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1.
ACS Appl Mater Interfaces ; 16(15): 19379-19390, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38568698

RESUMEN

Photodriven chiral catalysis is the combination of photocatalysis and chiral catalysis and is considered one of the cleanest and most efficient methods for the synthesis of chiral compounds or drugs. Furthermore, due to the potential metal contamination associated with most metal-based catalysts, metal-free chiral photocatalysts are ideal candidates. In this work, we demonstrate that metal-free chiral carbon dots (CDs) exhibit size-dependent enantioselective photocatalytic activity. Using serine as the raw material, chiral CDs with well-defined structures and average sizes of 2.22, 3.01, 3.70, 4.77, and 7.21 nm were synthesized using the electrochemical method. These chiral CDs possess size-dependent band gaps and exhibit photoresponsive enantioselective catalytic activity toward the oxidation of dihydroxyphenylalanine (DOPA). Under light-assisted conditions, chiral CDs (L72, 500 µg/mL) exhibit high selectivity (selectivity factor: 2.07) and maintain a certain level of catalytic activity (1.34 µM/min) even at a low temperature of 5 °C. The high catalytic activity of the chiral CDs arises from their photoelectrons reducing O2 to generate O2-, as the active oxygen species for DOPA oxidation. The high enantioselectivity of the chiral CDs is attributed to their differential adsorption capabilities toward DOPA enantiomers. This study provides a new approach for designing metal-free chiral photocatalysts with high enantioselectivity.

2.
Sci Adv ; 10(14): eadl4600, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38579006

RESUMEN

Quantifying the structural variants (SVs) in nonhuman primates could provide a niche to clarify the genetic backgrounds underlying human-specific traits, but such resource is largely lacking. Here, we report an accurate SV map in a population of 562 rhesus macaques, verified by in-house benchmarks of eight macaque genomes with long-read sequencing and another one with genome assembly. This map indicates stronger selective constrains on inversions at regulatory regions, suggesting a strategy for prioritizing them with the most important functions. Accordingly, we identified 75 human-specific inversions and prioritized them. The top-ranked inversions have substantially shaped the human transcriptome, through their dual effects of reconfiguring the ancestral genomic architecture and introducing regional mutation hotspots at the inverted regions. As a proof of concept, we linked APCDD1, located on one of these inversions and down-regulated specifically in humans, to neuronal maturation and cognitive ability. We thus highlight inversions in shaping the human uniqueness in brain development.


Asunto(s)
Genoma , Genómica , Animales , Humanos , Macaca mulatta , Encéfalo
3.
Int J Geriatr Psychiatry ; 39(3): e6076, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38488826

RESUMEN

OBJECTIVES: The herbs in Tao Hong Si Wu Decoction (THSWD) are beneficial in the treatment of cognitive impairment. However, the underlying mechanisms of THSWD in treating diabetes-associated cognitive dysfunction (DACD) are not entirely explored. This study is aimed to investigate the therapeutic effects of THSWD in DACD model rats and the underlying mechanism. METHODS: Ultra-high-phase liquid chromatography was employed to identify the main compounds contained in the THSWD extract. DACD rat model was induced by feeding with a high-sugar and high-fat diet and injecting streptozotocin (35 mg/kg). DACD rats were gavaged with THSWD for 1 week. The learning and memory abilities of the rats were measured by using the Morris water maze. Western blotting was used to detect the changes in DACD rat targets. Statistical methods were used to evaluate the correlation between proteins. RESULTS: The results show that THSWD effectively reduced the escape latency, hippocampal neuron damage, glycosylated hemoglobin, type A1C, and blood lipid levels in DACD rats. Furthermore, DACD rats showed significantly increased amyloid precursor protein, ß-secretase, Aß1-40 , Aß1-42 , Tau phosphorylation, and advanced glycation end products (AGEs) expression. However, THSWD treatment can reverse this phenomenon. CONCLUSIONS: THSWD can improve the learning and memory abilities of DACD rats by inhibiting the expression of AEGs-AGE receptors pathway, which provides an experimental basis for the clinical application of THSWD. In addition, the experiment combines pharmacological and statistical methods, which offers a new perspective for the study of Chinese herbal medicine.


Asunto(s)
Disfunción Cognitiva , Diabetes Mellitus , Medicamentos Herbarios Chinos , Humanos , Ratas , Animales , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Placa Amiloide , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología
4.
J Mater Chem B ; 12(9): 2346-2353, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38344921

RESUMEN

Due to the advantages of good aqueous dispersion and biocompatibility, carbon dots (CDs) are promising candidates for a wide range of applications in the biological field. Notably, CDs derived from biosafe organic precursors will contribute both new types of CDs and new bioactivities. Herein, metformin (MET), a first-line drug for the treatment of type II diabetes, was selected as an organic precursor to fabricate a new type of CDs, namely, semi-carbonized MET (MCDs). These MCDs derived from MET possess a completely new antibacterial activity against Staphylococcus aureus (SA) and Escherichia coli (E. coli) compared with that of MET and achieve complete antibacterial activity at 200 µg mL-1. The broad-spectrum antibacterial mechanism of MCDs involves two aspects. For the Gram-positive bacteria SA, MCDs mainly affect the transport of nutrients by adsorbing onto the surface of bacteria, thereby inhibiting bacterial growth. For the Gram-negative bacteria E. coli, MCDs can easily pass through their thin cell walls and stimulate the bacteria to produce excess ROS, eventually leading to the death of the bacteria. This work may open a new way for the future design and development of CDs prepared from biosafe organic precursors with specific functions.


Asunto(s)
Diabetes Mellitus Tipo 2 , Metformina , Infecciones Estafilocócicas , Humanos , Carbono/química , Escherichia coli , Metformina/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Bacterias , Staphylococcus aureus
5.
J Colloid Interface Sci ; 659: 687-696, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38211486

RESUMEN

It is highly desirable to design and construct chemical catalysts with high activity and specificity as the alternatives of natural enzymes for industrial application. Chiral carbon dots (CDs), possessing both the intrinsic enzyme-like activity and specific recognition ability, are one of good candidates for enzyme-like catalysts. However, their catalytic activity is far from that of natural enzymes and needs to be enhanced. In this work, the modulation of the chiral structure and catalytic activity of chiral CDs with intrinsic oxidase-like activity was implemented by manganese (Mn) doping. Under the light condition, chiral CDs (l-Ser-CDs and d-Ser-CDs) derived from chiral serine (Ser) show weak catalytic activity and low selectivity toward the oxidation of L type of dopamine (l-DOPA), whereas the Mn functionalized chiral CDs (l-Mn-CDs or d-Mn-CDs) exhibit 6.9 times higher in catalytic activity and 2.9 times in selectivity ratio (SR) than Ser-CDs. Mn-CDs involve two-path catalytic process, in which the photogenerated electrons could reduce O2 to O2- as the active species and the holes would oxidize DOPA directly. Moreover, doping of Mn enables the CDs to generate more O2-. Besides, l-Mn-CDs have higher catalytic activity than that of d-Mn-CDs (+54.2 %), and the chiral Mn-CDs have stronger selective adsorption capacity towards chiral DOPA than Ser-CDs. Our work provides a new method for designing and preparing novel chiral artificial enzymes.


Asunto(s)
Manganeso , Oxidorreductasas , Oxidorreductasas/química , Manganeso/química , Carbono/química , Oxidación-Reducción , Dihidroxifenilalanina
6.
Arch Toxicol ; 98(3): 849-863, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38180513

RESUMEN

Trophoblast cell syncytialization is essential for placental and fetal development. Abnormal trophoblast cell fusion leads to pregnancy pathologies, such as preeclampsia (PE), intrauterine growth restriction (IUGR), and miscarriage. 27-hydroxycholesterol (27-OHC) is the most abundant oxysterol in human peripheral blood synthesized by sterol 27-hydroxylase (CYP27A1) and is considered a critical mediator between hypercholesterolemia and a variety of related disorders. Gestational hypercholesterolemia was associated with spontaneous preterm delivery and low birth weight (LBW) in term infants, yet the mechanism is unclear. In this study, two trophoblast cell models and CD-1 mice were used to evaluate the effects of 27-OHC on trophoblast fusion during placenta development. Two different kinds of trophoblast cells received a dosage of 2.5, 5, or 10 uM 27-OHC. Three groups of pregnant mice were randomly assigned: control, full treatment (E0.5-E17.5), or late treatment (E13.5-E17.5). All mice received daily intraperitoneal injections of saline (control group) and 27-OHC (treatment group; 5.5 mg/kg). In vitro experiments, we found that 27-OHC inhibited trophoblast cell fusion in primary human trophoblasts (PHT) and forskolin (FSK)-induced BeWo cells. 27-OHC up-regulated the expression of the PI3K/AKT/mTOR signaling pathway-related proteins. Moreover, the PI3K inhibitor LY294002 rescued the inhibitory effect of 27-OHC. Inhibition of trophoblast cell fusion by 27-OHC was also observed in CD-1 mice. Furthermore, fetal weight and placental efficiency decreased and fetal blood vessel development was inhibited in pregnant mice treated with 27-OHC. This study was the first to prove that 27-OHC inhibits trophoblast cell fusion by Activating PI3K/AKT/mTOR signaling pathway. This study reveals a novel mechanism by which dyslipidemia during pregnancy results in adverse pregnancy outcomes.


Asunto(s)
Hidroxicolesteroles , Hipercolesterolemia , Placenta , Embarazo , Femenino , Humanos , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patología , Trofoblastos , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/metabolismo
7.
Neurol Res ; 46(2): 187-194, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37931016

RESUMEN

BACKGROUND: Infections of the central nervous system (CNS) are potentially life-threatening and can cause serious morbidity. We evaluated the clinical value of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis and explored the factors affecting the results of mNGS. METHODS: Patients with suspected cases of encephalitis or meningitis who presented in Northern Jiangsu People's Hospital from 1 March 2018 to 30 September 2022 were collected. Demographic, historical, and clinical information were obtained, and cerebrospinal fluid (CSF) samples were treated with mNGS. The pathogen was identified using National Center for Biotechnology Information (NCBI) GenBank sequence data. RESULTS: Ninety-six patients were screened and finally 90 subjects enrolled. Of the 90 enrolled cases, 67 (74.4%) were diagnosed with central nervous system infections, which included 48 cases (71.6%) of viral infection, 11 (12.2%) of bacterial infection, 5 (7.5%) of mycobacterium tuberculosis, 2 (3.0%) of fungal infection, and 1 (1.5%) of rickettsia infection. From these cases, mNGS identified 40 (44.4%) true-positive cases, 3 (3.3%) false-positive case, 22 (24.4%) true-negative cases, and 25 (27.8%) false-negative cases. The sensitivity and specificity of mNGS were 61.5% and 88%, respectively. mNGS of CSF could show a higher positive rate in patients with marked CSF abnormalities, including elevated protein concentrations and monocyte counts. CONCLUSION: mNGS of CSF is an effective method for detecting infectious encephalitis and meningitis, and the results should be analyzed combined with conventional microbiological testing results.


Asunto(s)
Encefalitis , Encefalitis Infecciosa , Meningitis , Humanos , Estudios Retrospectivos , Meningitis/diagnóstico , Encefalitis Infecciosa/diagnóstico , Encefalitis/diagnóstico , Sensibilidad y Especificidad , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
8.
Front Endocrinol (Lausanne) ; 14: 1295040, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38152136

RESUMEN

Background: The existing literature on the relationship of hyperparathyroidism with both blood counts and biochemical indicators primarily comprises observational studies, which have produced inconsistent findings. This study aimed to evaluate the causal relationship between hyperparathyroidism and blood counts and biochemical indicators. Methods: Mendelian randomization (MR) analyses were conducted to investigate the associations between hyperparathyroidism and the identified 55 blood counts and biochemical indicators. The genome-wide association study (GWAS) for hyperparathyroidism data was obtained from FinnGen, while the GWASs for the blood counts and biochemical indicators were sourced from the UK Biobank (UKBB). Results: The MR analysis using the inverse-variance weighted (IVW) method revealed potential causality between genetically predicted hyperparathyroidism and seven out of 55 blood counts and biochemical indicators. These markers include "Platelet count" (Beta = -0.041; 95% CI: -0.066, -0.016; p = 0.001), "Platelet distribution width (PDW)" (Beta = 0.031; 95% CI: 0.006, 0.056; p = 0.016), "Mean platelet volume (MPV)" (Beta = 0.043; 95% CI: 0.010, 0.076; p = 0.011), "Vitamin D" (Beta = -0.038; 95% CI: -0.063, -0.013; p = 0.003), "Calcium (Ca2+)" (Beta = 0.266; 95% CI: 0.022, 0.509; p = 0.033), "Phosphate" (Beta = -0.114; 95% CI: -0.214, -0.014; p = 0.025), and "Alkaline phosphatase (ALP)" (Beta = 0.030; 95% CI: 0.010, 0.049; p = 0.003). Conclusion: The findings of our study revealed a suggestive causal relationship between hyperparathyroidism and blood cell count as well as biochemical markers. This presents a novel perspective for further investigating the etiology and pathological mechanisms underlying hyperparathyroidism.


Asunto(s)
Estudio de Asociación del Genoma Completo , Hiperparatiroidismo , Humanos , Análisis de la Aleatorización Mendeliana , Recuento de Plaquetas , Fosfatasa Alcalina
9.
Stud Health Technol Inform ; 308: 11-19, 2023 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-38007720

RESUMEN

Pieris Japonica, belonging to the Rhododendron family, is known for its anti-insect and analgesic properties. Despite previous research, the components and antioxidant activity of Pieris Japonica extract remain unclear. This study aims to identify the optimal extraction process for Pieris Japonica, determine its components, and evaluate its antioxidant capacity. An L9 (34) orthogonal method was employed to optimize the Pieris Japonica extraction process, with the polyphenol content serving as the extraction efficiency index. The extracted components were identified by high-performance liquid chromatography-mass spectrometry (HPLC/MS-MS). Antioxidant activity was assessed via the DPPH test, ABTS radical scavenging test, and FRAP reduction ability test. The optimal extraction process involved soaking Pieris Japonica powder in 60% ethanol with a weight-to-volume ratio of 1:20 (g/mL), followed by eight hours of reflux at 50°C. Under these conditions, the total polyphenol content was 11.2 ± 0.6 mg/g. HPLC/MS-MS revealed that flavonoids were the primary components in the Pieris Japonica extract. The FRAP method determined the total antioxidant capacity to be 1.00 ± 0.05 µmol/mL, while the DPPH method showed a radical scavenging rate of 42.21 ± 4.02%, and the ABTS method yielded a 85.74% scavenging rate, indicating a strong antioxidant activity. The primary components of Pieris Japonica extract were flavonoids, and the extracted plant material exhibited potent antioxidant activity.


Asunto(s)
Antioxidantes , Polifenoles , Polifenoles/análisis , Antioxidantes/análisis , Extractos Vegetales/análisis , Extractos Vegetales/química , Flavonoides/análisis
10.
Front Genet ; 14: 1284554, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37928247

RESUMEN

RNA N6-melthyladenosine (m6A) can play an important role in regulation of various biological processes. Chicken ovary development is closely related to egg laying performance, which is a process primarily controlled by complex gene regulations. In this study, transcriptome-wide m6A methylation of the Wuhua yellow-feathered chicken ovaries before and after sexual maturation was profiled to identify the potential molecular mechanisms underlying chicken ovary development. The results indicated that m6A levels of mRNAs were altered dramatically during sexual maturity. A total of 1,476 differential m6A peaks were found between these two stages with 662 significantly upregulated methylation peaks and 814 downregulated methylation peaks after sexual maturation. A positive correlation was observed between the m6A peaks and gene expression levels, indicating that m6A may play an important role in regulation of chicken ovary development. Functional enrichment analysis indicated that apoptosis related pathways could be the key molecular regulatory pathway underlying the poor reproductive performance of Wuhua yellow-feathered chicken. Overall, the various pathways and corresponding candidate genes identified here could be useful to facilitate molecular design breeding for improving egg production performance in Chinese local chicken breed, and it might also contribute to the genetic resource protection of valuable avian species.

11.
Nat Commun ; 14(1): 5718, 2023 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-37714837

RESUMEN

Despite the accumulating evidence linking the development of Alzheimer's disease (AD) to the aggregation of Aß peptides and the emergence of Aß oligomers, the FDA has approved very few anti-aggregation-based therapies over the past several decades. Here, we report the discovery of an Aß peptide aggregation inhibitor: an ultra-small nanodot called C3N. C3N nanodots alleviate aggregation-induced neuron cytotoxicity, rescue neuronal death, and prevent neurite damage in vitro. Importantly, they reduce the global cerebral Aß peptides levels, particularly in fibrillar amyloid plaques, and restore synaptic loss in AD mice. Consequently, these C3N nanodots significantly ameliorate behavioral deficits of APP/PS1 double transgenic male AD mice. Moreover, analysis of critical tissues (e.g., heart, liver, spleen, lung, and kidney) display no obvious pathological damage, suggesting C3N nanodots are biologically safe. Finally, molecular dynamics simulations also reveal the inhibitory mechanisms of C3N nanodots in Aß peptides aggregation and its potential application against AD.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Nanopartículas , Animales , Masculino , Ratones , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/patología , Muerte Celular , Citoesqueleto , Ratones Transgénicos , Péptidos , Nanopartículas/uso terapéutico , Péptidos beta-Amiloides/química , Péptidos beta-Amiloides/metabolismo , Agregado de Proteínas/efectos de los fármacos
12.
Colloids Surf B Biointerfaces ; 230: 113492, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37556883

RESUMEN

Alcoholic gastric ulcer is a common acute gastric injury disease. The drugs currently used in clinical practice not only cannot fundamentally treat gastric injury, but also have serious side effects. There is an urgent demand for the discovery of a mild drug to treat alcoholic gastric ulcers. Herein, the green carbon dots derived from charred Atractylodes macrocephala (CAM-CDs) were acquired and have been proven to be safe and effective in alleviating alcoholic gastric ulcers at an inhibition rate up to 60%. CAM-CDs can markedly attenuate the gastric mucosa damage such as mucosal defect, bleeding and inflammatory cell infiltration by histopathological examination. Serum and tissue inflammatory cytokine measurements, as well as immunohistochemistry results, indicate that its mechanism of gastric mucosal protection may involve the reduction of IL-1ß and TNF-α by regulating inflammatory signaling pathway of the NF-κB/NLRP3 axis, as well as elevation of IL-10 levels. CAM-CDs also can reduce oxidative stress markers (MDA), increase PGE2 and mucin secretion (MUC5AC), and it simultaneously exerts slight inhibition of hydrogen potassium ATPase and pepsin activity to protect gastric mucosa, as well as increases the microbial diversity and regulates species composition of gut microbiota in rats with gastric ulcer. Our work provides a new perspective on utilizing carbon-based nanomaterials in the development of new mild drugs.


Asunto(s)
Atractylodes , Nanopartículas , Úlcera Gástrica , Ratas , Animales , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/patología , Úlcera Gástrica/prevención & control , Atractylodes/química , Atractylodes/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Transducción de Señal , Nanopartículas/uso terapéutico , Mucosa Gástrica/metabolismo
13.
Materials (Basel) ; 16(13)2023 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-37444893

RESUMEN

Cr3C2-modified NiCr-TiC composite coatings were prepared using the plasma spraying technique for different Cr3C2 contents on the microstructure and the properties of the Ni-based TiC cladding layer were investigated. The microstructures of the coatings were characterized using scanning electron microscopy, and the friction and wear performance of the coating was evaluated by the wear tests. The results revealed that the surfaces of the Cr3C2-modified NiCr-TiC composite coatings with varying Cr3C2 contents were dense and smooth. TiC was uniformly distributed throughout the entire coating, forming a gradient interface between the binder phase of the Ni-based alloy and the hard phase of TiC. At high temperatures, Cr3C2 decomposes, with some chromium diffusing and forming complex carbides around TiC, some chromium solubilizes with Fe, Ni, and other elements. An increase in chromium carbide content leads to an upward trend in hardness. The measured hardness of the coatings ranged from 600 to 850 HV3 and tended to increase with increasing Cr3C2 content. When the mass fraction of Cr3C2 reached 30%, the hardness increased to 850 HV3, and the cracks and defects were observed in the coating, resulting in a wear resistance decline.

14.
Inorg Chem ; 62(28): 10876-10880, 2023 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-37389937

RESUMEN

Single-crystal-to-single-crystal (SCSC) transformations provide more possibilities for phase transitions, which have attracted great attention in crystal engineering. In this paper, we report a series of reversible SCSC transformations between nanoscale two-dimensional layered double hydroxide (LDH) crystals and three-dimensional metal-organic framework crystals. They can proceed not only in solution systems but also on the surface of solid-state polyacrylonitrile films and fibers. Specifically, reversible SCSC transformations can be carried out between nanoscale ZIF-67 and Co-LDH. The Co-LDH nanomaterials displayed excellent oxygen evolution reaction performance. This work has good universality and scalability, which provides a novel avenue for the synthesis of crystal materials and is of great significance for the recycling of resources.

15.
Genome Biol ; 24(1): 155, 2023 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-37381036

RESUMEN

BACKGROUND: The ring-shaped cohesin complex is an important factor for the formation of chromatin loops and topologically associating domains (TADs) by loop extrusion. However, the regulation of association between cohesin and chromatin is poorly understood. In this study, we use super-resolution imaging to reveal the unique role of cohesin subunit RAD21 in cohesin loading and chromatin structure regulation. RESULTS: We directly visualize that up-regulation of RAD21 leads to excessive chromatin loop extrusion into a vermicelli-like morphology with RAD21 clustered into foci and excessively loaded cohesin bow-tying a TAD to form a beads-on-a-string-type pattern. In contrast, up-regulation of the other four cohesin subunits results in even distributions. Mechanistically, we identify that the essential role of RAD21 is attributed to the RAD21-loader interaction, which facilitates the cohesin loading process rather than increasing the abundance of cohesin complex upon up-regulation of RAD21. Furthermore, Hi-C and genomic analysis reveal how RAD21 up-regulation affects genome-wide higher-order chromatin structure. Accumulated contacts are shown at TAD corners while inter-TAD interactions increase after vermicelli formation. Importantly, we find that in breast cancer cells, the expression of RAD21 is aberrantly high with poor patient survival and RAD21 forms beads in the nucleus. Up-regulated RAD21 in HeLa cells leads to compartment switching and up-regulation of cancer-related genes. CONCLUSIONS: Our results provide key insights into the molecular mechanism by which RAD21 facilitates the cohesin loading process and provide an explanation to how cohesin and loader work cooperatively to promote chromatin extrusion, which has important implications in construction of three-dimensional genome organization.


Asunto(s)
Proteínas de Ciclo Celular , Proteínas Cromosómicas no Histona , Humanos , Células HeLa , Proteínas de Ciclo Celular/genética , Cromatina , Proteínas de Unión al ADN , Cohesinas
16.
Sci Rep ; 13(1): 8218, 2023 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-37217794

RESUMEN

Nasopharyngeal carcinoma (NPC) is a common head and neck malignant with a high incidence in Southern China. Genetic aberrations play a vital role in the pathogenesis, progression and prognosis of NPC. In the present study, we elucidated the underlying mechanism of FAS-AS1 and its genetic variation rs6586163 in NPC. We demonstrated that FAS-AS1 rs6586163 variant genotype carriers were associated with lower risk of NPC (CC vs. AA, OR = 0.645, P = 0.006) and better overall survival (AC + CC vs. AA, HR = 0.667, P = 0.030). Mechanically, rs6586163 increased the transcriptional activity of FAS-AS1 and contributed to ectopic overexpression of FAS-AS1 in NPC. rs6586163 also exhibited an eQTL trait and the genes affected by rs6586163 were enriched in apoptosis related signaling pathway. FAS-AS1 was downregulated in NPC tissues and over-expression of FAS-AS1 was associated with early clinical stage and better short-term treatment efficacy for NPC patients. Overexpression of FAS-AS1 inhibited NPC cell viability and promoted cell apoptosis. GSEA analysis of RNA-seq data suggested FAS-AS1 participate in mitochondria regulation and mRNA alternative splicing. Transmission electron microscopic examination verified that the mitochondria was swelled, the mitochondrial cristae was fragmented or disappeared, and their structures were destroyed in FAS-AS1 overexpressed cells. Furthermore, we identified HSP90AA1, CS, BCL2L1, SOD2 and PPARGC1A as the top 5 hub genes of FAS-AS1 regulated genes involved in mitochondria function. We also proved FAS-AS1 could affect Fas splicing isoform sFas/mFas expression ratio, and apoptotic protein expression, thus leading to increased apoptosis. Our study provided the first evidence that FAS-AS1 and its genetic polymorphism rs6586163 triggered apoptosis in NPC, which might have a potential as new biomarkers for NPC susceptibility and prognosis.


Asunto(s)
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , ARN Largo no Codificante , Humanos , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Variación Genética , Mitocondrias/genética , Mitocondrias/patología , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , ARN Largo no Codificante/genética
17.
Small ; 19(31): e2300883, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37029573

RESUMEN

Carbon dots (CDs) with good water solubility and biocompatibility have become a research hotspot in the nano-enzyme and biomedical field. However, the problems of low catalytic activity and ambiguous catalytic site of CDs as nanozymes still need to be addressed. In this work, CDs loaded with Cu single atoms are obtained through pyrolysis, and the coordination structure and surface functional groups are regulated by adjusting the pyrolysis temperature. CDs obtained at 300 °C (named Cu-CDs-300) have the most carboxyl content and Cu is coordinated in the form of CuN2 O2 , which can better decompose H2 O2 to produce free radical and is beneficial to catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). The vmax is 6.56*10-7  m s-1 , 6.56 times higher than that of horseradish peroxidase (HRP). Moreover, Cu-CDs-300 can effectively lead to CT26 apoptosis by generating much free radicals. This work demonstrates the synergistic effect of oxygen-containing functional groups and metal coordination structures on peroxide-like activity of CDs and provides new ideas for the design of clear active structure and high efficiency peroxide-like single atom CDs catalyst.

18.
Toxicol Appl Pharmacol ; 467: 116494, 2023 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-37001609

RESUMEN

Hydroxysafflor yellow A (HSYA), a chalcone glycoside, is a component of Carthamus tinctorius L. and exerts anti-inflammatory and antioxidative effects. However, the therapeutic effect and the underlying mechanism of HSYA on ulcerative colitis is unclear. This study aimed to investigate the unexplored protective effects and underlying mechanisms of HSYA on UC. In vitro analyses showed that HSYA reduced the secretion of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-6 and inhibited nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3)/gasdermin D (GSDMD)-mediated pyroptosis in lipopolysaccharide/ adenosine-5'-triphosphate (LPS/ATP)-stimulated macrophages. Gas chromatography-mass spectrometry (GC-MS) profiling of intracellular metabolites showed that HSYA reduced the increased levels of glucose, glucose 6-phosphate, and lactic acid, and inhibited the increased hexokinase 1 (HK1) expression caused by LPS/ATP stimulation. HK1 shRNA transfection further confirmed that HSYA inhibited the NLRP3/GSDMD-mediated pyroptosis via HK1 downregulation. In vivo analyses showed that HSYA drastically attenuated UC symptoms by relieving body weight loss, a decline in colon length, and inflammatory infiltration in colonic tissues induced by dextran sulfate sodium (DSS). HSYA also reduced the secretion of pro-inflammatory cytokines including IL-1ß, IL-6, TNF-α, and IL-18. Moreover, HSYA inhibited HK1/NLRP3/GSDMD-mediated pyroptosis in DSS-induced colitis mice. Finally, 16S rRNA sequencing analyses of gut microbiota revealed that HSYA reversed gut microbiota dysbiosis by reducing the abundance of Proteobacteria and increasing that of Bacteroidetes. This study demonstrated that HSYA not only exerted anti-inflammatory effects by inhibiting HK1/NLRP3/GSDMD and suppressing pyroptosis but also regulated gut microbiota in mice with DSS-induced colitis. Our findings provide new experimental evidence that HSYA might be a potential candidate for treating inflammatory bowel diseases.


Asunto(s)
Colitis , Microbioma Gastrointestinal , Animales , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Lipopolisacáridos/farmacología , Hexoquinasa , Interleucina-6 , Piroptosis , ARN Ribosómico 16S , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/prevención & control , Antiinflamatorios/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Adenosina Trifosfato/farmacología , Glucosa , Sulfato de Dextran/toxicidad , Ratones Endogámicos C57BL
19.
Dalton Trans ; 52(16): 5075-5084, 2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-36975039

RESUMEN

Transition metal chalcogenides (TMCs) have been widely explored and utilized in sodium-ion battery (SIB) anodes owing to their unique advantages, such as high theoretical specific capacity and low cost. However, their inherent defects, such as low electronic conductivity and severe volume expansion, seriously limit the further development of TMC-based anodes. Here, a novel composite material of CoSe2 nanoparticles (NPs) encapsulated in a dual one-dimensional (1D) carbon composite structure (CoSe2@CNTs/N-CNFs) was designed deliberately. Carbon nanotubes (CNTs) were grown in situ on the surface of carbon nanofibers (CNFs) with eco-friendly ethanol as the carbon source, while electrospun polyacrylonitrile (PAN) fibers were pyrolyzed to form nitrogen-doped nanofibers. It is noted that the wrapping with the composite carbon structure greatly improved the stability of CoSe2 NPs and solved its inherent defects as an anode material. When assembled into a half-cell, the CoSe2@CNTs/N-CNFs electrode exhibited outstanding sodium storage performance with a reversible specific capacity of 442 mA h g-1 after 100 cycles at 0.1 A g-1, as well as excellent rate performance, and the discharge specific capacity still reached 265 mA h g-1 even after 2000 cycles at a high current density of 5 A g-1. This study shows a new way to build a novel carbon substrate and TMC composite sodium storage material with low cost.

20.
Chem Commun (Camb) ; 59(15): 2153-2156, 2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36727577

RESUMEN

We propose a strategy to etch dopants to construct Mo2C with more unsaturated coordination of Mo atoms and lattice distortion for enhanced catalytic activity. It is more effective than doping and etching pure Mo2C and provides a novel strategy for the preparation of catalysts with high catalytic activity.

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