim of this study was to investigate the function of HFM1 in the first meiotic prophase of mouse oocytes. RESULTS: The results suggested that the deficiency of HFM1 resulting in increased apoptosis and depletion of oocytes in mice, while the oocytes were arrested in the pachytene stage of the first meiotic prophase. In addition, impaired DNA double-strand break repair and disrupted synapsis were observed in the absence of HFM1. Further investigation revealed that knockout of HFM1 promoted ubiquitination and degradation of FUS protein mediated by FBXW11. Additionally, the depletion of HFM1 altered the intranuclear localization of FUS and regulated meiotic- and oocyte development-related genes in oocytes by modulating the expression of BRCA1. CONCLUSIONS: These findings elaborated that the critical role of HFM1 in orchestrating the regulation of DNA double-strand break repair and synapsis to ensure meiosis procession and primordial follicle formation. This study provided insights into the pathogenesis of POI and highlighted the importance of HFM1 in maintaining proper meiotic function in mouse oocytes.


Asunto(s)
Profase Meiótica I , Oocitos , Ubiquitinación , Animales , Oocitos/metabolismo , Profase Meiótica I/fisiología , Femenino , Ratones , Roturas del ADN de Doble Cadena , Proteína FUS de Unión a ARN/metabolismo , Proteína FUS de Unión a ARN/genética , Meiosis/fisiología , Reparación del ADN/fisiología , Ratones Noqueados , Apoptosis/fisiología
2.
J Org Chem ; 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38829824

RESUMEN

A cooperative Rh/achiral phosphoric acid-enabled [3+3] cycloaddition of in situ-generated carbonyl ylides with quinone monoimines has been developed. With the ability to build up the molecular complexity rapidly and efficiently, this method furnishes highly functionalized oxa-bridged benzofused dioxabicyclo[3.2.1]octane scaffolds bearing two quaternary centers in good to excellent yields under mild conditions. Moreover, the utility of the current method was demonstrated by gram-scale synthesis and elaboration of the products into various functionalized oxa-bridged heterocycles.

3.
ChemSusChem ; : e202400598, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38697954

RESUMEN

It has been known that plastics with undegradability and long half-times have caused serious environmental and ecological issues. Considering the devastating effects, the development of efficient plastic upcycling technologies with low energy consumption is absolutely imperative. Catalytic hydrogenolysis of single-use polyethylene over Ru-based catalysts to produce high-quality liquid fuel has been one of the current top priority strategies, but it is restricted by some tough challenges, such as the tendency towards methanation resulting from terminal C-C cleavage. Herein, we introduced Ru nanoparticles supported on hollow ZSM-5 zeolite (Ru/H-ZSM-5) for hydrocracking of high-density polyethylene (HDPE) under mild reaction conditions. The implication of experimental results is that the 1Ru/H-ZSM-5 (~1wt% Ru) acted as an effective and reusable bifunctional catalyst providing higher conversion rate (84.30%) and liquid fuel (C5-C21) yield (62.77%). Detailed characterization demonstrated that the optimal performance in hydrocracking of PE could be attributed to the moderate acidity and appropriate positively charged Ru species resulting from the metal-zeolite interaction. This work proposes a promising catalyst for plastic upcycling and reveals its structure-performance relationship, which has guiding significance for catalyst design to improve the yield of high-value liquid fuels.

4.
Water Res ; 257: 121719, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38728783

RESUMEN

Biological soil crusts (BSCs) are typical covers in arid and semiarid regions. The dissolved organic matter (DOM) of BSCs can be transported to various aquatic ecosystems by rainfall-runoff processes. However, the spatiotemporal variation in quality and quantity of DOM in runoff remains unclear. Herein, four kinds of runoff plots covered by four successional stages of BSCs were set up on slopes, including bare runoff plot (BR), cyanobacteria crust covered runoff plot (CR), mixed crust covered runoff plot (MIR), and moss crust covered runoff plot (MOR). The quantity and quality of DOM in runoff during rainfall was investigated based on the stimulated rainfall experiments combined with optical spectroscopy and ultra-high resolution mass spectrometry analyses. The results showed that the DOM concentrations (i.e., 0.30 to 45.25 mg L-1) in runoff followed the pattern of MOR>MIR>CR>BR, and they were exponentially decreased with rainfall duration. The DOM loss rate of BR (8.26 to 11.64 %) was significantly greater than those of CR, MIR, and MOR (0.84 to 3.22 %). Highly unsaturated compounds (HUCs), unsaturated aliphatic compounds (UACs), saturated compounds (SCs), and peptide-like compounds (PLCs) were the dominated compounds of the water extractable DOM from the original soils. Thereinto, PLCs and UACs were more easily leached into runoff during rainfall. The relatively intensity of HUCs in runoff generally decreased with rainfall duration, while the relatively intensities of UACs, PLCs, and SCs slightly increased with rainfall duration. These findings suggested that the DOM loss rate was effectively decreased with the successional of BSCs during rainfall; meanwhile, some labile compounds (e.g., PLCs and UACs) were transported into various aquatic ecosystems by rainfall-runoff processes.


Asunto(s)
Lluvia , Suelo , Suelo/química , Compuestos Orgánicos , Monitoreo del Ambiente/métodos , Movimientos del Agua
5.
Front Psychol ; 15: 1310343, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38756491

RESUMEN

As an important carrier of culture, poetry plays a significant role in deepening language learners' understanding of the target language culture as well as enhancing their language skills; however, the effect of the target language culture on language learners' enjoyment of poetry remains unclear. The study served as an attempt to shed light on the point of whether the target language culture has different effects on high- and low-level Chinese Arabic learners' fondness for Arabic poetry with the use of pictures related to Arabic culture and those not related to Arabic culture. In the current study, 40 Arabic learners (20 high-level and 20 low-level) scored the Arabic poem line based on their fondness for it after viewing two kinds of picture with electroencephalogram (EEG) recording. Frontal alpha asymmetry index as a correlate of approach and avoidance related motivation measured by EEG power in the alpha band (8-13 Hz) was calculated for examining whether the behavioral results of Arabic learners' fondness for poetry are in line with the results of changes in the related EEG components. Behavioral results illustrated that low-level subjects showed significantly less liking for Arabic poetry after viewing pictures related to Arabic culture compared to those not related to Arabic culture. The high-level subjects did not show a significant difference in the level of liking for Arabic poetry between the two cases. FAA results demonstrated that low-level subjects presented a significant avoidance-related responses to Arabic poetry after viewing pictures related to Arabic culture in comparison to viewing pictures not related to Arabic culture; while the FAA values did not differ significantly between the two cases in high-level subjects, which is in line with behavioral results. The findings of this research can benefit teachers in motivating students to learn poetry in foreign language curriculum and also contribute to the literature on the effect of target language culture on language learners' enjoyment of poetry.

6.
J Agric Food Chem ; 72(19): 10923-10935, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38691832

RESUMEN

This study aimed to explore the ameliorative effects and potential mechanisms of Huangshan Umbilicaria esculenta polysaccharide (UEP) in dextran sulfate sodium-induced acute ulcerative colitis (UC) and UC secondary liver injury (SLI). Results showed that UEP could ameliorate both colon and liver pathologic injuries, upregulate mouse intestinal tight junction proteins (TJs) and MUC2 expression, and reduce LPS exposure, thereby attenuating the effects of the gut-liver axis. Importantly, UEP significantly downregulated the secretion levels of TNF-α, IL-1ß, and IL-6 through inhibition of the NF-κB pathway and activated the Nrf2 signaling pathway to increase the expression levels of SOD and GSH-Px. In vitro, UEP inhibited the LPS-induced phosphorylation of NF-κB P65 and promoted nuclear translocation of Nrf2 in RAW264.7 cells. These results revealed that UEP ameliorated UC and SLI through NF-κB and Nrf2-mediated inflammation and oxidative stress. The study first investigated the anticolitis effect of UEP, suggesting its potential for the treatment of colitis and colitis-associated liver disease.


Asunto(s)
Colitis , Sulfato de Dextran , Factor 2 Relacionado con NF-E2 , FN-kappa B , Polisacáridos , Animales , Ratones , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/administración & dosificación , Sulfato de Dextran/efectos adversos , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Humanos , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Colitis/metabolismo , Células RAW 264.7 , FN-kappa B/metabolismo , FN-kappa B/genética , Ratones Endogámicos C57BL , Sustancias Protectoras/farmacología , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/química , Hígado/efectos de los fármacos , Hígado/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/inmunología , Estrés Oxidativo/efectos de los fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/inmunología , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-6/inmunología , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/inducido químicamente , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Mucina 2/genética , Mucina 2/metabolismo
7.
Se Pu ; 42(5): 452-457, 2024 Apr 08.
Artículo en Chino | MEDLINE | ID: mdl-38736388

RESUMEN

The applications of organic-amine desulfurization have steadily increased owing to its high efficiency, low cost, and low energy consumption. Different proportions of organic amines exert different effects on sulfur dioxide removal. Therefore, the accurate determination of different organic amines in the desulfurization solution is of great importance. The ion-chromatographic method for the detection of organic amines does not require a derivatization step, has simple pretreatment procedures, and allows for the simultaneous determination of many types of organic amines. In this study, a method based on ion chromatography was developed for the simultaneous determination of ethanolamine (MEA), diethylethanolamine (DEEA), n-methyldiethanolamine (MDEA), 2-amino-2-methyl-1-propanol (AMP), hydroxyethylethylenediamine (AEEA), piperazine (PZ), n-hydroxyethylpiperazine (HEPZ), and diethylenetriamine (DETA). The separation efficiency of the eight organic amines in different types of columns, leaching solutions, and column temperatures were compared. The determination was performed using an IonPac CS17 column with column temperature of 35 ℃ and gradient leaching with methyl sulfonic acid (MSA) solution via the inhibition conductance method. Samples of the desulfurization solution were analyzed using ultrapure water filtered through a 0.22 µm nylon microporous filter membrane and an OnGuard Ⅱ RP column; thus, the pretreatment steps are simple. The eight organic amines showed a good linear relationship within a certain concentration range, and the coefficient of determinations (R2) were greater than 0.998. The limits of detection (LODs) and quantification (LOQs) were determined from the mass concentrations of the organic amines corresponding to signal-to-noise ratios (S/N) of 3 and 10, respectively. LODs of 0.02-0.08 mg/L and LOQs of 0.07-0.27 mg/L were determined from a 1.0 µL sample injection. The actual recoveries ranged from 93.0% to 111%, and the relative standard deviations (RSDs, n=5) ranged from 0.31% to 1.2%. The results indicated that the proposed method has good accuracy and precision; thus, it is suitable for the determination of various organic amines in desulfurization solution.

8.
Biomol Biomed ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38733632

RESUMEN

Diabetic nephropathy (DN) is a severe complication of prolonged diabetes, impacting millions worldwide with an increasing incidence. This study investigates the role of tribbles pseudokinase 3 (TRIB3), a protein implicated in the progression of DN, focusing on its mechanisms underlying glomerular damage. Through analysis of the Gene Expression Omnibus (GEO) database, we identified TRIB3 among differentially expressed genes in streptozotocin (STZ)-treated C57BL/6J mice. Both in vitro and in vivo experiments were conducted to examine the effects of TRIB3 inhibition on high glucose (HG)-induced damage in podocytes and DN mouse models. The results demonstrated that TRIB3 inhibition reduced inflammatory responses and extracellular matrix (ECM) production in MPC5 cells, mediated by the downregulation of DNA damage-inducible transcript 3 (DDIT3) - a critical regulator of proinflammatory cytokine secretion and ECM synthesis. Inhibiting TRIB3 decreased inflammatory factors and ECM deposition in diabetic mice in vivo, confirming its pivotal role in DN pathogenesis. These findings indicate that TRIB3 and its interaction with DDIT3 contribute significantly to DN by promoting inflammatory cascades and ECM accumulation, presenting potential therapeutic targets for managing the disease.

9.
J Hazard Mater ; 473: 134610, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38776812

RESUMEN

Mg-K homeostasis is essential for plant response to abiotic stress, but its regulation remains largely unknown. MsWRKY44 cloned from alfalfa was highly expressed in leaves and petioles. Overexpression of it inhibited alfalfa growth, and promoted leaf senescence and alfalfa sensitivities to acid and Al stresses. The leaf tips, margins and interveins of old leaves occurred yellow spots in MsWRKY44-OE plants under pH4.5 and pH4.5 +Al conditions. Meanwhile, Mg-K homeostasis was substantially changed with reduction of K accumulation and increases of Mg as well as Al accumulation in shoots of MsWRKY44-OE plants. Further, MsWRKY44 was found to directly bind to the promoters of MsMGT7 and MsCIPK23, and positively activated their expression. Transiently overexpressed MsMGT7 and MsCIPK23 in tobacco leaves increased the Mg and Al accumulations but decreased K accumulation. These results revealed a novel regulatory module MsWRKY44-MsMGT7/MsCIPK23, which affects the transport and accumulation of Mg and K in shoots, and promotes alfalfa sensitivities to acid and Al stresses.

10.
Analyst ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38775334

RESUMEN

Urine provides an ideal source for disease biomarker discovery. High-adhesion contaminants such as urobilin, which are difficult to remove from urine, can severely interfere with urinary proteomic analysis. Here, we aimed to establish a strategy based on single-pot, solid-phase-enhanced sample preparation (SP3) technology to prepare samples for urinary proteomics analysis that almost completely eliminates the impact of urobilin. A systematic evaluation of the effects of two urinary protein precipitation methods, two types of protein lysis buffers, and different ratios of magnetic digestion beads on the identification and quantification of the microscale urinary proteome was conducted. Our results indicate that methanol-chloroform precipitation, coupled with efficient lysis facilitated by urea, and subsequent enzymatic digestion using a mix of hydrophilic and hydrophobic magnetic beads offers the best performance. Further applying this strategy to the urine of patients with benign prostatic hyperplasia, prostate cancer and healthy individuals, combined with a narrow window of data-independent acquisition, FGFR4, MYLK, ORM2, GOLM1, SPP1, CD55, CSF1, DLD and TIMP3 were identified as potential biomarkers to discriminate benign prostatic hyperplasia and prostate cancer patients.

11.
Nano Lett ; 24(20): 6183-6191, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38728596

RESUMEN

Two-dimensional (2D) materials are promising candidates for spintronic applications. Maintaining their atomically smooth interfaces during integration of ferromagnetic (FM) electrodes is crucial since conventional metal deposition tends to induce defects at the interfaces. Meanwhile, the difficulties in picking up FM metals with strong adhesion and in achieving conductance match between FM electrodes and spin transport channels make it challenging to fabricate high-quality 2D spintronic devices using metal transfer techniques. Here, we report a solvent-free magnetic electrode transfer technique that employs a graphene layer to assist in the transfer of FM metals. It also serves as part of the FM electrode after transfer for optimizing spin injection, which enables the realization of spin valves with excellent performance based on various 2D materials. In addition to two-terminal devices, we demonstrate that the technique is applicable for four-terminal spin valves with nonlocal geometry. Our results provide a promising future of realizing 2D spintronic applications using the developed magnetic electrode transfer technique.

12.
ChemMedChem ; : e202400021, 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38735844

RESUMEN

Cervical cancer seriously affects the health of women worldwide. Persistent infection of high-risk HPV (Human Papilloma Virus) can lead to cervical cancer. There is a great need for timely and efficient screening methods for cervical cancer. The current screening methods for cervical cancer are mainly based on cervical cytology and HPV testing. Cervical  cytology is made of Pap smear and liquid-based cytology, while HPV testing is based on immunological and nucleic acid level detection methods.  This review introduces cervical cancer screening methods based on cytology and human papillomavirus testing in detail. The advantages and limitations of the screening methods are also summarized and compared.

13.
Phytomedicine ; 130: 155757, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38805781

RESUMEN

BACKGROUND: In acute kidney injury (AKI), ferroptosis is the main mechanism of cell death in the renal tubular epithelium. Baicalein, a traditional Chinese medicine monomer, plays a protective role in various kidney diseases; however, the effect of baicalein on ferroptosis in AKI still needs further exploration. PURPOSE: In this study, we explored the role of baicalein and its specific mechanism in mediating ferroptosis in cisplatin-induced AKI. METHODS: We used a cisplatin-induced AKI model to study the effects of baicalein on renal tissue and tubular epithelial cell injury. The effects of baicalein on tubular epithelial cell ferroptosis were detected in cisplatin-induced AKI and further verified by folic acid-induced AKI. The Swiss Target Prediction online database was used to predict the possible mechanism by which baicalein regulates ferroptosis, and the specific target proteins were further verified. Molecular docking and SPR were used to further determine the binding potential of baicalein to the target protein. Finally, RNA interference (RNAi) technology and enzymatic inhibition were used to determine whether baicalein regulates ferroptosis through target proteins. RESULTS: Baicalein alleviated cisplatin- and folic acid-induced renal dysfunction and pathological damage and improved cisplatin-induced HK2 cell injury. Mechanistically, baicalein reduced the expression of 12-lipoxygenase (ALOX12), which inhibits phospholipid peroxidation and ferroptosis in AKI. Molecular docking and SPR demonstrated direct binding between baicalein and ALOX12. Finally, we found that silencing ALOX12 had a regulatory effect similar to that of baicalein. Comparable results were also obtained with the ALOX12 inhibitor ML355. CONCLUSION: This was the first study to confirm that baicalein regulates ferroptosis both in vitro and in vivo in cisplatin-induced AKI and to verify the regulatory effect of baicalein in folic acid-induced AKI. Our results reveal the critical role of ALOX12 in kidney damage and ferroptosis caused by cisplatin and emphasize the regulatory effect of baicalein on renal tubular epithelial cell ferroptosis mediated by ALOX12. Baicalein is an effective drug for treating AKI, and ALOX12 is a potential drug target.

14.
Adv Sci (Weinh) ; : e2306890, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816931

RESUMEN

In spite of recent advances in the field of undernutrition, current dietary therapy relying on the supply of high protein high calorie formulas is still plagued with transient recovery of impaired organs resulting in significant relapse of cases. This is partly attributed to the inadequacy of current research models in recapitulating clinical undernutrition for mechanistic exploration. Using 1636 Macaca fascicularis monkeys, a human-relevant criterion for determining undernutrition weight-for-age z-score (WAZ), with a cutoff point of ≤ -1.83 is established as the benchmark for identifying undernourished nonhuman primates (U-NHPs). In U-NHPs, pathological anomalies in multi-organs are revealed. In particular, severe dysregulation of hepatic lipid metabolism characterized by impaired fatty acid oxidation due to mitochondria dysfunction, but unlikely peroxisome disorder, is identified as the anchor metabolic aberration in U-NHPs. Mitochondria dysfunction is typified by reduced mito-number, accumulated long-chain fatty acids, and disruption of OXPHOS complexes. Soy peptide-treated U-NHPs increase in WAZ scores, in addition to attenuated mitochondria dysfunction and restored OXPHOS complex levels. Herein, innovative criteria for identifying U-NHPs are developed, and unknown molecular mechanisms of undernutrition are revealed hitherto, and it is further proved that soypeptide supplementation reprogramed mitochondrial function to re-establish lipid metabolism balance and mitigated undernutrition.

15.
Int J Mol Sci ; 25(10)2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38791317

RESUMEN

The myostatin (MSTN) gene also regulates the developmental balance of skeletal muscle after birth, and has long been linked to age-related muscle wasting. Many rodent studies have shown a correlation between MSTN and age-related diseases. It is unclear how MSTN and age-associated muscle loss in other animals are related. In this study, we utilized MSTN gene-edited bovine skeletal muscle cells to investigate the mechanisms relating to MSTN and muscle cell senescence. The expression of MSTN was higher in older individuals than in younger individuals. We obtained consecutively passaged senescent cells and performed senescence index assays and transcriptome sequencing. We found that senescence hallmarks and the senescence-associated secretory phenotype (SASP) were decreased in long-term-cultured myostatin inactivated (MT-KO) bovine skeletal muscle cells (bSMCs). Using cell signaling profiling, MSTN was shown to regulate the SASP, predominantly through the cycle GMP-AMP synthase-stimulator of antiviral genes (cGAS-STING) pathway. An in-depth investigation by chromatin immunoprecipitation (ChIP) analysis revealed that MSTN influenced three prime repair exonuclease 1 (TREX1) expression through the SMAD2/3 complex. The downregulation of MSTN contributed to the activation of the MSTN-SMAD2/3-TREX1 signaling axis, influencing the secretion of SASP, and consequently delaying the senescence of bSMCs. This study provided valuable new insight into the role of MSTN in cell senescence in large animals.


Asunto(s)
Senescencia Celular , Miostatina , Animales , Miostatina/genética , Miostatina/metabolismo , Bovinos , Senescencia Celular/genética , Exodesoxirribonucleasas/metabolismo , Exodesoxirribonucleasas/genética , Transducción de Señal , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Células Cultivadas
16.
Heliyon ; 10(9): e30330, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38726177

RESUMEN

Background: Colon cancer (CC) stem cells can self-renew as well as expand, thereby promoting tumor progression and conferring resistance to chemotherapeutic agents. The acetyltransferase NAT10 mediates N4-acetylcytidine (ac4C) modification, which in turn drives tumorigenesis, metastasis, stemness properties maintenance, and cell fate decisions. Nonetheless, the specific involvement of ac4C modification mediated by NAT10 in regulating stemness and chemosensitivity in CC remains undetermined. Methods: The levels of NAT10 in normal colon and chemoresistant CC tissues were determined utilizing quantitative real-time polymerase chain reaction alongside immunohistochemistry. Assessing cancer cell stemness and chemosensitivity was conducted by various methods including spheroid and colony formation, western blotting, and flow cytometry. RNA-Seq was used to identify target genes, and RNA immunoprecipitation analysis was used to explore the potential mechanisms. Results: We observed NAT10 overexpression and increased ac4C modification levels in chemoresistant CC tissues. The in vivo and in vitro analysis findings suggested that NAT10 promoted CC cell stemness while suppressing their chemosensitivity. Conversely, Remodelin, a NAT10-specific inhibitor, enhanced CC cell chemosensitivity. Mechanistically, NAT10 increased the level of NANOGP8 ac4C modification and promoted NANOGP8 mRNA stability. Conclusions: NAT10 promotes the maintenance of stemness and chemoresistance in CC cells by augmenting the mRNA stability of NANOGP8. The inhibition of NAT10 via Remodelin improves chemotherapeutic efficacy and impedes CC progression.

17.
J Psychiatry Neurosci ; 49(3): E192-E207, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38816029

RESUMEN

BACKGROUND: Recent studies have identified empathy deficit as a core impairment and diagnostic criterion for people with autism spectrum disorders; however, the improvement of empathy focuses primarily on behavioural interventions without the target regulation. We sought to compare brain regions associated with empathy-like behaviours of fear and pain, and to explore the role of the oxytocin-oxytocin receptor system in fear empathy. METHODS: We used C57BL mice to establish 2 models of fear empathy and pain empathy. We employed immunofluorescence histochemical techniques to observe the expression of c-Fos throughout the entire brain and subsequently quantified the number of c-Fos-positive cells in different brain regions. Furthermore, we employed chemogenetic technology to selectively manipulate these neurons in Oxt-Cre-/+ mice to identify the role of oxytocin in this process. RESULTS: The regions activated by fear empathy were the anterior cingulate cortex, basolateral amygdala, nucleus accumbens, paraventricular nucleus (PVN), lateral habenula, and ventral and dorsal hippocampus. The regions activated by pain empathy were the anterior cingulate cortex, basolateral amygdala, nucleus accumbens, and lateral habenula. We found that increasing the activity of oxytocin neurons in the PVN region enhanced the response to fear empathy. This enhancement may be mediated through oxytocin receptors. LIMITATIONS: This study included only male animals, which restricts the broader interpretation of the findings. Further investigations on circuit function need to be conducted. CONCLUSION: The brain regions implicated in the regulation of fear and pain empathy exhibit distinctions; the activity of PVN neurons was positively correlated with empathic behaviour in mice. These findings highlight the role of the PVN oxytocin pathway in regulating fear empathy and suggest the importance of oxytocin signalling in mediating empathetic responses.


Asunto(s)
Empatía , Miedo , Ratones Endogámicos C57BL , Neuronas , Oxitocina , Núcleo Hipotalámico Paraventricular , Animales , Oxitocina/metabolismo , Masculino , Núcleo Hipotalámico Paraventricular/metabolismo , Miedo/fisiología , Empatía/fisiología , Neuronas/metabolismo , Ratones , Receptores de Oxitocina/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Dolor/fisiopatología , Dolor/psicología , Ratones Transgénicos
18.
Ann Hematol ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38802593

RESUMEN

Acute myeloid leukemia (AML) with t(8;21) (q22;q22), which forms RUNX1::RUNX1T1 fusion gene, is classified as a favorable-risk group. However, the presence of mutations in KIT exon 17 results in an adverse prognosis in this group. Avapritinib, a novel tyrosine kinase inhibitor, was designed to target KIT mutation. We report a retrospective study of four pediatric patients with AML with t(8:21) and KIT exon 17 mutation who were treated with avapritinib, three of them failed to demethylate drugs and donor lymphocyte infusion targeting RUNX1::RUNX1T1-positivity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). So far, all patients with RUNX1::RUNX1T1 positivity had turned negative after 1, 9, 7, 2 months of avapritinib treatment. The common adverse effect of avapritinib is neutropenia, which is well-tolerated. This case series indicates that avapritinib may be effective and safe for preemptive treatment of children with AML with t(8;21) and KIT mutation after allo-HSCT, providing a treatment option for preventing relapse after allo-HSCT.

19.
Discov Med ; 36(184): 936-945, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38798253

RESUMEN

BACKGROUND: Inflammation is a key pathological process in bacterial meningitis, and the transforming growth factor-beta-activated kinase 1 (TAK1)/nuclear factor-kappa B (NF-κB) pathway is implicated in the activation of microglia and the production of inflammatory factors. Interleukin (IL)-10 is an anti-inflammatory cytokine acting in an autocrine fashion in macrophages to limit inflammatory responses by decreasing the production of pro-inflammatory cytokines. This paper investigates how IL-10 can inhibit microglia activation and reduce the inflammatory response of nervous system diseases. METHODS: This study used a pneumococcal-induced in Pneumococcal meningitis (PM) C57BL/6 mice and BV-2 cells model of microglial activation, assessing the effects of IL-10 on the TAK1/NF-κB pathway. The impact of IL-10 on microglial autophagy was investigated through western blot and immunofluorescence. The effects of IL-10 were evaluated by examining cellular activation markers and the activity of molecular signaling pathways (such as phosphorylation levels of TAK1 and NF-κB). RESULTS: Pneumococcus induced the activation of microglia and reduced IL-10. IL-10 inhibited the TAK1/NF-κB pathway, reducing the pneumococcal-induced inflammatory response in microglia. IL-10 ameliorated pneumococcal infection-induced microglial injury by inhibiting autophagy. Animal experiment results also showed that IL-10 inhibited inflammation and autophagy during Pneumococcal meningitis in mice. CONCLUSION: Our study demonstrates that IL-10 reduces the inflammatory response of microglia by inhibiting the TAK1/NF-κB pathway. Additionally, IL-10 ameliorates pneumococcal infection-induced microglial injury by inhibiting the process of autophagy. These results provide a new theoretical basis and offer new insights for developing strategies to treat bacterial meningitis.


Asunto(s)
Interleucina-10 , Quinasas Quinasa Quinasa PAM , Meningitis Neumocócica , Ratones Endogámicos C57BL , Microglía , FN-kappa B , Animales , Interleucina-10/metabolismo , Microglía/metabolismo , Microglía/efectos de los fármacos , Microglía/patología , Ratones , Meningitis Neumocócica/tratamiento farmacológico , Meningitis Neumocócica/inmunología , Meningitis Neumocócica/patología , FN-kappa B/metabolismo , Quinasas Quinasa Quinasa PAM/metabolismo , Quinasas Quinasa Quinasa PAM/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Inflamación/patología , Autofagia/efectos de los fármacos , Modelos Animales de Enfermedad , Línea Celular , Streptococcus pneumoniae
20.
Ying Yong Sheng Tai Xue Bao ; 35(3): 739-748, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38646762

RESUMEN

Biological soil crust (biocrust) is widely distributed on the Loess Plateau and plays multiple roles in regulating ecosystem stability and multifunctionality. Few reports are available on the distribution characteristics of biocrust in this region, which limits the assessment of its ecological functions. Based on 388 sampling points in different precipitation zones on the Loess Plateau from 2009 to 2020, we analyzed the coverage, composition, and influencing factors of biocrust across different durations since land abandonment, precipitation levels, topography (slope aspect and position), and utilization of abandoned slopelands (shrubland, forest, and grassland). On this base, with the assistance of machine learning and spatial modeling methods, we generated a distribution map of biocrust and its composition at a resolution of 250 m × 250 m, and analyzed the spatial distribution of biocrust on the Loess Plateau. The results showed that the average biocrust coverage in the woodlands and grasslands was 47.3%, of which cyanobacterial crust accounted for 25.5%, moss crust 19.7%, and lichen crust 2.1%. There were significant temporal and spatial variations. Temporally, the coverage of biocrust in specific regions fluctuated with the extension of the abandoned durations and coverage of cyanobacterial crust, while moss crust showed a reverse pattern. In addition, the coverage of biocrust in the wet season was slightly higher than that in the dry season within a year. Spatially, the coverage of biocrusts on the sandy lands area on the Loess Plateau was higher and dominated by cyanobacterial crusts, while the coverage was lower in the hilly and gully area. Precipitation and utilization of abandoned land were the major factors driving biocrust coverage and composition, while slope direction and position did not show obvious effect. In addition, soil organic carbon content, pH, and texture were related to the distribution of biocrust. This study uncovered the spatial and temporal variability of biocrust distribution, which might provide important data support for the research and management of biocrust in the Loess Plateau region.


Asunto(s)
Ecosistema , Bosques , Líquenes , Suelo , Análisis Espacio-Temporal , China , Suelo/química , Líquenes/crecimiento & desarrollo , Pradera , Cianobacterias/crecimiento & desarrollo , Microbiología del Suelo , Altitud , Monitoreo del Ambiente , Briófitas/crecimiento & desarrollo , Árboles/crecimiento & desarrollo
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