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1.
J Am Chem Soc ; 146(19): 13236-13246, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38701635

RESUMO

Fluids under extreme confinement show characteristics significantly different from those of their bulk counterpart. This work focuses on water confined within the complex cavities of highly hydrophobic metal-organic frameworks (MOFs) at high pressures. A combination of high-pressure intrusion-extrusion experiments with molecular dynamic simulations and synchrotron data reveals that supercritical transition for MOF-confined water takes place at a much lower temperature than in bulk water, ∼250 K below the reference values. This large shifting of the critical temperature (Tc) is attributed to the very large density of confined water vapor in the peculiar geometry and chemistry of the cavities of Cu2tebpz (tebpz = 3,3',5,5'-tetraethyl-4,4'-bipyrazolate) hydrophobic MOF. This is the first time the shift of Tc is investigated for water confined within highly hydrophobic nanoporous materials, which explains why such a large reduction of the critical temperature was never reported before, neither experimentally nor computationally.

2.
Small ; : e2402173, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39113337

RESUMO

Liquid porosimetry experiments reveal a peculiar trend of the intrusion pressure of water in hydrophobic Cu2(3,3',5,5'-tetraethyl-4,4'-bipyrazolate) MOF. At lower temperature (T) range, the intrusion pressure (Pi) increases with T. For higher T values, Pi first reaches a maximum and then decreases. This is at odds with the Young-Laplace law, which for systems showing a continuous decrease of contact angle with T predicts a corresponding reduction of the intrusion pressure. Though the Young-Laplace law is not expected to provide quantitative predictions at the subnanoscale of Cu2(tebpz) pores, the physical intuition suggests that to a reduction of their hydrophobicity corresponds a reduction of the Pi. Molecular dynamics simulations and sychrothron experiments allowed to clarify the mechanism of the peculiar trend of Pi with T. At increasing temperatures the vapor density within the MOF' pores grows significantly, bringing the corresponding partial pressure to ≈5 MPa. This pressure, which is consistent with the shift of Pi observed in liquid porosimetry, represents a threshold to be overcame before intrusion takes place. Beyond some value of temperature, the phenomenon of reduction of hydrophobicity (and water surface tension) dominated over the opposite effect of increase of vapor pressure and Pi inverts its trend with T.

3.
J Transl Med ; 22(1): 490, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38790013

RESUMO

N6-methyladenosine (m6A) stands as the most prevalent modified form of RNA in eukaryotes, pivotal in various biological processes such as regulating RNA stability, translation, and transcription. All members within the YT521-B homology (YTH) gene family are categorized as m6A reading proteins, capable of identifying and binding m6A modifications on RNA, thereby regulating RNA metabolism and functioning across diverse physiological processes. YTH domain-containing 2 (YTHDC2), identified as the latest member of the YTH family, has only recently started to emerge for its biological function. Numerous studies have underscored the significance of YTHDC2 in human physiology, highlighting its involvement in both tumor progression and non-tumor diseases. Consequently, this review aims to further elucidate the pathological mechanisms of YTHDC2 by summarizing its functions and roles in tumors and other diseases, with a particular focus on its downstream molecular targets and signaling pathways.


Assuntos
Adenosina , Neoplasias , Proteínas de Ligação a RNA , Humanos , Adenosina/análogos & derivados , Adenosina/metabolismo , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/patologia , Proteínas de Ligação a RNA/metabolismo , Animais , Doença , Transdução de Sinais , RNA Helicases
4.
Inorg Chem ; 63(2): 1378-1387, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38164710

RESUMO

The zero-valent iron (ZVI) has attracted increasing attention due to the enhanced reactivity of ZVI to uranium wastewater. However, ZVI practical application is hampered due to its susceptibility to oxidation and the formation of passivation layers during storage and in situ restoration. To address these issues, we used a biosulfuration approach to modify ZVI for application in uranium ore wastewater treatment. A series of physicochemical characterization tools and photoelectronic analyses showed that BS-ZVI considerably increased carrier separation efficiency and visible light absorption capacity, resulting in a significant photoassisted enhancement effect on uranium extraction. Accordingly, the uranium removal efficiency of BS-ZVI reached 91% within 60 min, and its maximum adsorption capacity was 336.3 mg/g. By analyzing the mechanism, the improved U(VI) removal performance was mostly responsible on the dissolution of the passivation layer on the surface of ZVI, the generation of Fe(II) and FeS, and the important role of Shewanella putrefaciens extracellular polymers (EPS). Overall, the BS-ZVI biohybrid merges with the high activity of ZVI, bio-FeS, and self-regeneration ability of bacteria, expanding a promising new approach for sustainable treatment of uranium mine wastewater.

5.
World J Surg ; 48(1): 86-96, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38686746

RESUMO

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMN) are very rare, accounting for approximately 0.2%-0.5% of gastrointestinal tumors. We conducted a multicenter retrospective study to explore the impact of different surgical procedures combined with HIPEC on the short-term outcomes and long-term survival of patients. METHODS: We retrospectively analyzed the clinicopathological data of 91 LAMN perforation patients from 9 teaching hospitals over a 10-year period, and divided them into HIPEC group and non-HIPEC group based on whether or not underwent HIPEC. RESULTS: Of the 91 patients with LAMN, 52 were in the HIPEC group and 39 in the non-HIPEC group. The Kaplan-Meier method predicted that 52 patients in the HIPEC group had 5- and 10-year overall survival rates of 82.7% and 76.9%, respectively, compared with predicted survival rates of 51.3% and 46.2% for the 39 patients in the non-HIPEC group, with a statistically significant difference between the two groups (χ2 = 10.622, p = 0.001; χ2 = 10.995, p = 0.001). Compared to the 5-year and 10-year relapse-free survival rates of 75.0% and 65.4% in the HIPEC group, respectively, the 5-year and 10-year relapse-free survival rates of 48.7% and 46.2% in the non-HIPEC group were significant different between the two outcomes (χ2 = 8.063, p = 0.005; χ2 = 6.775, p = 0.009). The incidence of postoperative electrolyte disturbances and hypoalbuminemia was significantly higher in the HIPEC group than in the non-HIPEC group (p = 0.023; p = 0.044). CONCLUSIONS: This study shows that surgery combined with HIPEC can significantly improve 5-year and 10-year overall survival rates and relapse-free survival rates of LAMN perforation patients, without affecting their short-term clinical outcomes.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias do Apêndice , Quimioterapia Intraperitoneal Hipertérmica , Humanos , Estudos Retrospectivos , Masculino , Feminino , Neoplasias do Apêndice/terapia , Neoplasias do Apêndice/mortalidade , Neoplasias do Apêndice/patologia , Pessoa de Meia-Idade , Adulto , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Idoso , Terapia Combinada , Resultado do Tratamento , Taxa de Sobrevida , Gradação de Tumores , Perfuração Intestinal/etiologia , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/mortalidade
6.
J Nanobiotechnology ; 22(1): 468, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39103846

RESUMO

Ulcerative colitis (UC) is a challenging inflammatory gastrointestinal disorder, whose therapies encounter limitations in overcoming insufficient colonic retention and rapid systemic clearance. In this study, we report an innovative polymeric prodrug nanoformulation for targeted UC treatment through sustained 5-aminosalicylic acid (5-ASA) delivery. Amphiphilic polymer-based 13.5 nm micelles were engineered to incorporate azo-linked 5-ASA prodrug motifs, enabling cleavage via colonic azoreductases. In vitro, micelles exhibited excellent stability under gastric/intestinal conditions while demonstrating controlled 5-ASA release over 24 h in colonic fluids. Orally administered micelles revealed prolonged 24-h retention and a high accumulation within inflamed murine colonic tissue. At an approximately 60% dose reduction from those most advanced recent studies, the platform halted DSS colitis progression and outperformed standard 5-ASA therapy through a 77-97% suppression of inflammatory markers. Histological analysis confirmed intact colon morphology and restored barrier protein expression. This integrated prodrug nanoformulation addresses limitations in colon-targeted UC therapy through localized bioactivation and tailored pharmacokinetics, suggesting the potential of nanotechnology-guided precision delivery to transform disease management.


Assuntos
Colite , Colo , Preparações de Ação Retardada , Mesalamina , Micelas , Nitrorredutases , Polímeros , Pró-Fármacos , Animais , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Mesalamina/química , Mesalamina/farmacocinética , Nitrorredutases/metabolismo , Camundongos , Colo/metabolismo , Colo/patologia , Polímeros/química , Colite/tratamento farmacológico , Colite/metabolismo , Preparações de Ação Retardada/química , NADH NADPH Oxirredutases/metabolismo , Camundongos Endogâmicos C57BL , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Masculino
7.
BMC Anesthesiol ; 24(1): 185, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789968

RESUMO

BACKGROUND: Despite the implementation of various postoperative management strategies, the prevalence of postoperative fatigue syndrome (POFS) remains considerable among individuals undergoing laparoscopic radical gastrectomy. While the N-methyl-D-aspartic acid receptor antagonist esketamine has demonstrated efficacy in enhancing sleep quality and alleviating postoperative pain, its impact on POFS remains uncertain. Consequently, the objective of this study is to ascertain whether perioperative administration of esketamine can effectively mitigate the occurrence of POFS in patients undergoing laparoscopic radical gastrectomy. METHODS: A total of 133 patients diagnosed with gastric cancer were randomly assigned to two groups, namely the control group (Group C) (n = 66) and the esketamine group (Group E) (n = 67), using a double-blind method. The Group C received standardized anesthesia, while the Group E received esketamine in addition to the standardized anesthesia. The primary outcome measure assessed was the Christensen fatigue score at 3 days after the surgical procedure, while the secondary outcomes included the disparities in postoperative fatigue, postoperative pain, sleep quality, and adverse reactions between the two groups. RESULTS: In the group receiving esketamine, the fatigue scores of Christensen on the third day after surgery were significantly lower compared to the Group C (estimated difference, -0.70; 95% CI, -1.37 to -0.03; P = 0.040). Additionally, there was a significant decrease in the occurrence of fatigue in the Group E compared to the Group C on the first and third days following surgery (P < 0.05). Also, compared to individuals who had distal gastrectomy, those who had entire gastrectomy demonstrated a higher degree of postoperative tiredness reduction with esketamine. Furthermore, the Group E exhibited reduced postoperative pain and improved sleep in comparison to the Group C. Both groups experienced similar rates of adverse events. CONCLUSIONS: The use of esketamine during the perioperative period can improve POFS after laparoscopic radical gastrectomy, without adverse reactions. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry (ChiCTR2300072167) on 05/06 /2023.


Assuntos
Gastrectomia , Ketamina , Laparoscopia , Dor Pós-Operatória , Complicações Pós-Operatórias , Neoplasias Gástricas , Humanos , Ketamina/administração & dosagem , Ketamina/uso terapêutico , Neoplasias Gástricas/cirurgia , Masculino , Feminino , Método Duplo-Cego , Laparoscopia/métodos , Pessoa de Meia-Idade , Gastrectomia/métodos , Complicações Pós-Operatórias/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Fadiga/prevenção & controle , Idoso
8.
Mar Drugs ; 22(2)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38393040

RESUMO

In this study, an actinomycete was isolated from sea mud. The strain K1 was identified as Saccharomonospora sp. by 16S rDNA. The optimal enzyme production temperature, initial pH, time, and concentration of the inducer of this actinomycete strain K1 were 37 °C, pH 8.5, 72 h, and 2% dextran T20 of medium, respectively. Dextranase from strain K1 exhibited maximum activity at 8.5 pH and 50 °C. The molecular weight of the enzyme was <10 kDa. The metal ions Sr2+ and K+ enhanced its activity, whereas Fe3+ and Co2+ had an opposite effect. In addition, high-performance liquid chromatography showed that dextran was mainly hydrolyzed to isomaltoheptose and isomaltopentaose. Also, it could effectively remove biofilms of Streptococcus mutans. Furthermore, it could be used to prepare porous sweet potato starch. This is the first time a dextranase-producing actinomycete strain was screened from marine samples.


Assuntos
Actinobacteria , Dextranos , Dextranos/química , Dextranase/química , Concentração de Íons de Hidrogênio , Biofilmes
9.
Yi Chuan ; 46(4): 279-289, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38632091

RESUMO

H2A.Z, one of the most well-known variants of histone H2A, has been extensively investigated on its dual roles in gene transcription in recent years. In this review, we focus on the intricate involvement of H2A.Z in transcriptional regulation, including the assembly of distinct H2A.Z subtypes, post-translational modifications and genomic distributions. Emphasis is placed on the biological and pathophysiological implications, particularly in tumorigenesis and nervous system development. We summarize the dynamic regulatory mechanisms governing H2A.Z deposition or eviction on chromatin to provide insights for understanding the diversity of histone variants and promoting the search of new targets in concerned disease diagnosis and treatment.


Assuntos
Histonas , Nucleossomos , Histonas/metabolismo , Cromatina , Regulação da Expressão Gênica , Genoma
10.
Zhongguo Zhong Yao Za Zhi ; 49(1): 130-140, 2024 Jan.
Artigo em Zh | MEDLINE | ID: mdl-38403346

RESUMO

This study induced biological stress in Sorbus pohuashanensis suspension cell(SPSC) with yeast extract(YE) as a bio-tic elicitor and isolated and identified secondary metabolites of triterpenoids produced under stress conditions. Twenty-six triterpenoids, including fifteen ursane-type triterpenoids(1-15), two 18,19-seco-ursane-type triterpenoids(16-17), four lupine-type triterpenoids(18-21), two cycloartane-type triterpenoids(22-23), and three squalene-type triterpenoids(24-26), were isolated and purified from the methanol extract of SPSC by chromatography on silica gel, MCI, Sephadex LH-20, and MPLC. Their structures were elucidated by spectroscopic analyses. All triterpenoids were isolated from SPSC for the first time and 22-O-acetyltripterygic acid A(1) was identified as a new compound. Selected compounds were evaluated for antifungal, antitumor, and anti-inflammatory activities, and compound 1 showed an inhibitory effect on NO production in LPS-induced RAW264.7 cells.


Assuntos
Triterpenos Pentacíclicos , Sorbus , Triterpenos , Animais , Camundongos , Sorbus/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Células RAW 264.7 , Estrutura Molecular
12.
Sci Total Environ ; 927: 171875, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38522530

RESUMO

Evaporative emission is an important source of vehicle pollutant emission and volatile organic compounds (VOCs), causing serious environmental pollution. Carbon canisters are used to store fuel vapor in evaporative emission control (EVAP) system, but canisters are prone to saturation, leading to the direct release of fuel vapor into the atmosphere. Therefore, accurate estimation of fuel vapor generation is crucial for EVAP system. Gasoline evaporation rate is mainly influenced by vapor-liquid interface area, gasoline saturated vapor pressure, filling level and temperature. The quantitative relation between different parameters and gasoline evaporation rate has rarely been reported, and a gasoline evaporative emission estimation model suitable for China needs to be proposed urgently. In this study, gasoline evaporative emission tests have been carried out in VT-SHED, and the effects of vapor-liquid interface area, filling level and temperature on gasoline evaporative emissions have been analyzed under the premise of consistent gasoline temperature and ambient temperature. Some valuable conclusions are obtained. The results show that different from expectation, gasoline evaporative emissions are not positively correlated with the vapor-liquid interface area. There is an approximately exponential relationship between the headspace volume and gasoline evaporative emissions. The widely used Reddy equation and Hata equation underestimate the gasoline vapor generation in China. Based on China VI test program and gasoline, accurate estimation of mass transfer coefficient has been conducted, and a new semi-empirical estimation model for vapor generation has been proposed. The model can accurately estimate the fuel evaporation of vehicles in China, providing guidance for the matching and optimization of EVAP system.

13.
Genes (Basel) ; 15(5)2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38790252

RESUMO

Genetic variation facilitates the evolution, environmental adaptability, and biodiversity of organisms. Danish Large White (LW) pigs have more desirable phenotypes compared with local Chinese pigs, which have difficulty adapting to the modern swine industry. However, the genome-wide mutational differences between these pig breeds are yet to be evaluated. Therefore, this study aimed to evaluate genomic variation and identify breed-specific SNPs in Danish LW pigs. Here, 43 LW, 15 Diqing Tibetan (DQZ), and 15 Diannan small-ear (DN) pigs whose genomes were re-sequenced with 5× depth were selected. This was followed by a conjoined analysis of our previous resequencing data of 24 Anqing six-end white (AQ) and six Asian wild (SS) pigs. In total, 39,158,378 SNPs and 13,143,989 insertion-deletions were obtained in all breeds. The variation number of LW pigs was the lowest, with 287,194 breed-specific and 1289 non-synonymous SNPs compared with Chinese breeds. Functional analysis of the breed-specific non-synonymous SNPs indicated that these mutations were mainly associated with the reproductive performance, feed intake, and feed conversion ratio of LW pigs. These findings provide a theoretical basis for genetic improvements in the Chinese swine industry.


Assuntos
Genoma , Polimorfismo de Nucleotídeo Único , Animais , Suínos/genética , Genoma/genética , Cruzamento , China , Sus scrofa/genética , Fenótipo
14.
Front Genet ; 15: 1381917, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38746057

RESUMO

MicroRNAs (miRNAs) are promising biomarkers for the early detection of disease, and many miRNA-based diagnostic models have been constructed to distinguish patients and healthy individuals. To thoroughly utilize the miRNA-profiling data across different sequencing platforms or multiple centers, the models accounting the batch effects were demanded for the generalization of medical application. We conducted transcription factor (TF)-mediated miRNA-miRNA interaction network analysis and adopted the within-sample expression ratios of miRNA pairs as predictive markers. The ratio of the expression values between each miRNA pair turned out to be stable across multiple data sources. A genetic algorithm-based classifier was constructed to quantify risk scores of the probability of disease and discriminate disease states from normal states in discovery, with a validation dataset for COVID-19, renal cell carcinoma, and lung adenocarcinoma. The predictive models based on the expression ratio of interacting miRNA pairs demonstrated good performances in the discovery and validation datasets, and the classifier may be used accurately for the early detection of disease.

15.
iScience ; 27(6): 110064, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38947514

RESUMO

Glioblastoma multiforme (GBM) is one of the most lethal brain tumors, characterized by profound heterogeneity. While single-cell transcriptomic studies have revealed extensive intra-tumor heterogeneity, shed light on intra-tumor diversity, spatial intricacies remain largely unexplored. Leveraging clinical GBM specimens, this study employs spatial transcriptomics technology to delve into gene expression heterogeneity. Our investigation unveils a significant enrichment of tissue stem cell signature in regions bordering necrosis and the peritumoral area, positively correlated with the mesenchymal subtype signature. Moreover, upregulated genes in these regions are linked with extracellular matrix (ECM)-receptor interaction, proteoglycans, as well as vascular endothelial growth factor (VEGF) and angiopoietin-Tie (ANGPT) signaling pathways. In contrast, signatures related to glycogen metabolism and oxidative phosphorylation show no relevance to pathological zoning, whereas creatine metabolism signature is notably exclusive to vascular-enriched areas. These spatial profiles not only offer valuable references but also pave the way for future in-depth functional and mechanistic investigations into GBM progression.

16.
Sci Bull (Beijing) ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-39030103

RESUMO

Exploiting the intelligent photocatalysts capable of phase separation provides a promising solution to the removal of uranium, which is expected to solve the difficulty in separation and the poor selectivity of traditional photocatalysts in carbonate-containing uranium wastewater. In this paper, the γ-FeOOH/konjac glucomannan grafted with phenolic hydroxyl groups/poly-N-isopropylacrylamide (γ-FeOOH/KGM(Ga)/PNIPAM) thermosensitive hydrogel is proposed as the photocatalysts for extracting uranium from carbonate-containing uranium wastewater. The dynamic phase transformation is demonstrated to confirm the arbitrary transition of γ-FeOOH/KGM(Ga)/PNIPAM thermosensitive hydrogel from a dispersed state with a high specific surface area at low temperatures to a stable aggregated state at high temperatures. Notably, the γ-FeOOH/KGM(Ga)/PNIPAM thermosensitive hydrogel achieves a remarkably high rate of 92.3% in the removal of uranium from the wastewater containing carbonates and maintains the efficiency of uranium removal from uranium mine wastewater at over 90%. Relying on electron spin resonance and free radical capture experiment, we reveal the adsorption-reduction-nucleation-crystallization mechanism of uranium on γ-FeOOH/KGM(Ga)/PNIPAM thermosensitive hydrogel. Overall, this strategy provides a promising solution to treating uranium-contaminated wastewater, showing a massive potential in water purification.

17.
Cell Rep ; 43(7): 114423, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38968072

RESUMO

Actin assembly and dynamics are crucial for maintaining cell structure and changing physiological states. The broad impact of actin on various cellular processes makes it challenging to dissect the specific role of actin regulatory proteins. Using actin waves that propagate on the cortex of mast cells as a model, we discovered that formins (FMNL1 and mDia3) are recruited before the Arp2/3 complex in actin waves. GTPase Cdc42 interactions drive FMNL1 oscillations, with active Cdc42 and the constitutively active mutant of FMNL1 capable of forming waves on the plasma membrane independently of actin waves. Additionally, the delayed recruitment of Arp2/3 antagonizes FMNL1 and active Cdc42. This antagonism is not due to competition for monomeric actin but rather for their common upstream regulator, active Cdc42, whose levels are negatively regulated by Arp2/3 via SHIP1 recruitment. Collectively, our study highlights the complex feedback loops in the dynamic control of the actin cytoskeletal network.


Assuntos
Complexo 2-3 de Proteínas Relacionadas à Actina , Actinas , Forminas , Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Actinas/metabolismo , Animais , Forminas/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo , Humanos , Mastócitos/metabolismo , Camundongos , Citoesqueleto de Actina/metabolismo
18.
Cell Signal ; 117: 111094, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38341123

RESUMO

Hypoxia-inducible transcription factors (HIFs) are key transcription factors for cellular response to low oxygen levels. However, the specific mediators responsible for activating downstream transcription are not well characterized. We previously identified Protein Arginine methyltransferase 2 (PRMT2), a highly expressed methyltransferase in glioblastoma multiforme, as a transcription co-activator. And we established a connection between PRMT2-mediated histone H3R8 asymmetric methylation (H3R8me2a) and transcription activation. Here we find that PRMT2 is activated by HIF1α under hypoxic conditions. And we demonstrate that PRMT2 and its H3R8me2a activity are required for the transcription activation of a significant subset of hypoxia-induced genes. Consequently, the inactivation of PRMT2 suppresses hypoxia-induced glioblastoma cell migration, attenuates tumor progression, and enhances chemotherapeutic sensitivity in mouse xenograft models. In addition, our analysis of clinical glioma specimens reveals a correlation between PRMT2 protein levels, HIF1α abundance, and an unfavorable prognosis. Our study establishes HIF1α-induced PRMT2 as a critical modulator in the activation of hypoxia-related transcriptional programs, ultimately driving malignant progression.


Assuntos
Glioblastoma , Humanos , Camundongos , Animais , Glioblastoma/genética , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Fatores de Transcrição/metabolismo , Metilação , Ativação Transcricional , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
19.
Int J Oral Sci ; 16(1): 38, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734708

RESUMO

Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm. The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress. Sinensetin (Sin) is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities. Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms. We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells (PDLCs) under inflammatory conditions. Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo. By molecular docking, we identified Bach1 as a strong binding target of Sin, and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays. Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter, subsequently upregulating the expression of the key antioxidant factor HO-1. Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects. Additionally, we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1, thereby inducing HO-1 expression and inhibiting oxidative stress. Overall, Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica , Flavonoides , Estresse Oxidativo , Periodontite , Ubiquitinação , Animais , Humanos , Masculino , Ratos , Antioxidantes/farmacologia , Fatores de Transcrição de Zíper de Leucina Básica/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Western Blotting , Imunoprecipitação da Cromatina , Modelos Animais de Doenças , Simulação de Acoplamento Molecular , Estresse Oxidativo/efeitos dos fármacos , Ligamento Periodontal/efeitos dos fármacos , Ligamento Periodontal/metabolismo , Ligamento Periodontal/citologia , Periodontite/tratamento farmacológico , Periodontite/prevenção & controle , Periodontite/metabolismo , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Ubiquitinação/efeitos dos fármacos , Flavonoides/farmacologia
20.
Chemosphere ; 361: 142544, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38844100

RESUMO

Nuclear energy is playing an increasingly important role on the earth, but the nuclear plants leaves a legacy of radioactive waste pollution, especially uranium-containing pollution. Straw biochar with wide sources, large output, low cost, and easy availability, has emerged as a promising material for uranium extraction from radioactive wastewater, but the natural biomass with suboptimal structure and low content of functional groups limits the efficiency. In this work, microbial etch was first came up to regulate the biochar's structure and function. The surface of the biochar becomes rougher and more microporous, and the mineral contents (Ca, P) indirectly increased by microbial etch. The biochar was modified by calcium phosphate and exhibited a remarkable uranium extraction capacity of 590.8 mg g-1 (fitted value). This work provides a cost-effective and sustainable method for preparing functionalized biochar via microbial etch, which has potential for application to uranium extraction from radioactive wastewater.


Assuntos
Carvão Vegetal , Urânio , Águas Residuárias , Carvão Vegetal/química , Urânio/química , Águas Residuárias/química , Resíduos Radioativos/análise , Poluentes Radioativos da Água , Fosfatos de Cálcio/química
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