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2.
Front Endocrinol (Lausanne) ; 15: 1332895, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38694937

RESUMEN

Background: More than 700 million people worldwide suffer from diseases of the pancreas, such as diabetes, pancreatitis and pancreatic cancer. Often dysregulation of potassium (K+) channels, co-transporters and pumps can promote development and progression of many types of these diseases. The role of K+ transport system in pancreatic cell homeostasis and disease development remains largely unexplored. Potassium isotope analysis (δ41K), however, might have the potential to detect minute changes in metabolic processes relevant for pancreatic diseases. Methods: We assessed urinary K isotope composition in a case-control study by measuring K concentrations and δ41K in spot urines collected from patients diagnosed with pancreatic cancer (n=18), other pancreas-related diseases (n=14) and compared those data to healthy controls (n=16). Results: Our results show that urinary K+ levels for patients with diseased pancreas (benign and pancreatic cancer) are significantly lower than the healthy controls. For δ41K, the values tend to be higher for individuals with pancreatic cancer (mean δ41K = -0.58 ± 0.33‰) than for healthy individuals (mean δ41K = -0.78 ± 0.19‰) but the difference is not significant (p=0.08). For diabetics, urinary K+ levels are significantly lower (p=0.03) and δ41K is significantly higher (p=0.009) than for the healthy controls. These results suggest that urinary K+ levels and K isotopes can help identify K disturbances related to diabetes, an associated factors of all-cause mortality for diabetics. Conclusion: Although the K isotope results should be considered exploratory and hypothesis-generating and future studies should focus on larger sample size and δ41K analysis of other K-disrupting diseases (e.g., chronic kidney disease), our data hold great promise for K isotopes as disease marker.


Asunto(s)
Diabetes Mellitus , Neoplasias Pancreáticas , Potasio , Humanos , Neoplasias Pancreáticas/orina , Masculino , Femenino , Estudios de Casos y Controles , Persona de Mediana Edad , Anciano , Potasio/orina , Diabetes Mellitus/orina , Diabetes Mellitus/metabolismo , Adulto , Páncreas/metabolismo , Isótopos/orina
3.
Small ; : e2310037, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38634208

RESUMEN

Highly concentrated "'water-in-salt"' (WIS) electrolytes are promising for high-performance energy storage devices due to their wide electrochemical stability window. However, the energy storage mechanism of MnO2 in WIS electrolytes-based supercapacitors remains unclear. Herein, MnO2 nanoflowers are successfully grown on mesoporous bowl-like carbon (MBC) particles to generate MnO2/MBC composites, which not only increase electroactive sites and inhibit the pulverization of MnO2 particles during the fast charging/discharging processes, but also facilitate the electron transfer and ion diffusion within the whole electrode, resulting in significant enhancement of the electrochemical performance. An asymmetric supercapacitor, assembled with MnO2/MBC and activated carbon (AC) and using 21 m LiTFSI solution as the WIS electrolyte, delivers an ultrahigh energy density of 70.2 Wh kg-1 at 700 W kg-1, and still retains 24.8 Wh kg-1 when the power density is increased to 28 kW kg-1. The ex situ XRD, Raman, and XPS measurements reveal that a reversible reaction of MnO2 + xLi+ + xe-↔LixMnO2 takes place during charging and discharging. Therefore, the asymmetric MnO2/MBC//AC supercapacitor with LiTFSI electrolyte is actually a lithium-ion hybrid supercapacitor, which can greatly boost the energy density of the assembled device and expand the voltage window.

4.
Materials (Basel) ; 17(8)2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38673146

RESUMEN

The development of a new generation of solid particle solar receivers (SPSRs) with high solar absorptivity (0.28-2.5 µm) and high infrared emissivity (1-22 µm) is crucial and has attracted much attention for the attainment of the goals of "peak carbon" and "carbon neutrality". To achieve the modulation of infrared emission and solar absorptivity, two types of medium- and high-entropy rare-earth hexaboride (ME/HEREB6) ceramics, (La0.25Sm0.25Ce0.25Eu0.25)B6 (MEREB6) and (La0.2Sm0.2Ce0.2Eu0.2Ba0.2)B6 (HEREB6), with severe lattice distortions were synthesized using a high-temperature solid-phase method. Compared to single-phase lanthanum hexaboride (LaB6), HEREB6 ceramics show an increase in solar absorptivity from 54.06% to 87.75% in the range of 0.28-2.5 µm and an increase in infrared emissivity from 76.19% to 89.96% in the 1-22 µm wavelength range. On the one hand, decreasing the free electron concentration and the plasma frequency reduces the reflection and ultimately increases the solar absorptivity. On the other hand, the lattice distortion induces changes in the B-B bond length, leading to significant changes in the Raman scattering spectrum, which affects the damping constant and ultimately increases the infrared emissivity. In conclusion, the multicomponent design can effectively improve the solar energy absorption and heat transfer capacity of ME/HEREB6, thus providing a new avenue for the development of solid particles.

5.
Medicina (Kaunas) ; 60(4)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38674191

RESUMEN

There is currently no consensus on the optimal placement of the tibial tunnel for double-bundle posterior cruciate ligament (PCL) reconstruction. The purpose of this study was to compare the clinical and radiologic outcomes of double-bundle PCL reconstruction utilizing anatomic versus low tibial tunnels. We conducted a retrospective cohort study involving patients who underwent double-bundle PCL reconstruction between Jan 2019 and Jan 2022, with a minimum follow-up of 2 years (n = 36). Based on the tibial tunnel position on postoperative computed tomography, patients were categorized into two groups: anatomic placement (group A; n = 18) and low tunnel placement (group L; n = 18). We compared the range of motion, stability test, complications, and side-to-side differences in tibial posterior translation using kneeling stress radiography between the two groups. There were no significant differences between the groups regarding clinical outcomes or complication rates. No significant differences in the posterior drawer test and side-to-side difference on kneeling stress radiography (2.5 ± 1.2 mm in group A vs. 3.7 ± 2.0 mm in group L; p = 0.346). In conclusion, the main findings of this study indicate that both anatomic tunnel and low tibial tunnel placements in double-bundle PCL reconstruction demonstrated comparable and satisfactory clinical and radiologic outcomes, with similar overall complication rates at the 2-year follow-up.


Asunto(s)
Reconstrucción del Ligamento Cruzado Posterior , Tibia , Humanos , Masculino , Femenino , Estudios Retrospectivos , Adulto , Tibia/cirugía , Tibia/diagnóstico por imagen , Estudios de Seguimiento , Reconstrucción del Ligamento Cruzado Posterior/métodos , Rango del Movimiento Articular , Persona de Mediana Edad , Resultado del Tratamiento , Ligamento Cruzado Posterior/cirugía , Ligamento Cruzado Posterior/lesiones , Tomografía Computarizada por Rayos X/métodos , Estudios de Cohortes , Radiografía/métodos
6.
World J Gastroenterol ; 30(8): 969-983, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38516239

RESUMEN

BACKGROUND: Three-dimensional organoid culture systems have been established as a robust tool for elucidating mechanisms and performing drug efficacy testing. The use of gastric organoid models holds significant promise for advancing personalized medicine research. However, a comprehensive bibliometric review of this bur-geoning field has not yet been published. AIM: To analyze and understand the development, impact, and direction of gastric organoid research using bibliometric methods using data from the Web of Science Core Collection (WoSCC) database. METHODS: This analysis encompassed literature pertaining to gastric organoids published between 2010 and 2023, as indexed in the WoSCC. CiteSpace and VOSviewer were used to depict network maps illustrating collaborations among authors, institutions and keywords related to gastric organoid. Citation, co-citation, and burst analysis methodologies were applied to assess the impact and progress of research. RESULTS: A total of 656 relevant studies were evaluated. The majority of research was published in gastroenterology-focused journals. Globally, Yana Zavros, Hans Clevers, James M Wells, Sina Bartfeld, and Chen Zheng were the 5 most productive authors, while Hans Clevers, Huch Meritxell, Johan H van Es, Marc Van de Wetering, and Sato Toshiro were the foremost influential scientists in this area. Institutions from the University Medical Center Utrecht, Netherlands Institute for Developmental Biology (Utrecht), and University of Cincinnati (Cincinnati, OH, United States) made the most significant contributions. Currently, gastric organoids are used mainly in studies investigating gastric cancer (GC), Helicobacter pylori-infective gastritis, with a focus on the mechanisms of GC, and drug screening tests. CONCLUSION: Key focus areas of research using gastric organoids include unraveling disease mechanisms and enhancing drug screening techniques. Major contributions from renowned academic institutions highlight this field's dynamic growth.


Asunto(s)
Gastritis , Infecciones Intraabdominales , Neoplasias Gástricas , Humanos , Centros Médicos Académicos , Bibliometría
7.
Sci Rep ; 14(1): 4728, 2024 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-38413668

RESUMEN

Tea is an indispensable beverage in people's daily life. However, the relationship between tea intake and dental caries and periodontitis is controversial. We extracted datasets for tea intake and oral diseases from genome-wide association studies (GWASs) conducted by the UK Biobank and the Gene Lifestyle Interactions in Dental Endpoints consortium. We selected 38 single-nucleotide polymorphisms (SNPs) significantly associated with tea intake as instrumental variables (IVs) (P < 5.0 × 10-8). Mendelian randomization (MR) was performed to investigate the potential causality between tea intake and caries and periodontitis. Multivariable Mendelian randomization (MVMR) analyses were utilized to estimate causal effects of tea intake on risk of caries and periodontitis after adjusting for smoking, body mass index (BMI), and socioeconomic factors. The results showed that higher tea intake was suggestively associated with fewer natural teeth (ß = - 0.203; 95% CI = 0.680 to 0.980; P = 0.029) and higher risk of periodontitis (OR = 1.622; 95% CI = 1.194 to 2.205; P = 0.002). After Bonferroni correction, the causality of tea intake on periodontitis remained significant. The significance of periodontitis disappeared after adjusting for the socioeconomic factors in MVMR (OR = 1.603; 95% CI = 0.964 to 2.666; P = 0.069). Tea intake had no association with risk of caries. Statistical insignificance of the heterogeneity test and pleiotropy test supported the validity of the MR study. Our results provide insight into the potential relationship between tea intake and oral diseases from a dietary lifestyle perspective, which may help prevent oral diseases.


Asunto(s)
Caries Dental , Periodontitis , Humanos , Caries Dental/epidemiología , Caries Dental/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Periodontitis/epidemiología , Periodontitis/genética , Polimorfismo de Nucleótido Simple ,
8.
Bioorg Med Chem Lett ; 101: 129653, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38360420

RESUMEN

Gene-encoded aldehyde tag technology has been widely utilized in protein bioorthogonal chemistry and biotechnological application. Herein, we report utilization of the promiscuous rSAM cyclophane synthase SjiB involved in triceptide biosynthesis as a dedicated and highly efficient formylglycine synthase. The new aldehyde tag sequence in this system, YQSSI, is biosynthetically orthogonal to the known aldehyde tag (C/S)x(P/A)xR. The potential use of SjiB/YQSSI aldehyde tag system was further validated in fluorescent labelling of model proteins.


Asunto(s)
Aldehídos , Ciclofanos , Proteínas
9.
Inorg Chem ; 63(10): 4770-4782, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38409795

RESUMEN

Photocatalytic for hydrogen peroxide (H2O2) production is thought as a promising technology owing to its clean and green properties with the cheap and easily available raw materials of H2O and O2. Herein, Pt/g-C3N4 Schottky junction photocatalysts with ultralow Pt contents (0.025-0.1 wt %) were successfully fabricated by an impregnation-reduction method. It can efficiently reduce O2 to generate H2O2 without a sacrificial agent under visible-light irradiation. The yield of H2O2 produced over Pt0.05/g-C3N4 with the optimal 0.05 wt % Pt reached 31.82 µM, which was 2.46 times that of g-C3N4 and higher than most of those in the literature. It also showed good stability in three repeated tests. The deposition of highly dispersed metal Pt nanoparticles with low and limited content can expose enough active Pt atoms, significantly enhance the separation efficiency of photogenerated carriers, and reduce its negative effect on H2O2 decomposition, resulting in improved and outstanding efficiency of H2O2 production. The ·O2- radicals were found to be the main active species. The mechanism of photocatalytic H2O2 production was confirmed to be a two-step single electron route (O2 + e-→ ·O2- → H2O2).

10.
Ecotoxicol Environ Saf ; 272: 116075, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38325273

RESUMEN

Although animal studies have shown the reproductive toxicity of vanadium, less is known about its effects on semen quality in humans. Among 1135 healthy men who were screened as potential semen donors, we investigated the relationships of semen quality with urinary and seminal plasma vanadium levels via inductively coupled plasma-mass spectrometry (ICP-MS). Spearman rank correlation tests and linear regression models were used to assess the correlations between average urinary and within-individual pooled seminal plasma vanadium concentrations (n = 1135). We utilized linear mixed-effects models to evaluate the associations of urinary and seminal plasma vanadium levels (n = 1135) with repeated sperm quality parameters (n = 5576). Seminal plasma vanadium concentrations were not significantly correlated with urinary vanadium concentrations (r = 0.03). After adjusting for possible confounders, we observed inverse relationships of within-individual pooled seminal plasma vanadium levels with total count, semen volume, and sperm concentration (all P values for trend < 0.05). Specifically, subjects in the highest (vs. lowest) tertile of seminal plasma vanadium concentrations had - 11.3% (-16.4%, -5.9%), - 11.1% (-19.1%, -2.4%), and - 20.9% (-29.0%, -11.8%) lower sperm volume, concentration, and total count, respectively; moreover, urinary vanadium levels appeared to be negatively associated with sperm motility. These relationships showed monotonically decreasing dose-response patterns in the restricted cubic spline analyses. Our results demonstrated a poor correlation between urinary and seminal plasma levels of vanadium, and elevated vanadium concentrations in urine and seminal plasma may be adversely related to male semen quality.


Asunto(s)
Análisis de Semen , Semen , Animales , Masculino , Humanos , Semen/química , Vanadio/toxicidad , Vanadio/análisis , Motilidad Espermática , Recuento de Espermatozoides , Espermatozoides/fisiología
11.
Curr Med Chem ; 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38265399

RESUMEN

BACKGROUND: Since December 2019, the emergence of severe acute respiratory syndrome coronavirus 2, which gave rise to coronavirus disease 2019 (COVID-19), has considerably impacted global health. The identification of effective anticoronavirus peptides (ACVPs) and the establishment of robust data storage methods are critical in the fight against COVID-19. Traditional wet-lab peptide discovery approaches are time-- consuming and labor-intensive. With advancements in computer technology and bioinformatics, machine learning has gained prominence in the extraction of functional peptides from extensive datasets. METHODS: In this study, we comprehensively review data resources and predictors related to ACVPs published over the past two decades. In addition, we analyze the influence of various factors on model performance. RESULTS: We have reviewed nine ACVP-containing databases, which integrate detailed information on protein fragments effective against coronaviruses, providing crucial references for the development of antiviral drugs and vaccines. Additionally, we have assessed 15 peptide predictors for antiviral or specifically anticoronavirus activity. These predictors employ computational models to swiftly screen potential antiviral candidates, offering an efficient pathway for drug development. CONCLUSION: Our study provides conclusive results and insights into the performance of different computational methods, and sheds light on the future trajectory of bioinformatics tools for ACVPs. This work offers a representative overview of contributions to the field, with an emphasis on the crucial role of ACVPs in combating COVID-19.

12.
Carbohydr Polym ; 327: 121705, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38171667

RESUMEN

Utilizing renewable natural resources to construct multifunctional packaging materials is critical to achieving sustainable development in the food packaging industry. In this study, we crafted transparent films with comprehensive UV-shielding and antioxidant properties by blending a multicomponent chitosan complex with polyvinyl alcohol (PVA), subsequently applied to preserve peanut butter. The multicomponent chitosan complex, synthesized from chitosan, ferulic acid (FA), and 5-oxo-3,5-dihydro-2H-thiazolo [3,2-a] pyridine-7-carboxylic acid (TPCA) through direct heating in water, served as the foundation. This chitosan complex was seamlessly blended with PVA, resulting in the creation of a transparent film through the solvent casting method. A meticulous investigation into the chemical structure and physicochemical properties of the blended films was conducted. The FA and TPCA components exhibited robust ultraviolet absorption properties, conferring virtually complete full-band ultraviolet shielding ability to the blend film. Additionally, FA endowed the blended film with significant antioxidant activity. The effectiveness of the chitosan complex/PVA blended film in preserving peanut butter from oxidative spoilage was demonstrated, showcasing its robustness in food preservation. Our research underscores the significance of creating advanced packaging materials from sustainable sources.


Asunto(s)
Antioxidantes , Quitosano , Antioxidantes/química , Alcohol Polivinílico/química , Quitosano/química , Embalaje de Alimentos/métodos , Antibacterianos/química
13.
Small ; : e2310341, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38225705

RESUMEN

The safety, low cost, and high power density of aqueous Zn-based devices (AZDs) appeal to large-scale energy storage. Yet, the presence of hydrogen evolution reaction (HER) and chemical corrosion in the AZDs leads to local OH- concentration increasement and the formation of Znx SOy (OH)z •nH2 O (ZHS) by-products at the Zn/electrolyte interface, causing instability and irreversibility of the Zn-anodes. Here, a strategy is proposed to regulate OH- by introducing a bio-sourced/renewable polypeptide (ɛ-PL) as a pH regulator in electrolyte. The consumption of OH- species is evaluated through in vitro titration and cell in vivo in situ attenuated total reflection surface-enhanced infrared absorption spectroscopy at a macroscopic and molecular level. The introduction of ɛ-PL is found to significantly suppress the formation of ZHS and associated side reactions, and reduce the local coordinated H2 O of the Zn2+ solvation shell, widening electrochemical stable window and suppressing OH- generation during HER. As a result, the inclusion of ɛ-PL improves the cycle time of Zn/Zn symmetrical cells from 15 to 225 h and enhances the cycle time of aqueous Zn- I2 cells to 1650 h compared to those with pristine electrolytes. This work highlights the potential of kinetical OH- regulation for by-product and dendrite-free AZDs.

14.
BMC Public Health ; 24(1): 187, 2024 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-38225595

RESUMEN

BACKGROUND: Magnesium (Mg) is both an essential macro-element and a known catalyst, and it plays a vital role in various physiological activities and mechanisms in relation to chronic kidney disease (CKD). However, epidemiological evidence involving this is limited and not entirely consistent. This study aims to explore the association of serum Mg concentrations with the risk of CKD among general Chinese adults. METHODS: A total of 8,277 Chinese adults were included in the wave of 2009 from the China Health and Nutrition Survey (CHNS). The primary outcome was the risk of CKD, which was defined as the estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Multivariable logistic regression model was used to examine the relationship of serum Mg concentrations with the risk of CKD. RESULTS: Included were 8,277 individuals, with an overall CKD prevalence of 11.8% (n = 977). Compared with the first quartile of serum Mg, the multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for participants in the second, third, and fourth quartiles of serum Mg were 0.74 (0.58, 0.93), 0.87 (0.69, 1.11) and 1.29 (1.03, 1.61), respectively. Similar results were observed in our several sensitivity analyses. Restricted cubic spline analysis demonstrated a nonlinear (similar "J"-shaped) association between serum Mg concentrations and the risk of CKD (Pnonlinearity <0.001), with a threshold at around a serum Mg value of 2.2 mg/dL. CONCLUSIONS: Our results suggested a similar "J"-shaped association between serum Mg concentration and the risk of CKD among Chinese adults. Further large prospective studies are needed to verify these findings.


Asunto(s)
Magnesio , Insuficiencia Renal Crónica , Adulto , Humanos , Estudios Transversales , Insuficiencia Renal Crónica/epidemiología , Tasa de Filtración Glomerular , Encuestas Epidemiológicas , Factores de Riesgo
15.
Int J Cancer ; 154(9): 1616-1625, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38216995

RESUMEN

Anti-human epidermal growth factor receptor 2 (HER2) agents have exhibited pronounced tumor-inhibitory activity, yet the accompanying ocular toxicity has frequently been underestimated. We aim to conduct a comprehensive comparative analysis of ocular toxicity risk related to various anti-HER2 agents. We executed a retrospective pharmacovigilance investigation based on the FDA Adverse Event Reporting System (FAERS) database, covering the period from Q2 2018 to Q1 2023. The disproportionality analysis was performed to assess ocular toxicity risk. Multivariate logistic regression was implemented to mitigate potential biases. Moreover, the time to onset of ocular toxicity was also evaluated. A total of 3467 ocular adverse event (AE) reports concerning anti-HER2 agents were collected. At the preferred term (PT) level, there were 69 positive signals, among which excessive eye blinking, abnormal sensation in the eye, and asthenopia presented a significant risk. In comparison to tyrosine kinase inhibitors (TKIs), antibody drugs were associated with a broader range of ocular disorders at Standardized MedDRA Queries (SMQ)levels, including conjunctival disorders, corneal disorders, ocular infections, ocular motility disorders, optic nerve disorders, and retinal disorders. In terms of onset time, pertuzumab displayed an earlier onset at 21.5 days, while trastuzumab deruxtecan had the latest at 91.5 days. In summary, our study reveals varying degrees of ocular toxicity related to anti-HER2 agents, with a significantly higher risk observed in antibody drugs. Additionally, novel ocular toxicity signals, not documented in product labels, have been detected. In the future, further research will be necessary to validate our findings.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neuropatía Óptica Tóxica , Farmacovigilancia , Estudios Retrospectivos , Bases de Datos Factuales , Sistemas de Registro de Reacción Adversa a Medicamentos
16.
Ecotoxicol Environ Saf ; 269: 115740, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38042131

RESUMEN

Triazine herbicides are common contaminants in coastal waters, and they are recognized as inhibitors of photosystem II, causing significant hinderance to the growth and reproduction of phytoplankton. However, the influence of these herbicides on microalgal toxin production remains unclear. This study aimed to examine this relationship by conducting a comprehensive physiological and 4D label-free quantitative proteomic analysis on the harmful dinoflagellate Karenia mikimotoi in the presence of the triazine herbicide dipropetryn. The findings demonstrated a significant decrease in photosynthetic activity and pigment content, as well as reduced levels of unsaturated fatty acids, reactive oxygen species (ROS), and hemolytic toxins in K. mikimotoi when exposed to dipropetryn. The proteomic analysis revealed a down-regulation in proteins associated with photosynthesis, ROS response, and energy metabolism, such as fatty acid biosynthesis, chlorophyll metabolism, and nitrogen metabolism. In contrast, an up-regulation of proteins related to energy-producing processes, such as fatty acid ß-oxidation, glycolysis, and the tricarboxylic acid cycle, was observed. This study demonstrated that dipropetryn disrupts the photosynthetic systems of K. mikimotoi, resulting in a notable decrease in algal toxin production. These findings provide valuable insights into the underlying mechanisms of toxin production in toxigenic microalgae and explore the potential effect of herbicide pollution on harmful algal blooms in coastal environments.


Asunto(s)
Dinoflagelados , Herbicidas , Microalgas , Especies Reactivas de Oxígeno/metabolismo , Proteómica , Dinoflagelados/metabolismo , Floraciones de Algas Nocivas , Fotosíntesis , Herbicidas/metabolismo , Ácidos Grasos/metabolismo , Triazinas/toxicidad , Triazinas/metabolismo
17.
Artículo en Inglés | MEDLINE | ID: mdl-38154516

RESUMEN

BACKGROUND: Several observational studies have suggested that oral anticoagulants (OACs) might reduce the risk of dementia in the elderly, but the evidence is inconclusive. And the consistency of this relationship across different OAC classes and dementia subtypes is still uncertain. METHODS: To comprehensively evaluate this association, we applied Mendelian randomization (MR) combined with pharmacovigilance analysis. MR was used to assess the associations between genetic proxies for three target genes of OACs (VKORC1, F2, and F10) and dementia, including Alzheimer's disease (AD) and vascular dementia (VaD). This genetic analysis was supplemented with real-world pharmacovigilance data, employing disproportionality analysis for more reliable causal inference. RESULTS: Increased expression of the VKORC1 gene was strongly associated with increased risk of dementia, especially for AD (OR = 1.28, 95% CI = 1.14-1.43; p value < 0.001). Based on pharmacovigilance data, vitamin K antagonists (VKAs, inhibitors targeting VKORC1) exhibited a protective effect against dementia risk (ROR = 0.43, 95% CI = 0.28-0.67). Additional sensitivity analyses, including different MR models and cohorts, supported these results. Conversely, no strong causal associations of genetically proxied F2 and F10 target genes with dementia and its subtypes were found. CONCLUSIONS: This study reveals that the inhibition of genetically proxied VKORC1 expression or VKAs exposure is associated with a reduced risk of Alzheimer's dementia. However, there is little evidence to support similar associations with direct oral anticoagulants (F2 inhibitors and F10 inhibitors). Further research is warranted to clinically validate our findings.


Asunto(s)
Enfermedad de Alzheimer , Demencia , Humanos , Anciano , Administración Oral , Anticoagulantes/efectos adversos , Demencia/epidemiología , Demencia/genética , Demencia/inducido químicamente , Genómica , Estudio de Asociación del Genoma Completo , Enfermedad de Alzheimer/tratamiento farmacológico , Vitamina K Epóxido Reductasas
18.
Sci Rep ; 13(1): 21916, 2023 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-38081931

RESUMEN

Gankyrin is found in high levels in triple-negative breast cancer (TNBC) and has been established to form a complex with the E3 ubiquitin ligase MDM2 and p53, resulting in the degradation of p53 in hepatocarcinoma cells. Therefore, this study sought to determine whether gankyrin could inhibit ferroptosis through this mechanism in TNBC cells. The expression of gankyrin was investigated in relation to the prognosis of TNBC using bioinformatics. Co-immunoprecipitation and GST pull-down assays were then conducted to determine the presence of a gankyrin and MDM2 complex. RT-qPCR and immunoblotting were used to examine molecules related to ferroptosis, such as gankyrin, p53, MDM2, SLC7A11, and GPX4. Additionally, cell death was evaluated using flow cytometry detection of 7-AAD and a lactate dehydrogenase release assay, as well as lipid peroxide C11-BODIPY. Results showed that the expression of gankyrin is significantly higher in TNBC tissues and cell lines, and is associated with a poor prognosis for patients. Subsequent studies revealed that inhibiting gankyrin activity triggered ferroptosis in TNBC cells. Additionally, silencing gankyrin caused an increase in the expression of the p53 protein, without altering its mRNA expression. Co-immunoprecipitation and GST pull-down experiments indicated that gankyrin and MDM2 form a complex. In mouse embryonic fibroblasts lacking both MDM2 and p53, this gankyrin/MDM2 complex was observed to ubiquitinate p53, thus raising the expression of molecules inhibited by ferroptosis, such as SLC7A11 and GPX4. Furthermore, silencing gankyrin in TNBC cells disrupted the formation of the gankyrin/MDM2 complex, hindered the degradation of p53, increased SLC7A11 expression, impeded cysteine uptake, and decreased GPX4 production. Our findings suggest that TNBC cells are able to prevent cell ferroptosis through the gankyrin/p53/SLC7A11/GPX4 signaling pathway, indicating that gankyrin may be a useful biomarker for predicting TNBC prognosis or a potential therapeutic target.


Asunto(s)
Ferroptosis , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Fibroblastos/metabolismo , Sistema de Transporte de Aminoácidos y+/genética
19.
Clin Exp Med ; 23(8): 4623-4632, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37925379

RESUMEN

Acute myeloid leukemia (AML) is a malignant hematological neoplastic disease. Autocrine or paracrine cytokines released by leukemic cells regulate the proliferation of AML cells. It is uncertain whether cytokines can indicate whether patients with AML are in remission with chemotherapy. The goal of this study was to evaluate the levels of Th1/Th2/Th17 cytokines in AML patients before and after chemotherapy to determine whether the cytokine levels could predict disease remission after chemotherapy. It was found that the levels of IL-5, IL-6, IL-8, IL-10, TNF-α, TNF-ß, IL-17F, and IL-22 were significantly increased at the time of AML diagnosis in patients who achieved remission after two chemotherapy treatments (P < 0.05). After chemotherapy, the cytokine levels were reduced in patients with remission, while the levels of IL-6 and IL-8 were raised in patients without remission (P < 0.05). A comparison of cytokine levels before and after chemotherapy in patients who achieved remission showed areas under the curve (AUCs) of 0.69 for both IL-6 and IL-8. In addition, a comparison of the remission and non-remission groups after chemotherapy showed an AUC of 0.77 for IL-6. We then calculated the cutoff value using receiver operating characteristic curves. Values of IL-6 < 9.99 and IL-8 < 8.46 at the time of diagnosis were predictive of chemotherapy success and remission, while IL-6 > 14.89 at diagnosis suggested that chemotherapy would not be successful and remission would not be achieved. Multifactorial analysis showed that age, Neu, IL-6, and IL-8 were independent risk factors for AML prognosis, and IL-6 (OR = 5.48, P = 0.0038) was superior to age (OR = 3.36, P = 0.0379), Neu (OR = 0.28, P = 0.0308), IL-8 (OR = 0.0421, P = 0.0421). In conclusion, IL-6 levels were found to be predictive of the likelihood of remission.


Asunto(s)
Citocinas , Leucemia Mieloide Aguda , Humanos , Interleucina-6 , Interleucina-8 , Inducción de Remisión , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Pronóstico
20.
Environ Sci Pollut Res Int ; 30(60): 125677-125688, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38001293

RESUMEN

The treatment of cooking oil wastewater is an urgent issue need to be solved. We aimed to screen for efficient oil-degrading bacteria and develop a new microbial agent for degrading waste cooking oil in oily wastewater. Three extremely effective oil-degrading bacteria, known as YZQ-1, YZQ-3, and YZQ-4, were found by the enrichment and acclimation of samples from various sources and separation using oil degradation plates. The 16S rRNA sequencing analysis and phylogenetic tree construction showed that the three strains were Bacillus tropicus, Pseudomonas multiresinivorans, and Raoultella terrigena. Under optimal degradation conditions, the maximal degradation rates were 67.30 ± 3.69%, 89.65 ± 1.08%, and 79.60 ± 5.30%, respectively, for YZQ-1, YZQ-3, and YZQ-4. Lipase activity was highest for YZQ-3, reaching 94.82 ± 12.89 U/L. The best bacterial alliance was obtained by adding equal numbers of microbial cells from the three strains. Moreover, when this bacterial alliance was applied to oily wastewater, the degradation rate of waste cooking oil was 61.13 ± 7.30% (3.67% ± 2.13% in the control group), and COD removal was 62.4% ± 5.65% (55.60% ± 0.71% in the control group) in 72 h. Microbial community analysis results showed YZQ-1 and YZQ-3 were adaptable to wastewater and could coexist with local bacteria, whereas YZQ-4 could not survive in wastewater. Therefore, the combination of YZQ-1 and YZQ-3 can efficiently degrade oil and shows great potential for oily wastewater treatment.


Asunto(s)
Aceites , Aguas Residuales , ARN Ribosómico 16S/metabolismo , Filogenia , Bacterias/metabolismo , Biodegradación Ambiental
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