Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 212
Filtrar
1.
Pol J Pathol ; 75(2): 83-96, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39166517

RESUMEN

There is growing evidence that the KDM5 family of histone demethylases plays a causal role in human cancer. However, few studies have been reported on the KDM5 family in endometrial carcinoma (EC). Moreover, it was found that there was some correlation between the KDM5 family and FOXO1 in EC. The current study was performed to explore the expressions of KDM5A, KDM5B, and FOXO1 in endometrioid adenocarcinoma detected by immunohistochemistry; paracancer endometrium, simple hyperplastic endometrium, and normal endometrium were used as control groups to explore the possible diagnostic value of KDM5A and KDM5B expression in endometrioid adenocarcinoma, with the aim of evaluating the potential of this marker in predicting the prognosis of endometrioid adenocarcinoma.


Asunto(s)
Biomarcadores de Tumor , Carcinoma Endometrioide , Neoplasias Endometriales , Proteína Forkhead Box O1 , Inmunohistoquímica , Histona Demetilasas con Dominio de Jumonji , Humanos , Neoplasias Endometriales/patología , Neoplasias Endometriales/metabolismo , Femenino , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Persona de Mediana Edad , Histona Demetilasas con Dominio de Jumonji/metabolismo , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/metabolismo , Adulto , Anciano , Pronóstico , Proteína 2 de Unión a Retinoblastoma/metabolismo , Proteína 2 de Unión a Retinoblastoma/análisis , Relevancia Clínica , Proteínas Nucleares , Proteínas Represoras
2.
Front Immunol ; 15: 1418897, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39148726

RESUMEN

Mast cells (MCs) are bone-marrow-derived haematopoietic cells that are widely distributed in human tissues. When activated, they will release tryptase, histamine and other mediators that play major roles in a diverse array of diseases/disorders, including allergies, inflammation, cardiovascular diseases, autoimmune diseases, cancers and even death. The multiple pathological effects of MCs have made their stabilizers a research hotspot for the treatment of related diseases. To date, the clinically available MC stabilizers are limited. Considering the rapidly increasing incidence rate and widespread prevalence of MC-related diseases, a comprehensive reference is needed for the clinicians or researchers to identify and choose efficacious MC stabilizers. This review analyzes the mechanism of MC activation, and summarizes the progress made so far in the development of MC stabilizers. MC stabilizers are classified by the action mechanism here, including acting on cell surface receptors, disturbing signal transduction pathways and interfering exocytosis systems. Particular emphasis is placed on the clinical applications and the future development direction of MC stabilizers.


Asunto(s)
Mastocitos , Humanos , Mastocitos/inmunología , Mastocitos/metabolismo , Mastocitos/efectos de los fármacos , Animales , Transducción de Señal , Terapia Molecular Dirigida
3.
IEEE Trans Image Process ; 33: 4568-4583, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39150807

RESUMEN

High-quality panoramic images with a Field of View (FoV) of 360° are essential for contemporary panoramic computer vision tasks. However, conventional imaging systems come with sophisticated lens designs and heavy optical components. This disqualifies their usage in many mobile and wearable applications where thin and portable, minimalist imaging systems are desired. In this paper, we propose a Panoramic Computational Imaging Engine (PCIE) to achieve minimalist and high-quality panoramic imaging. With less than three spherical lenses, a Minimalist Panoramic Imaging Prototype (MPIP) is constructed based on the design of the Panoramic Annular Lens (PAL), but with low-quality imaging results due to aberrations and small image plane size. We propose two pipelines, i.e. Aberration Correction (AC) and Super-Resolution and Aberration Correction (SR&AC), to solve the image quality problems of MPIP, with imaging sensors of small and large pixel size, respectively. To leverage the prior information of the optical system, we propose a Point Spread Function (PSF) representation method to produce a PSF map as an additional modality. A PSF-aware Aberration-image Recovery Transformer (PART) is designed as a universal network for the two pipelines, in which the self-attention calculation and feature extraction are guided by the PSF map. We train PART on synthetic image pairs from simulation and put forward the PALHQ dataset to fill the gap of real-world high-quality PAL images for low-level vision. A comprehensive variety of experiments on synthetic and real-world benchmarks demonstrates the impressive imaging results of PCIE and the effectiveness of the PSF representation. We further deliver heuristic experimental findings for minimalist and high-quality panoramic imaging, in terms of the choices of prototype and pipeline, network architecture, training strategies, and dataset construction. Our dataset and code will be available at https://github.com/zju-jiangqi/PCIE-PART.

4.
Front Immunol ; 15: 1381735, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38840923

RESUMEN

Background: Acute liver injury (ALI), which is a type of inflammation-mediated hepatocellular injury, is a clinical syndrome that results from hepatocellular apoptosis and hemorrhagic necrosis. Apoptosis stimulating protein of p53-2 (ASPP2) is a proapoptotic member of the p53 binding protein family. However, the role of ASPP2 in the pathogenesis of ALI and its regulatory mechanisms remain unclear. Methods: The expression of ASPP2 were compared between liver biopsies derived from patients with CHB, patients with ALI, and normal controls. Acute liver injury was modelled in mice by administration of D-GalN/LPS. Liver injury was demonstrated by serum transaminases and histological assessment of liver sections. ASPP2-knockdown mice (ASPP2+/-) were used to determine its role in acute liver injury. Mouse bone marrow macrophages (BMMs) were isolated from wildtype and ASPP2+/- mice and stimulated with LPS, and the supernatant was collected to incubate with the primary hepatocytes. Quantitative real-time PCR and western blot were used to analyze the expression level of target. Results: The expression of ASPP2 was significantly upregulated in the liver tissue of ALI patients and acute liver injury mice. ASPP2+/- mice significantly relieved liver injury through reducing liver inflammation and decreasing hepatocyte apoptosis. Moreover, the conditioned medium (CM) of ASPP2+/- bone marrow-derived macrophages (BMMs) protected hepatocytes against apoptosis. Mechanistically, we revealed that ASPP2 deficiency in BMMs specifically upregulated IL-6 through autophagy activation, which decreased the level of TNF-α to reduce hepatocytes apoptosis. Furthermore, up-regulation of ASPP2 sensitizes hepatocytes to TNF-α-induced apoptosis. Conclusion: Our novel findings show the critical role of ASPP2 in inflammatory immunoregulatory mechanism of ALI and provide a rationale to target ASPP2 as a refined therapeutic strategy to ameliorate acute liver injury.


Asunto(s)
Proteínas Reguladoras de la Apoptosis , Apoptosis , Animales , Humanos , Ratones , Masculino , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Ratones Noqueados , Hígado/patología , Hígado/metabolismo , Hígado/inmunología , Hepatocitos/metabolismo , Hepatocitos/patología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Inflamación/inmunología , Inflamación/metabolismo , Femenino , Lipopolisacáridos , Persona de Mediana Edad , Macrófagos/inmunología , Macrófagos/metabolismo , Adulto , Proteínas Supresoras de Tumor
5.
6.
BMC Immunol ; 25(1): 26, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702611

RESUMEN

BACKGROUND: Early-onset schizophrenia (EOS) is a type of schizophrenia (SCZ) with an age of onset of < 18 years. An abnormal inflammatory immune system may be involved in the occurrence and development of SCZ. We aimed to identify the immune characteristic genes and cells involved in EOS and to further explore the pathogenesis of EOS from the perspective of immunology. METHODS: We obtained microarray data from a whole-genome mRNA expression in peripheral blood mononuclear cells (PBMCs); 19 patients with EOS (age range: 14.79 ± 1.90) and 18 healthy controls (HC) (age range: 15.67 ± 2.40) were involved. We screened for differentially expressed genes (DEGs) using the Limma software package and modular genes using weighted gene co-expression network analysis (WGCNA). In addition, to identify immune characteristic genes and cells, we performed enrichment analysis, immune infiltration analysis, and receiver operating characteristic (ROC) curve analysis; we also used a random forest (RF), a support vector machine (SVM), and the LASSO-Cox algorithm. RESULTS: We selected the following immune characteristic genes: CCL8, PSMD1, AVPR1B and SEMG1. We employed a RF, a SVM, and the LASSO-Cox algorithm. We identified the following immune characteristic cells: activated mast cells, CD4+ memory resting T cells, resting mast cells, neutrophils and CD4+ memory activated T cells. In addition, the AUC values of the immune characteristic genes and cells were all > 0.7. CONCLUSION: Our results indicate that immune system function is altered in SCZ. In addition, CCL8, PSMD1, AVPR1B and SEMG1 may regulate peripheral immune cells in EOS. Further, immune characteristic genes and cells are expected to be diagnostic markers and therapeutic targets of SCZ.


Asunto(s)
Leucocitos Mononucleares , Esquizofrenia , Humanos , Esquizofrenia/inmunología , Esquizofrenia/genética , Masculino , Femenino , Adolescente , Leucocitos Mononucleares/inmunología , Perfilación de la Expresión Génica , Edad de Inicio , Redes Reguladoras de Genes , Quimiocina CCL8/genética , Sistema Inmunológico , Curva ROC , Máquina de Vectores de Soporte
7.
BMC Psychiatry ; 24(1): 299, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38641826

RESUMEN

BACKGROUND: Despite ongoing research, the underlying causes of schizophrenia remain unclear. Aspartate and asparagine, essential amino acids, have been linked to schizophrenia in recent studies, but their causal relationship is still unclear. This study used a bidirectional two-sample Mendelian randomization (MR) method to explore the causal relationship between aspartate and asparagine with schizophrenia. METHODS: This study employed summary data from genome-wide association studies (GWAS) conducted on European populations to examine the correlation between aspartate and asparagine with schizophrenia. In order to investigate the causal effects of aspartate and asparagine on schizophrenia, this study conducted a two-sample bidirectional MR analysis using genetic factors as instrumental variables. RESULTS: No causal relationship was found between aspartate and schizophrenia, with an odds ratio (OR) of 1.221 (95%CI: 0.483-3.088, P-value = 0.674). Reverse MR analysis also indicated that no causal effects were found between schizophrenia and aspartate, with an OR of 0.999 (95%CI: 0.987-1.010, P-value = 0.841). There is a negative causal relationship between asparagine and schizophrenia, with an OR of 0.485 (95%CI: 0.262-0.900, P-value = 0.020). Reverse MR analysis indicates that there is no causal effect between schizophrenia and asparagine, with an OR of 1.005(95%CI: 0.999-1.011, P-value = 0.132). CONCLUSION: This study suggests that there may be a potential risk reduction for schizophrenia with increased levels of asparagine, while also indicating the absence of a causal link between elevated or diminished levels of asparagine in individuals diagnosed with schizophrenia. There is no potential causal relationship between aspartate and schizophrenia, whether prospective or reverse MR. However, it is important to note that these associations necessitate additional research for further validation.


Asunto(s)
Asparagina , Esquizofrenia , Humanos , Asparagina/genética , Ácido Aspártico/genética , Esquizofrenia/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Estudios Prospectivos
8.
Melanoma Res ; 34(4): 376-381, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38647119

RESUMEN

The aim of this study was to determine whether the pretreatment CD8 + PD-1 + to CD4 + PD-1 + (PERLS) ratio is an independent risk prognostic factor of advanced melanoma patients. We retrospectively analyzed the efficacy and flow cytometry data from advanced melanoma patients who received PD-1 inhibitor as monotherapy between January 1, 2018 and January 26, 2022. Fifty-nine patients were enrolled, the PERLS cutoff was 1.125. PERLS did not correlate with clinical characteristics but were significantly associated with baseline CD8 + , CD4 + , and CD8 + PD-1 + T cells. The mean overall survival and the progression-free survival were 45.8 and 17.1 months for the low PERLS group (n = 39), compared with 29.9 ( P  = 0.001) and 9.7 ( P  = 0.003) months for the high PERLS group ( n  = 20), respectively. Pretreatment PERLS might contribute to selecting patients before receiving anti-PD-1 therapy.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Melanoma , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Estudios Retrospectivos , Anciano , Adulto , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD4-Positivos/inmunología , Anciano de 80 o más Años , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores
9.
Fish Physiol Biochem ; 50(3): 1265-1279, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38568383

RESUMEN

Fish typically adapt to their environment through evolutionary traits, and this adaptive strategy plays a critical role in promoting species diversity. Onychostoma macrolepis is a rare and endangered wild species that exhibits a life history of overwintering in caves and breeding in mountain streams. We analyzed the morphological characteristics, histological structure, and expression of circadian clock genes in O. macrolepis to elucidate its adaptive strategies to environmental changes in this study. The results showed that the relative values of O. macrolepis eye diameter, body height, and caudal peduncle height enlarged significantly during the breeding period. The outer layer of the heart was dense; the ventricular myocardial wall was thickened; the fat was accumulated in the liver cells; the red and white pulp structures of the spleen, renal tubules, and glomeruli were increased; and the goblet cells of the intestine were decreased in the breeding period. In addition, the spermatogenic cyst contained mature sperm, and the ovaries were filled with eggs at various stages of development. Throughout the overwintering period, the melano-macrophage center is located between the spleen and kidney, and the melano-macrophage center in the cytoplasm has the ability to synthesize melanin, and is arranged in clusters to form cell clusters or white pulp scattered in it. Circadian clock genes were identified in all organs, exhibiting significant differences between the before/after overwintering period and the breeding period. These findings indicate that the environment plays an important role in shaping the behavior of O. macrolepis, helping the animals to build self-defense mechanisms during cyclical habitat changes. Studying the morphological, histological structure and circadian clock gene expression of O. macrolepis during the overwintering and breeding periods is beneficial for understanding its unique hibernation behavior in caves. Additionally, it provides an excellent biological sample for investigating the environmental adaptability of atypical cavefish species.


Asunto(s)
Adaptación Fisiológica , Relojes Circadianos , Cyprinidae , Relojes Circadianos/genética , Cyprinidae/anatomía & histología , Cyprinidae/genética , Cyprinidae/fisiología , Cruzamiento , Conducta Sexual Animal/fisiología , Adaptación Fisiológica/fisiología , Animales , Masculino , Femenino , Estaciones del Año , Hígado/metabolismo , Bazo , Riñón , Proteínas de Peces/genética , Expresión Génica/fisiología
10.
J Am Chem Soc ; 146(18): 12723-12733, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38654452

RESUMEN

Enfumafungin-type antibiotics, represented by enfumafungin and fuscoatroside, belong to a distinct group of triterpenoids derived from fungi. These compounds exhibit significant antifungal properties with ibrexafungerp, a semisynthetic derivative of enfumafungin, recently gaining FDA's approval as the first oral antifungal drug for treating invasive vulvar candidiasis. Enfumafungin-type antibiotics possess a cleaved E-ring with an oxidized carboxyl group and a reduced methyl group at the break site, suggesting unprecedented C-C bond cleavage chemistry involved in their biosynthesis. Here, we show that a 4-gene (fsoA, fsoD, fsoE, fsoF) biosynthetic gene cluster is sufficient to yield fuscoatroside by heterologous expression in Aspergillus oryzae. Notably, FsoA is an unheard-of terpene cyclase-glycosyltransferase fusion enzyme, affording a triterpene glycoside product that relies on enzymatic fusion. FsoE is a P450 enzyme that catalyzes successive oxidation reactions at C19 to facilitate a C-C bond cleavage, producing an oxidized carboxyl group and a reduced methyl group that have never been observed in known P450 enzymes. Our study thus sets the important foundation for the manufacture of enfumafungin-type antibiotics using biosynthetic approaches.


Asunto(s)
Antifúngicos , Antifúngicos/química , Antifúngicos/farmacología , Antifúngicos/metabolismo , Aspergillus oryzae/enzimología , Aspergillus oryzae/metabolismo , Familia de Multigenes , Triterpenos/química , Triterpenos/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo
11.
PLoS One ; 19(4): e0300284, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38635789

RESUMEN

This study aimed to examine the impact and source of announcements introducing additional long-term shareholder perks on stock prices of Japanese listed companies. We produced more precise analysis results by categorizing the total sample into favorable change and unfavorable change sample. As a result, we found that long-term shareholder perks have a positive impact on stock prices through the expansion of the shareholder base in the case of a favorable change, whereas there is no negative impact on stock liquidity due to an increased number of long term individual shareholders. On the contrary, in the case of an unfavorable change, we found a weak trend of shrinkage in the shareholder base due to individual shareholders' defection and a consequent decrease in stock liquidity. In the case of a favorable change, the long-term shareholder perks program functions as a means to increase the number of shareholders and encourage them to hold the shares for a longer period of time.


Asunto(s)
Renta , Inversiones en Salud
12.
Front Genet ; 15: 1346150, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38444759

RESUMEN

DNA methylation is influenced by various exogenous factors such as nutrition, temperature, toxicants, and stress. Bulls from the Pacific Northwest region of the United States and other northern areas are exposed to extreme cold temperatures during winter. However, the effects of cold exposure on the methylation patterns of bovine sperm remain unclear. To address, DNA methylation profiles of sperm collected during late spring and winter from the same bulls were analyzed using whole genome bisulfite sequencing (WGBS). Bismark (0.22.3) were used for mapping the WGBS reads and R Bioconductor package DSS was used for differential methylation analysis. Cold exposure induced 3,163 differentially methylated cytosines (DMCs) with methylation difference ≥10% and a q-value < 0.05. We identified 438 differentially methylated regions (DMRs) with q-value < 0.05, which overlapped with 186 unique genes. We also identified eight unique differentially methylated genes (DMGs) (Pax6, Macf1, Mest, Ubqln1, Smg9, Ctnnb1, Lsm4, and Peg10) involved in embryonic development, and nine unique DMGs (Prmt6, Nipal1, C21h15orf40, Slc37a3, Fam210a, Raly, Rgs3, Lmbr1, and Gan) involved in osteogenesis. Peg10 and Mest, two paternally expressed imprinted genes, exhibited >50% higher methylation. The differential methylation patterns of six distinct DMRs: Peg10, Smg9 and Mest related to embryonic development and Lmbr1, C21h15orf40 and Prtm6 related to osteogenesis, were assessed by methylation-specific PCR (MS-PCR), which confirmed the existence of variable methylation patterns in those locations across the two seasons. In summary, cold exposure induces differential DNA methylation patterns in genes that appear to affect embryonic development and osteogenesis in the offspring. Our findings suggest the importance of replicating the results of the current study with a larger sample size and exploring the potential of these changes in affecting offspring development.

13.
Nano Lett ; 24(12): 3638-3646, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38498912

RESUMEN

Tin-based two-dimensional (2D) perovskites are emerging as lead-free alternatives in halide perovskite materials, yet their exciton dynamics and transport remain less understood due to defect scattering. Addressing this, we employed temperature-dependent transient photoluminescence (PL) microscopy to investigate intrinsic exciton transport in three structurally analogous Sn- and Pb-based 2D perovskites. Employing conjugated ligands, we synthesized high-quality crystals with enhanced phase stability at various temperatures. Our results revealed phonon-limited exciton transport in Sn perovskites, with diffusion constants increasing from 0.2 cm2 s-1 at room temperature to 0.6 cm2 s-1 at 40 K, and a narrowing PL line width. Notably, Sn-based perovskites exhibited greater exciton mobility than their Pb-based equivalents, which is attributed to lighter effective masses. Thermally activated optical phonon scattering was observed in Sn-based compounds but was absent in Pb-based materials. These findings, supported by molecular dynamics simulations, demonstrate that the phonon scattering mechanism in Sn-based halide perovskites can be distinct from their Pb counterparts.

14.
Comput Methods Programs Biomed ; 247: 108083, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38402715

RESUMEN

BACKGROUND: This study is undertaken to establish the accuracy and reliability of OrthoCalc, a 3D application designed for the evaluation of maxillary positioning. METHODS: We registered target virtual planned models, maxillary models from pre-operative and post-operative CT scans, and post-operative intra-oral scans to a common reference system, allowing for digital evaluation. To assess rotational changes, we introduced a novel measurement method based on virtual cuboid models. Displacement errors were calculated based on proposed registration matrices. We also compared OrthoCalc to established commercial medical software as a benchmark. RESULTS: Statistical significance calculated showed no significant differences between OrthoCalc and commercial software. the biggest error of 0.04 degree in rotation change was found in the yaw. A maximum displacement change of 0.75 mm was found in the X direction. CONCLUSIONS: Our study validates OrthoCalc as a precise and reliable tool for assessing maxillary position changes with six degrees of freedom in orthognathic surgery, endorsing its clinical utility.


Asunto(s)
Procedimientos Quirúrgicos Ortognáticos , Cirugía Asistida por Computador , Procedimientos Quirúrgicos Ortognáticos/métodos , Maxilar/diagnóstico por imagen , Reproducibilidad de los Resultados , Flujo de Trabajo , Programas Informáticos , Imagenología Tridimensional/métodos , Cirugía Asistida por Computador/métodos
15.
Sci Total Environ ; 918: 170675, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38316312

RESUMEN

The early stage of heart development is highly susceptible to various environmental factors. While the use of animal models has aided in identifying numerous environmental risk factors, the variability between species and the low throughput limit their translational potential. Recently, a type of self-assembling cardiac structures, known as human heart organoids (hHOs), exhibits a remarkable biological consistency with human heart. However, the feasibility of hHOs for assessing cardiac developmental risk factors remains unexplored. Here, we focused on the cardiac developmental effects of core components of Glyphosate-based herbicides (GBHs), the most widely used herbicides, to evaluate the reliability of hHOs for the prediction of possible cardiogenesis toxicity. GBHs have been proven toxic to cardiac development based on multiple animal models, with the mechanism remaining unknown. We found that polyoxyethylene tallow amine (POEA), the most common surfactant in GBHs formulations, played a dominant role in GBHs' heart developmental toxicity. Though there were a few differences in transcriptive features, hHOs exposed to sole POEA and combined POEA and Glyphosate would suffer from both disruption of heart contraction and disturbance of commitment in cardiomyocyte isoforms. By contrast, Glyphosate only caused mild epicardial hyperplasia. This study not only sheds light on the toxic mechanism of GBHs, but also serves as a methodological demonstration, showcasing its effectiveness in recognizing and evaluating environmental risk factors, and deciphering toxic mechanisms.


Asunto(s)
Grasas , Glifosato , Herbicidas , Animales , Humanos , Aminas , Glicina/toxicidad , Glicina/química , Reproducibilidad de los Resultados , Polietilenglicoles/química , Herbicidas/toxicidad , Herbicidas/química
16.
Nitric Oxide ; 145: 33-40, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38382866

RESUMEN

OBJECTIVE: Hydrogen sulfide (H2S) is associated with depressive-like behavior in rodents. We undertook cross-sectional and longitudinal analyses of plasma levels of H2S and its substrate homocysteine (Hcy) in depression and assessed the association of both parameters with psychopathology and cognitive function. METHODS: Forty-one patients suffering from depression (PSDs) and 48 healthy volunteers were recruited. PSDs were treated for 8 weeks. Analyzable data were collected from all participants for assessment of their psychopathology and cognitive function. Plasma was collected for determination of levels of H2S and Hcy, and data were correlated to determine their potential as plasma biomarkers. RESULTS: Cross-sectional analyses revealed PSDs to have a low plasma H2S level and high Hcy level. Longitudinal analyses revealed that 8 weeks of treatment reversed the changes in plasma levels of H2S and Hcy in PSDs. Plasma levels of H2S and Hcy were associated with psychopathology and cognitive function in depression. The area under the receiver operating characteristic curve (AUC) for a combination of plasma levels of H2S and Hcy and expression of the TNF gene (i.e., H2S-Hcy-TNF) was 0.848 for diagnosing depression and 0.977 for predicting the efficacy of antidepressant agents. CONCLUSION: Plasma levels of H2S and Hcy reflect changes in psychopathology and cognitive function in depression and H2S-Hcy-TNF has the potential to diagnose depression and predict the efficacy of antidepressant medications.


Asunto(s)
Sulfuro de Hidrógeno , Humanos , Sulfuro de Hidrógeno/metabolismo , Estudios Transversales , Homocisteína
17.
Sci Rep ; 14(1): 4292, 2024 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-38383617

RESUMEN

Currently, the relationship between serum uric acid (SUA) and bone mineral density (BMD) in men remains controversial. This study aims to investigate the relationship between SUA and lumbar spine BMD in American men using data from the National Health and Nutrition Examination Survey (NHANES). A total of 6254 male subjects aged 12-80 years (mean age 35.52 ± 14.84 years) in the NHANES from 2011 to 2020 were analyzed. SUA was measured by DxC using the timed endpoint method, and lumbar spine BMD was measured by dual-energy X-ray absorptiometry (DXA). Multivariate linear regression models were used to explore the relationship between SUA and BMD by adjusting for age, race/Hispanic origin, drinking behavior, smoking behavior, physical activity, body mass index (BMI), poverty-to-income ratio (PIR), total protein, serum calcium, cholesterol, serum phosphorus, and blood urea nitrogen. After correcting for the above confounders, it was found that SUA was positively associated with lumbar spine BMD in the range of SUA < 5 mg/dL (ß = 0.006 95% CI 0.003-0.009, P < 0.001), and BMD of individuals in the highest quartile of SUA was 0.020 g/cm2 higher than those in the lowest quartile of SUA (ß = 0.020 95% CI 0.008-0.032, P = 0.003). This study showed that SUA was positively correlated with lumbar spine BMD in American men within a certain range. This gives clinicians some insight into how to monitor SUA levels to predict BMD levels during adolescence when bone is urgently needed for growth and development and during old age when bone loss is rapid.


Asunto(s)
Densidad Ósea , Ácido Úrico , Adolescente , Humanos , Masculino , Estados Unidos/epidemiología , Adulto Joven , Adulto , Persona de Mediana Edad , Encuestas Nutricionales , Absorciometría de Fotón , Huesos , Vértebras Lumbares/diagnóstico por imagen
18.
Macromol Biosci ; 24(1): e2200565, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36871156

RESUMEN

Tumor recurrence and wound microbial infection after tumor excision are serious threats to patients. Thus, the strategy to supply a sufficient and sustained release of cancer drugs and simultaneously engineer antibacterial properties and satisfactory mechanical strength is highly desired for tumor postsurgical treatment. Herein, A novel double-sensitive composite hydrogel embedded with tetrasulfide-bridged mesoporous silica (4S-MSNs) is developed. The incorporation of 4S-MSNs into oxidized dextran/chitosan hydrogel network, not only enhances the mechanical properties of hydrogels, but also can increase the specificity of drug with dual pH/redox sensitivity, thereby allowing more efficient and safer therapy. Besides, 4S-MSNs hydrogel preserves the favorable physicochemical properties of polysaccharide hydrogel, such as high hydrophilicity, satisfactory antibacterial activity, and excellent biocompatibility. Thus, the prepared 4S-MSNs hydrogel can be served as an efficient strategy for postsurgical bacterial infection and inhibition of tumor recurrence.


Asunto(s)
Quitosano , Nanopartículas , Humanos , Quitosano/farmacología , Quitosano/química , Hidrogeles/farmacología , Hidrogeles/química , Dextranos/farmacología , Dextranos/química , Dióxido de Silicio/química , Recurrencia Local de Neoplasia , Nanopartículas/química , Antibacterianos/farmacología
19.
Int Immunopharmacol ; 126: 111202, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-37988908

RESUMEN

OBJECTIVE: Gadd45ß have a regulatory role in cellular inflammation, proliferation and migration. However, the role of Gadd45ß in synovial inflammation in osteoarthritis (OA) remains to be explored. This study aimed to ascertain whether Gadd45ß is involved in OA synovial inflammation. METHODS: The rat model was induced by sodium iodoacetate and the cellular model was constructed with lipopolysaccharide (LPS)-induced fibroblast-like synoviocytes (FLSs). siRNA was applied to interfere with the expression of intracellular Gadd45ß. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of Gadd45ß mRNA and protein. The inflammation, proliferation, and migration of OA-FLSs were detected by enzyme-linked immunosorbent assay, cell scratch assay, 5-ethynyl-2'-deoxyuridine assay, etc. The effect of downregulation of Gadd45ß on the nuclear factor-κB (NF-κB) pathway was investigated. RESULTS: Expression of Gadd45ß in OA rat synovial tissues and OA-FLSs was increased, and LPS treatment promoted cell proliferation and enhanced cell migration. Gadd45ß interference inhibited the inflammation, proliferation and migration of cells induced by LPS. LPS promoted P65 expression in the nucleus and activated the NF-κB signaling pathway, whereas si-Gadd45ß reversed this situation. CONCLUSIONS: si-Gadd45ß inhibited the inflammatory response, proliferation and migration of FLSs, and activation of the NF-κB signaling pathway, which could delay the progression of OA. Hence, it may become a potential therapeutic target for OA.


Asunto(s)
Osteoartritis , Sinoviocitos , Animales , Ratas , Proliferación Celular , Células Cultivadas , Regulación hacia Abajo , Fibroblastos , Inflamación/metabolismo , Lipopolisacáridos/farmacología , FN-kappa B/metabolismo , Osteoartritis/metabolismo
20.
J Microbiol Immunol Infect ; 57(1): 118-127, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37963801

RESUMEN

BACKGROUND/PURPOSE: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is capable of causing serious community and hospital-acquired infections. However, currently, the identification of CRKP is complex and inefficient. Hence, this study aimed to develop methods for the early and effective identification of CRKP to allow reasonable antimicrobial therapy in a timely manner. METHODS: K. pneumoniae (KP)-, K. pneumoniae carbapenemase (KPC)- and New Delhi metallo-ß-lactamase (NDM)- specific CRISPR RNAs (crRNAs), polymerase chain reaction (PCR) primers and recombinase-aided amplification (RAA) primers were designed and screened in conserved sequence regions. We established fluorescence and lateral flow strip assays based on CRISPR/Cas13a combined with PCR and RAA, respectively, to assist in the detection of CRKP. Sixty-one clinical strains (including 51 CRKP strains and 10 carbapenem-sensitive strains) were collected for clinical validation. RESULTS: Using the PCR-CRISPR assay, the limit of detection (LOD) for KP and the blaKPC and blaNDM genes reached 1 copy/µL with the fluorescence signal readout. Using the RAA-CRISPR assay, the LOD could reach 101 copies/µL with both the fluorescence signal readout and the lateral flow strip readout. Additionally, the positivity rates of CRKP-positive samples detected by the PCR/RAA-CRISPR fluorescence and RAA-CRISPR lateral flow strip methods was 92.16% (47/51). The sensitivity and specificity reached 100% for KP and blaKPC and blaNDM gene detection. For detection in a simulated environmental sample, 1 CFU/cm2 KP could be detected. CONCLUSION: We established PCR/RAA-CRISPR assays for the detection of blaKPC and blaNDM carbapenemase genes, as well as KP, to facilitate the detection of CRKP.


Asunto(s)
Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Klebsiella , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Sistemas CRISPR-Cas , Pruebas de Sensibilidad Microbiana , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Infecciones por Klebsiella/tratamiento farmacológico
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA