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1.
Heliyon ; 10(9): e30244, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38720706

RESUMEN

Purpose: The integrator subunit (INTS) family, a group exclusive to metazoans, participates in various biologic processes. However, their roles in hepatocellular carcinoma (HCC) remain largely unexplored. Methods: Public databases were utilized to investigate the transcriptional and protein expression, and clinical relevance of the INTS family in HCC. Meanwhile, the effects of INTS13 knockdown and overexpression on cell proliferation and apoptosis were studied using HCC cell lines. Results: The mRNA expression of most INTSs were higher in tumor than normal tissues. Higher expression of INTS1/2/3/4/7/8/9/11/12/13 were correlated with poorer overall survival (OS) in Kaplan-Meier Survival Analysis. Multivariate analysis revealed higher level of INTS13 was an independent prognostic factor for shorter OS. Furthermore, genetic alteration of INTS3/6/7/8/9/10 were found in HCC patients and was associated with shorter disease-free survival and progression-free survival. INTS1/2/3/5/7/11/13/14 were associated with activation of tumor-induced immune response and immune infiltration in HCC. Knockdown of INTS13 inhibited cell proliferation and induced apoptosis in HCC cell lines, while overexpression of INTS13 had the opposite effect. Conclusion: Our results indicate that INTS13 is an independent prognostic biomarker in HCC. Furthermore, INTS13 enhances cell proliferation and decreases cell apoptosis in HCC cell lines leading to a poorer OS in HCC patients.

2.
Heliyon ; 10(9): e29860, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38707433

RESUMEN

Background: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent liver disease worldwide and lack of research on the diagnostic utility of mitochondrial regulators in NAFLD. Mitochondrial dysfunction plays a pivotal role in the development and progression of NAFLD, especially oxidative stress and acidity ß-oxidative overload. Thus, we aimed to identify and validate a panel of mitochondrial gene expression biomarkers for detection of NAFLD. Methods: We selected the GSE89632 dataset and identified key mitochondrial regulators by intersecting DEGs, WGCNA modules, and MRGs. Classification of NAFLD subtypes based on these key mitochondrial regulatory factors was performed, and the pattern of immune system infiltration in different NAFLD subtypes were also investigated. RF, LASSO, and SVM-RFE were employed to identify possible diagnostic biomarkers from key mitochondrial regulatory factors and the predictive power was demonstrated through ROC curves. Finally, we validated these potential diagnostic biomarkers in human peripheral blood samples and a high-fat diet-induced NAFLD mouse model. Results: We identified 25 key regulators of mitochondria and two NAFLD subtypes with different immune infiltration patterns. Four potential diagnostic biomarkers (BCL2L11, NAGS, HDHD3, and RMND1) were screened by three machine learning methods thereby establishing the diagnostic model, which showed favorable predictive power and achieved significant clinical benefit at certain threshold probabilities. Then, through internal and external validation, we identified and confirmed that BCL2L11 was significantly downregulated in NAFLD, while the other three were significantly upregulated. Conclusion: The four MRGs, namely BCL2L11, NAGS, HDHD3, and RMND1, are novel potential biomarkers for diagnosing NAFLD. A diagnostic model constructed using the four MRGs may aid early diagnosis of NAFLD in clinics.

3.
Arch Biochem Biophys ; 755: 109983, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38561035

RESUMEN

Apelin (APLN) is an endogenous ligand of the G protein-coupled receptor APJ (APLNR). APLN has been implicated in the development of multiple tumours. Herein, we determined the effect of APLN on the biological behaviour and underlying mechanisms of cervical cancer. The expression and survival curves of APLN were determined using Gene Expression Profiling Interactive Analysis. The cellular functions of APLN were detected using CCK-8, clone formation, EdU, Transwell assays, flow cytometry, and seahorse metabolic analysis. The underlying mechanisms were elucidated using gene set enrichment analysis and Western blotting. APLN was upregulated in the samples of patients with cervical cancer and is associated with poor prognosis. APLN knockdown decreased the proliferation, migration, and glycolysis of cervical cancer cells. The opposite results were observed when APLN was overexpressed. Mechanistically, we determined that APLN was critical for activating the PI3K/AKT/mTOR pathway via APLNR. APLN receptor inhibitor ML221 reversed the effect of APLN overexpression on cervical cancer cells. Treatment with LY294002, the PI3K inhibitor, drastically reversed the oncological behaviour of APLN-overexpressing C-33A cells. APLN promoted the proliferation, migration, and glycolysis of cervical cancer cells via the PI3K/AKT/mTOR pathway.

4.
J Drug Target ; : 1-8, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38682473

RESUMEN

Liver fibrosis is a common pathological condition marked by excessive accumulation of extracellular matrix proteins, resulting in irreversible cirrhosis and cancer. Dendritic cells (DCs) act as the crucial component of hepatic immunity and are believed to affect fibrosis by regulating the proliferation and differentiation of hepatic stellate cells (HSCs), a key mediator of fibrogenesis, and by interplaying with immune cells in the liver. This review concisely describes the process of fibrogenesis, and the phenotypic and functional characteristics of DCs in the liver. Besides, it focuses on the interaction between DCs and HSCs, T cells, and natural killer (NK) cells, as well as the dual roles of DCs in liver fibrosis, for the sake of exploring the potential of targeting DCs as a therapeutic strategy for the disease.

5.
Chin J Traumatol ; 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38490942

RESUMEN

PURPOSE: The current study aimed to assess the protective performance of helmets equipped with a multi-directional impact protection system (MIPS) under various oblique impact loads. METHODS: Initially, a finite element model of a bicycle helmet with MIPS was developed based on the scanned geometric parameters of an actual bicycle helmet. Subsequently, the validity of model was confirmed using the KASK WG11 oblique impact test method. Three different impact angles (30°, 45°, and 60°) and 2 varying impact speeds (5 m/s and 8 m/s) were employed in oblique tests to evaluate protective performance of MIPS in helmets, focusing on injury assessment parameters such as peak linear acceleration (PLA) and peak angular acceleration (PAA) of the head. RESULTS: The results demonstrated that in all impact simulations, both assessment parameters were lower during impact for helmets equipped with MIPS compared to those without. The PAA was consistently lower in the MIPS helmet group, whereas the difference in resulting PLA was not significant in the no-MIPS helmet group. For instance, at an impact velocity of 8 m/s and a 30° inclined anvil, the MIPS helmet group exhibited a PAA of 3225 rad/s2 and a PLA of 281 g. In contrast, the no-MIPS helmet group displayed a PAA of 8243 rad/s2 and a PLA of 292 g. Generally, both PAA and PLA parameters decreased with increasing anvil angle. At a 60° anvil angle, PAA and PLA values were 664 rad/s2 and 20.7 g, respectively, reaching their minimum. CONCLUSION: The findings indicated that helmets incorporating MIPS offer enhanced protection against various oblique impact loads. When assessing helmets for oblique impacts, the utilization of larger angle anvils and rear impacts might not adequately evaluate protective performance during an impact event. These findings will guide advancements in helmet design and the refinement of oblique impact test protocols.

6.
J Hazard Mater ; 469: 133946, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38442603

RESUMEN

Hydrothermal carbonization process water (HTPW) has been utilized as a substitute for chemical fertilizers in agricultural applications. However, the input of HTPW into paddy water, particularly the significant proportion of dissolved organic matter (DOM) in HTPW (DOM-HTPW), directly engages in photochemical transformations, a phenomenon often overlooked. This study observed a consistent decrease in humification (SUVA280, 7.7-53.9%) and aromaticity (SUVA254, 6.1-40.0%) of DOM-HTPW after irradiation. The primary active photobleaching components of DOM-HTPW varied depending on the feedstock, such as protein for chicken manure DOM-HTPW and lignin for rice straw DOM-HTPW. The photochemical activity of DOM-HTPW was augmented by its lower molecular weight and higher hydrophilic composition, particularly evident in chicken manure DOM-HTPW, which exhibited higher generation rates for 1O2 (35.1-37.1%), 3DOM* (32.8-43.9%), and O2•- (28.6-48.8%) as measured by molecular probes. DOM-HTPW effectively facilitated the phototransformation of tetracycline, with the contribution of O2•- being more significant than 3DOM* and 1O2. These findings shed new light on the understanding the photochemical processes of DOM-HTPW as exogenous DOM and the interconnected fate of contaminants in aquatic environments.

7.
Biomed Pharmacother ; 172: 116317, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38382329

RESUMEN

Gastric cancer (GC) is difficult to characterize due to its heterogeneity, and the complicated heterogeneity leads to the difficulty of precisely targeted therapy. The spatially heterogeneous composition plays a crucial role in GC onset, progression, treatment efficacy, and drug resistance. In recent years, the technological advancements in spatial omics has shifted our understanding of the tumor microenvironment (TME) from cancer-centered model to a dynamic and variant whole. In this review, we concentrated on the spatial heterogeneity within the primary lesions and between the primary and metastatic lesions of GC through the TME heterogeneity including the tertiary lymphoid structures (TLSs), the uniquely spatial organization. Meanwhile, the immune phenotype based on spatial distribution was also outlined. Furthermore, we recapitulated the clinical treatment in mediating spatial heterogeneity in GC, hoping to provide a systematic view of how spatial information could be integrated into anti-cancer immunity.


Asunto(s)
Neoplasias Gástricas , Estructuras Linfoides Terciarias , Humanos , Microambiente Tumoral , Neoplasias Gástricas/genética , Fenotipo
8.
Glob Heart ; 19(1): 19, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38371655

RESUMEN

Background: Depression has a significant effect on cardiovascular disease (CVD), but uncertainties persist regarding which modifiable risk factors mediate the causal effects. We aim to determine whether depression is causally linked to CVD and which modifiable risk factors play potential mediating roles. Methods: We used a two-sample Mendelian randomization (MR) approach and NHANES 2007-2018 data to estimate the effects of depression on various CVD cases and investigated 28 potential mediators of the association between depression and CVD. Results: The results of our MR analysis indicated that genetically determined depression was associated with increased risk of several CVD, including coronary heart disease (odds ratio (OR) = 1.14; 95% confidence interval (CI): 1.05,1.22), myocardial infarction (OR = 1.19; 95% CI, 1.09,1.31), atrial fibrillation (OR = 1.14; 95% CI, 1.06,1.22), and stroke (OR = 1.13; 95% CI, 1.05,1.22). However, there was no causal association between depression and heart failure. Four out of 28 cardiometabolic risk factors, including hyperlipidemia, hypertension, diabetes, and prescription opioid use, were identified as mediators of the association between depression and various CVDs. Observational association analyses from NHANES data yielded consistent results. Conclusion: Our findings demonstrated that depression has a causal detrimental effect on various CVDs. Four causal mediators (hyperlipidemia, hypertension, diabetes, and prescription opioid use) were screened to explain the causal effect. Implementing targeted management strategies for these risk factors may be warranted to mitigate the public health burden of CVD among individuals with depression.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus , Hiperlipidemias , Hipertensión , Infarto del Miocardio , Humanos , Analgésicos Opioides , Análisis de la Aleatorización Mendeliana , Encuestas Nutricionales , Infarto del Miocardio/epidemiología , Infarto del Miocardio/genética , Polimorfismo de Nucleótido Simple
9.
Environ Sci Technol ; 58(6): 3019-3030, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38308619

RESUMEN

Hydrochar, recognized as a green and sustainable soil amendment, has garnered significant attention. However, information on the aging process in soil and the temporal variability of hydrochar remains limited. This study delves deeper into the interaction between hydrochar and soil, focusing on primary factors influencing hydrochar aging during a 30-month rice-wheat rotation system. The results showed that the initial aging of hydrochar (0-16 months) is accompanied by the development of specific surface area and leaching of hydrochar-derived dissolved organic matter (HDOM), resulting in a smaller particle size and reduced carbon content. The initial aging also features a mineral shield, while the later aging (16 to 30 months) involves surface oxidation. These processes collectively alter the surface charge, hydrophilicity, and composition of aged hydrochar. Furthermore, this study reveals a dynamic interaction between the HDOM and DOM derived from soil, plants, and microbes at different aging stages. Initially, there is a preference for decomposing labile carbon, whereas later stages involve the formation of components with higher aromaticity and molecular weight. These insights are crucial for understanding the soil aging effects on hydrochar and HDOM as well as evaluating the interfacial behavior of hydrochar as a sustainable soil amendment.


Asunto(s)
Materia Orgánica Disuelta , Oryza , Triticum , Suelo , Carbono
10.
Biol Reprod ; 110(4): 739-749, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38206868

RESUMEN

The occurrence of unexplained recurrent spontaneous abortion (URSA) is closely related to immune system disorders, however, the underlying mechanisms remain unclear. The purpose of this study was to investigate the expression of GRIM-19 in URSA and the possible pathogenesis of URSA according to macrophage polarization. Here, we showed that GRIM-19 was downregulated in the uterine decidual macrophages of patients with URSA and that GRIM-19 downregulation was accompanied by increased M1 macrophage polarization. Furthermore, the expression levels of glycolytic enzymes were substantially enhanced in the uterine decidual macrophages of URSA patients, and glycolysis in THP-1-derived macrophages was further enhanced by the downregulation of GRIM-19. Additionally, the increase of M1 macrophages resulting from the loss of GRIM-19 was significantly reversed in cells treated with 2-deoxy-D-glucose (2-DG, an inhibitor of glycolysis). To provide more direct evidence, GRIM-19 deficiency was shown to promote macrophage polarization to the M1 phenotype in GRIM-19+/- mouse uteri. Overall, our study provides evidence that GRIM-19 deficiency may play a role in regulating macrophage polarization in URSA, and that glycolysis may participate in this process.


Asunto(s)
Aborto Habitual , Aborto Espontáneo , Macrófagos , NADH NADPH Oxidorreductasas , Animales , Femenino , Humanos , Ratones , Embarazo , Aborto Habitual/genética , Aborto Espontáneo/genética , Macrófagos/metabolismo , Fenotipo , Glucólisis , NADH NADPH Oxidorreductasas/genética , NADH NADPH Oxidorreductasas/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo
11.
Sci Total Environ ; 917: 170419, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38296091

RESUMEN

The rare earth metal element lanthanum (La) possesses carcinogenic, genotoxic, and accumulative properties, necessitating urgent development of an efficient and cost-effective method to remove La. However, current sorbents still encounter challenges such as poor selectivity, low sorption capacity, and high production costs. This study therefore proposes a promising solution: the creation of phytic acid-assisted sludge hydrochars (P-SHCs) to eliminate La from water and soil environments. This method harnesses phytic acid's exceptional binding ability and the economical hydrothermal carbonization process. P-SHCs exhibit robust sorption affinity, fast sorption kinetics, and excellent sorption selectivity for La when compared with pristine hydrochars (SHCs). This advantage arises from the remarkable binding ability of phosphate functional groups (polyphosphates) on P-SHCs, forming P-O-La complexes. Moreover, P-SHCs demonstrate sustained sorption efficiency across at least five cycles, with a slight decrease attributed to the loss of phosphorus species and mass during recycling. Furthermore, P-SHCs demonstrated superior economic feasibility, with a higher estimated cost-benefit ratio than that of other sorbents. Our study further validates the exceptional passivation capability of P-SHCs, showcasing relative stabilization efficiency ranging from 37.6 % to 79.6 % for La contamination. Additionally, acting as soil passivation agents, P-SHCs foster the enrichment of specific soil microorganisms such as Actinobacteria and Proteobacteria, capable of solubilizing phosphorus and resisting heavy metals. These findings present novel ideas and technical support for employing P-SHCs in combatting environmental pollution stemming from rare earth metals.


Asunto(s)
Lantano , Ácido Fítico , Lantano/química , Fósforo , Suelo , Polifosfatos , Adsorción
12.
J Immunol ; 212(4): 723-736, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38197667

RESUMEN

N 6-methyladenosine (m6A) is the most abundant mRNA modification in mammals and it plays a vital role in various biological processes. However, the roles of m6A on cervical cancer tumorigenesis, especially macrophages infiltrated in the tumor microenvironment of cervical cancer, are still unclear. We analyzed the abnormal m6A methylation in cervical cancer, using CaSki and THP-1 cell lines, that might influence macrophage polarization and/or function in the tumor microenvironment. In addition, C57BL/6J and BALB/c nude mice were used for validation in vivo. In this study, m6A methylated RNA immunoprecipitation sequencing analysis revealed the m6A profiles in cervical cancer. Then, we discovered that the high expression of METTL14 (methyltransferase 14, N6-adenosine-methyltransferase subunit) in cervical cancer tissues can promote the proportion of programmed cell death protein 1 (PD-1)-positive tumor-associated macrophages, which have an obstacle to devour tumor cells. Functionally, changes of METTL14 in cervical cancer inhibit the recognition and phagocytosis of macrophages to tumor cells. Mechanistically, the abnormality of METTL14 could target the glycolysis of tumors in vivo and vitro. Moreover, lactate acid produced by tumor glycolysis has an important role in the PD-1 expression of tumor-associated macrophages as a proinflammatory and immunosuppressive mediator. In this study, we revealed the effect of glycolysis regulated by METTL14 on the expression of PD-1 and phagocytosis of macrophages, which showed that METTL14 was a potential therapeutic target for treating advanced human cancers.


Asunto(s)
Metiltransferasas , Neoplasias del Cuello Uterino , Animales , Femenino , Humanos , Ratones , Adenosina/análogos & derivados , Glucólisis , Macrófagos , Mamíferos , Metiltransferasas/metabolismo , Ratones Endogámicos C57BL , Ratones Desnudos , Fagocitosis , Fenotipo , Receptor de Muerte Celular Programada 1 , Microambiente Tumoral , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/enzimología , Neoplasias del Cuello Uterino/inmunología , Línea Celular Tumoral
13.
Environ Res ; 243: 117853, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38070856

RESUMEN

Biochar-based organic fertilizer is a new type of ecological fertilizer formulated with organic fertilizers using biochar as the primary conditioning agent, which has received wide attention and application in recent years. This study conducted a comprehensive bibliometric analysis of the main hot spots and research trends in the field of biochar-based organic fertilizer research by collecting indicators (publication year, number, prominent authors, and research institutions) in the Web of Science database. The results showed that the research in biochar-based organic fertilizer has been in a rapid development stage since 2015, with exponential growth in publications number; the main institution with the highest publications number was Northwest Agriculture & Forestry University; the researchers with the highest number of publications was Mukesh Kumar Awasthi; the most publications country is China by Dec 30, 2022. The hot spots of biochar-based organic fertilizer research have been nitrogen utilization, greenhouse gas emission, composting product quality and soil fertility. Biochar reduces ammonia volatilization and greenhouse gas emissions from compost mainly through adsorption. The results showed that adding 10% biochar was an effective measure to achieve co-emission reduction of ammonia and greenhouse gases in composting process. In addition, biochar modification or combination with other additives should be the focus of future research to mitigate ammonia and greenhouse gas emissions from composting processes.


Asunto(s)
Carbón Orgánico , Compostaje , Gases de Efecto Invernadero , Humanos , Gases de Efecto Invernadero/análisis , Amoníaco , Fertilizantes/análisis , Volatilización , Nitrógeno/análisis , Suelo , Agricultura , Óxido Nitroso
14.
J Hazard Mater ; 465: 133316, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38128227

RESUMEN

Graphene oxide (GO) is an oxidized form of graphene-based materials with abundant hydrophilic oxygen-containing functional groups, forming well-dispersed suspensions and serving as pollution carriers. The natural anaerobic environment might alter the sorption behavior of GO, which in turn affects the fate and bioavailability of GO-sorbed organic contaminants. In this study, GO can be reduced by diverse environmental reductants, including sodium sulfide, DL-1,4-dithiothretiol, and L-cysteine, forming aggregates. Meanwhile, the GO-sorbed organic contaminants were released during the reduction process owing to the decreasing oxygen content and sorption sites. The effect of solution chemistry conditions (dissolved humic acid/HA and ionic strength) on the reduction release process was also investigated. HA reduced the release rate of organic contaminants due to its stabilization effect. Adding NaCl did not alter the release rate, while CaCl2 markedly enhanced the release rate. Toxicity tests with Bacillus subtilis indicated that releasing the pre-sorbed organic compound on GO led to a lower survival ratio and enhanced the superoxide dismutase activity. The findings of this study imply that the anaerobic environment could alter the dispersion/aggregation status of GO, affecting the sorption interaction between GO and the organic compounds and consequently influencing the toxicity and risk of pollution in the environment.


Asunto(s)
Grafito , Grafito/química , Óxidos/química , Anaerobiosis , Oxígeno
15.
BMC Complement Med Ther ; 23(1): 453, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38093254

RESUMEN

BACKGROUND: Craniotomy aneurysm clipping is one of the main treatments for intracranial aneurysm (IA). Endotracheal intubation and intraoperative operation may induce dramatic hemodynamic fluctuations and increase the risk of aneurysm rupture. Intraoperative high-dose opioid use is the main measure to reduce the intraoperative stress response, but it increases the incidence of complications such as postoperative vomiting and delayed awakening. Transcutaneous electrical acupoint stimulation (TEAS) stimulates ß-endorphin expression levels and reduces opioid requirements. In this study, we aimed to assess the effects of TEAS on remifentanil dosage and oxidative stress (OS) in craniotomy aneurysm clipping. METHOD: Forty-two patients with craniotomy aneurysm clipping were randomized into two groups: the TEAS group (T group) and the sham TEAS group (S group). "Hegu" (LI4), "Neiguan" (PC6) and "Zusanli" points (ST36) were selected, and a "HANS" percutaneous acupoint electrical stimulator was used for intervention 30 min before anesthesia induction until the end of the operation. The primary outcome was intraoperative remifentanil dosage. The secondary outcomes were intraoperative propofol dosage, mean arterial pressure (MAP) and heart rate (HR) 5 min before the TEAS intervention (T0), 5 min before head holder pinning (T1), immediately after pinning (T2), 5 min before craniotomy (T3), immediately after craniotomy (T4), at craniotomy (T5), and at the end of surgery (T6), as well as serum ß-endorphin levels at T1, T2 and T6 and neuron-specific enolase (NSE), S100ß, superoxide dismutase (SOD) and malondialdehyde (MDA) levels at T1, T2 and 24 h after surgery (T7). RESULTS: The dosage of remifentanil in the T group was reduced compared to that in the S group (P < 0.05). At T2, T4 and T5, the MAP and HR in the T group were lower than those in the S group (P < 0.05). At T2 and T7, the levels of NSE, S100ß and MDA in group T were lower than those in group S (P < 0.05), while the SOD levels in group T were higher than those in group S (P < 0.05). CONCLUSIONS: The use of TEAS can reduce the dosage of remifentanil and reduce hemodynamic fluctuations during craniotomy aneurysm clipping. It reduces the occurrence of OS and central nervous system damage during surgery and has a certain brain protective effect. TRIAL REGISTRATION: ChiCTR2100052353. https://www.chictr.org.cn/about.html .


Asunto(s)
Aneurisma , Estimulación Eléctrica Transcutánea del Nervio , Humanos , Remifentanilo , Analgésicos Opioides , Puntos de Acupuntura , Estudios Prospectivos , betaendorfina , Craneotomía , Superóxido Dismutasa
16.
Cell Death Dis ; 14(11): 734, 2023 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-37951987

RESUMEN

Cervical cancer (CC) is a gynecological neoplasm with the highest incidence rate, primarily attributed to the persistent infection of high-risk Human papillomavirus (HPV). Despite extensive research, the pathogenesis of CC remains unclear. N6-methyladenosine (m6A) methylation, the most prevalent form of epigenetic modification in RNA, is intricately linked to cell proliferation, metastasis, metabolism, and therapeutic resistance within the tumor microenvironment (TME) of CC. The involvement of the writer, reader, and eraser in m6A modification impacts the advancement of tumors through the regulation of RNA stability, nuclear export, translation efficiency, and RNA degradation. Here, we discuss the biogenesis of m6A, the atypical expressions of m6A regulators, the mechanisms of molecular interactions, and their functions in CC. Furthermore, we elucidate m6A modification of non-coding RNA. In the context of precision medicine, and with the advancements of genomics, proteomics, and high-throughput sequencing technologies, we summarize the application of m6A in the clinical diagnosis and treatment of CC. Additionally, new perspectives on detection methods, immune regulation, and nano-drug development are presented, which lay the foundation for further research of m6A and provide new ideas for the clinical treatment of CC.


Asunto(s)
Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/genética , Metilación , ARN , Adenosina , Proliferación Celular , Microambiente Tumoral
17.
Front Pharmacol ; 14: 1228895, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37781698

RESUMEN

Ketamine is a racemic mixture of equal amounts of R-ketamine and S-ketamine and is well known to anesthesiologists for its unique dissociative anesthetic properties. The pharmacological properties of ketamine, namely, its sympathetic excitation, mild respiratory depression, and potent analgesia, are still highly valued in its use as an anesthetic for some patients. In particular, since its advent, S-ketamine has been widely used as an anesthetic in many countries due to its increased affinity for NMDA receptors and its enhanced anesthetic and analgesic effects. However, the anesthetic and analgesic mechanisms of S-ketamine are not fully understood. In addition to antagonizing NMDA receptors, a variety of other receptors or channels may be involved, but there are no relevant mechanistic summaries in the literature. Therefore, the purpose of this paper is to review the mechanisms of action of S-ketamine on relevant receptors and systems in the body that result in its pharmacological properties, such as anesthesia and analgesia, with the aim of providing a reference for its clinical applications and research.

18.
iScience ; 26(10): 108012, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37766972

RESUMEN

[This corrects the article DOI: 10.1016/j.isci.2023.107673.].

19.
iScience ; 26(9): 107673, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37705956

RESUMEN

Long noncoding RNA (lncRNA) plays crucial roles in the development of gastric cancer (GC); however, studies of their mechanisms of action are needed to determine their clinical value. The aim of this study is to explore the effects and mechanisms of THUMPD3-AS1 in GC. Elevated levels of THUMPD3-AS1 were observed in GC and demonstrated a significant positive correlation with poor prognosis. Functionally, THUMPD3-AS1 promoted GC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) and induced tumor growth in vivo. THUMPD3-AS1 exerts its regulatory function on BCAT1 through competitive binding with miR-1297. Further investigations confirmed that both THUMPD3-AS1 and miR-1297 interact with BCAT1. These findings suggest that THUMPD3-AS1 promotes GC invasion and EMT by regulating the miR-1297/BCAT1 pathway, indicating that THUMPD3-AS1 may serve as a biomarker and therapeutic target for GC.

20.
ACS Appl Mater Interfaces ; 15(36): 43193-43204, 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37668232

RESUMEN

Cyclodextrins have been frequently used to fabricate membranes via interfacial polymerization (IP). However, the relatively low reactivity of pristine cyclodextrins often induces a lower cross-linking density and unsatisfactory separation performance. In this work, to introduce a highly active thiolated ß-cyclodextrin (CD-SH) monomer into IP progress, we constructed a dense and porous poly(thioester) linkage on a commercial membrane surface with loose nanofiltration by IP of CD-SH and trimesoyl trichloride (TMC) as the monomer in an aqueous phase and organic phase separately for the first time. Furthermore, the reactivity of CD-SH has been fully demonstrated by the two-phase IP aiming at unmodified ß-CD, a CD-SH/TMC freestanding membrane with a thicker interfacial layer and a smoother surface, and a PAN/CD-SH membrane with a narrow porous distribution. The composite membrane possessed superior separation performance for a high rejection (83.1-99.6%) of different anionic dyes and a low rejection (<20%) of salts, as well as a high-efficiency sieving ability of dye/dye and dye/salt mixtures. The membrane with a poly(thioester) selective layer could steadily operate in a long-term filtration test and exhibit great stability, chloride-resistance performance, and recyclability.

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