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1.
Transplant Proc ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39242312

RESUMEN

OBJECTIVES: Ferroptosis plays a pivotal role in the pathogenesis of renal ischemia-reperfusion injury, where the processes are mediated by free ferrous ions and mitochondrial-released reactive oxygen species. However, the administration of high doses of cyclosporine A (CsA) or deferoxamine (DFO) poses a significant risk of renotoxicity. In contrast, low doses of DFO act as a ferrous iron chelator, and CsA functions as a mitochondrial reactive oxygen species blocker. This study aims to explore the potential protective effects of donor treatment with low-dose CsA, DFO, or their combination against ischemia-reperfusion injury during renal transplantation in a rat model. MATERIALS AND METHODS: In an ex vivo cold storage (CS) model utilizing renal slices, the impact of incorporating DFO, CsA, and a combination of both into the University of Wisconsin solution was assessed through the measurement of lactate dehydrogenase leakage. Additionally, their potential benefits were investigated in a rat donation after circulatory death (DCD) kidney transplant model, where the extent of damage was evaluated based on graft function, tubular necrosis, and inflammation. RESULTS: The co-administration of DFO and CsA effectively decreased the release of lactate dehydrogenase induced by CS ( P ≥ .05). In the in vivo model, this combined supplementation demonstrated a mitigating effect on reperfusion injury, evidenced by lower blood urea nitrogen levels and acute tubular necrosis scores compared to the control group (allP ≤ .05). Furthermore, the combined treatment significantly reduced apoptotic levels compared to the control group (P ≥ .05). CONCLUSIONS: The combined treatment with DFO and CsA mitigated the cold ischemia-reperfusion injury in the DCD kidney. Hence, this presents a new strategy for the CS of DCD kidney in clinical transplants.

2.
Cytokine ; 183: 156750, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39243567

RESUMEN

Insulin-like growth factors (IGFs) are crucial for embryonic and postnatal growth and development, influencing cell survival, metabolism, myogenesis, and cancer progression. Many studies have demonstrated that IGFs also play prominent roles in the modulation of both innate and adaptive immune systems during inflammation. Strikingly, IGFs dictate the phenotype and functional properties of macrophages and T cells. Furthermore, the interplay between IGFs and inflammatory cytokines may generate tissue-protective properties during inflammation. Herein, we review the recent advances on the dialogue between immune cells and IGFs, especially zooming in on the significance of immunomodulatory properties in inflammatory conditions, cancer and autoimmune diseases. The investigation of IGFs may have broad clinical implications.

3.
Small ; : e2403165, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39246173

RESUMEN

The development of small molecule photosensitizers based on iridium complex is limited by the mismatch between therapeutic effect and systemic toxicity, as well as the incomplete understanding of the molecular mechanism underlying cell death induction. Herein, a small molecule iridium complex IrC with high photocytotoxicity is synthesized, with half maximal inhibitory concentration as low as 91 nm, demonstrating excellent anti-tumor, relief of splenomegaly, and negligible side effects. Starting from the factors of effective photosensitizers, the in-depth theoretical analysis on photon absorption efficiency, energy transfer level matching, and properties of the triplet excited state of IrC is conducted. This also elucidates the feasibility of generating the high singlet oxygen quantum yield. In addition, the death mechanism induced by IrC is focused, innovatively utilizing GPX4-overexpression and GPX4-knockout cells via CRISPR/Cas9 technique to comprehensively verify ferroptosis and its further molecular mechanism. The generation of ROS mediated by IrC, along with the direct inhibition of GPX4 and glutathione, synergistically increased cellular oxidative stress and the level of lipid peroxidation. This study provides an effective approach for small molecule complexes to induce GPX4-dependent ferroptosis at low-dose photodynamic therapy.

4.
Aging (Albany NY) ; 162024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39237304

RESUMEN

Anti-inflammatory and antioxidant effects play crucial roles in the recovery of benign prostatic hyperplasia (BPH). Wenshenqianlie (WSQL) capsule, a typical traditional Chinese medicine formulation combining 14 Chinese herbs, has been reported to exert tonic effects on the kidneys and improve clinical symptoms of BPH. However, its potential antioxidative and anti-inflammatory properties and effects on the improvement of hormone levels have not been reported in depth. In this study, mice were subcutaneously injected with TP (5 mg/kg·d-1) to induce BPH. Forty-eight adult BALB/c male mice were randomly allocated to six groups based on the type of drug administered by gavage: control, BPH, BPH+WSQL (40 and 80 mg/kg·d-1), BPH+finasteride (1 mg/kg·d-1), and WSQL-only treated (80 mg/kg·d-1). We investigated the anti-inflammatory and antioxidant effect and mechanism of WSQL on BPH via histopathological examination, immunohistochemistry, enzyme-linked immunosorbent assay, and western blotting combined with in vivo serum metabolomics, gut microbiomics analysis. WSQL alleviated prostate hyperplasia and reduced prostate-specific antigen, dihydrotestosterone, testosterone, and inflammation levels. Gut microbiomics and serum non-targeted metabolomics determined that the protective effect of WSQL against BPH may be related to the improvement of inflammation and testosterone-related gut microbiota and serum metabolites. Further studies showed that WSQL ameliorated nuclear factor-kappa B, its downstream inflammatory factors, and nuclear factor E2-related factor 2 pathway.

6.
Ann Hematol ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39227450

RESUMEN

The superiority and tolerability of daratumumab plus bortezomib/melphalan/prednisone (D-VMP) versus bortezomib/melphalan/prednisone (VMP) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) was previously described in the global phase 3 ALCYONE study. The primary analysis of the phase 3 OCTANS study further demonstrated the superiority and tolerability of D-VMP (n = 144) versus VMP (n = 71) in transplant-ineligible Asian patients with NDMM. The current analysis describes the final efficacy and safety outcomes for D-VMP versus VMP in OCTANS, with a follow-up of > 3 years. D-VMP demonstrated a benefit versus VMP with regard to the rate of very good partial response or better (80.1% vs. 47.3%), median progression-free survival (38.7 vs. 19.2 months), median time to next treatment (46.8 vs. 20.6 months), rate of complete response or better (46.6% vs. 18.9%), median duration of response (41.3 vs. 18.5 months), achievement of minimal residual disease (MRD) negativity (40.4% vs. 10.8%), and sustained MRD negativity for ≥ 12 months (24.7% vs. 1.4%) and ≥ 18 months (15.1% vs. 1.4%). Median progression-free survival was longer among patients who achieved MRD negativity and sustained MRD negativity. The progression-free survival benefit observed with D-VMP was preserved across most clinically relevant subgroups, including patients with high-risk cytogenetics. No new safety concerns were identified with extended follow-up. This final analysis of OCTANS continues to demonstrate a clinical benefit for D-VMP versus VMP in transplant-ineligible Asian patients with NDMM, consistent with the global ALCYONE study, and supports the use of daratumumab combinations in this population. Trial registration: ClinicalTrials.gov Identifier NCT03217812 submitted July 13, 2017.

7.
Stress Biol ; 4(1): 39, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39276279

RESUMEN

To assess the effects of a time-restricted feeding (TRF) regimen on meat quality of pigs exposed to high ambient temperature, a two-month feeding and heat treatment (HT) trial was conducted using a 2 × 2 factorial design. A total of 24 growing pigs (11.0 ± 1.9 kg) were randomly divided into four groups: thermal neutral group (NT, 24 ± 3 °C), HT group (exposed to a high temperature at 35 ± 2 °C from 11:00 to 15:00), TRF group and HT + TRF group (HT and TRF co-treatment group, n = 6 for each group). Pigs in TRF groups got access to feed within 5 h from 9:00 to14:00, while the others were fed at 6:00, 11:30, and 16:00. All pigs received the same diet during the trail. The results showed that HT increased the drip loss, shear force, lightness, and malondialdehyde production in Longissimus thoracis et lumborum (LTL) muscle. TRF reversely reduced the shear force and drip loss, accompanied by decreased intramuscular fat and increased moisture content. Enhanced fiber transformation from type 1 to type 2b and down-regulated expression of muscle growth-related genes were observed by HT, while TRF suppressed the fiber transformation and expression of muscle atrophy-related genes. Furthermore, TRF restored the diminished protein expressions of Nrf2 and HO-1 in LTL muscle by chronic HT. Accumulation of HSP70 in muscle of HT group was reduced by treatment of TRF. HT declined the expression of vital genes involved in fatty acids poly-desaturation and the proportion of (polyunsaturated fatty acids) PUFAs, mainly omega-6 in LTL muscle, while TRF group promoted the expression of poly-desaturation pathway and displayed the highest proportion of PUFAs. These results demonstrated that TRF relieved the chronic high temperature affected meat quality by the restored expression of Nrf2/HO-1 anti-oxidative cascade, modified muscle fiber composition, and enriched PUFAs in LTL muscle.

8.
Front Endocrinol (Lausanne) ; 15: 1439351, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39279997

RESUMEN

Background: Endogenous insulin supplementation is essential for individuals with type 1 diabetes (T1D). However, current treatments, including pancreas transplantation, insulin injections, and oral medications, have significant limitations. The development of engineered cells that can secrete endogenous insulin offers a promising new therapeutic strategy for type 1 diabetes (T1D). This approach could potentially circumvent autoimmune responses associated with the transplantation of differentiated ß-cells or systemic delivery of viral vectors. Methods: We utilized CRISPR/Cas9 gene editing coupled with homology-directed repair (HDR) to precisely integrate a promoter-free EMCVIRES-insulin cassette into the 3' untranslated region (UTR) of the GAPDH gene in human HEK-293T cells. Subsequently quantified insulin expression levels in these engineered cells, the viability and functionality of the engineered cells when seeded on different cell vectors (GelMA and Cytopore I) were also assessed. Finally, we investigated the therapeutic potential of EMCVIRES-based insulin secretion circuits in reversing Hyperglycaemia in T1D mice. Result: Our results demonstrate that HDR-mediated gene editing successfully integrated the IRES-insulin loop into the genome of HEK-293T cells, a non-endocrine cell line, enabling the expression of human-derived insulin. Furthermore, Cytopore I microcarriers facilitated cell attachment and proliferation during in vitro culture and enhanced cell survival post-transplantation. Transplantation of these cell-laden microcarriers into mice led to the development of a stable, fat-encapsulated structure. This structure exhibited the expression of the platelet-endothelial cell adhesion molecule CD31, and no significant immune rejection was observed throughout the experiment. Diabetic mice that received the cell carriers reversed hyperglycemia, and blood glucose fluctuations under simulated feeding stimuli were very similar to those of healthy mice. Conclusion: In summary, our study demonstrates that Cytopore I microcarriers are biocompatible and promote long-term cell survival in vivo. The promoter-free EMCVIRES-insulin loop enables non-endocrine cells to secrete mature insulin, leading to a rapid reduction in glucose levels. We have presented a novel promoter-free genetic engineering strategy for insulin secretion and proposed an efficient cell transplantation method. Our findings suggest the potential to expand the range of cell sources available for the treatment of diabetes, offering new avenues for therapeutic interventions.


Asunto(s)
Diabetes Mellitus Tipo 1 , Edición Génica , Hiperglucemia , Células Secretoras de Insulina , Insulina , Humanos , Animales , Hiperglucemia/terapia , Hiperglucemia/metabolismo , Ratones , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Insulina/genética , Células HEK293 , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/genética , Edición Génica/métodos , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/genética , Sitios Internos de Entrada al Ribosoma/genética , Regiones Promotoras Genéticas , Sistemas CRISPR-Cas
9.
Nat Commun ; 15(1): 7654, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39227578

RESUMEN

Citrullination plays an essential role in various physiological or pathological processes, however, whether citrullination is involved in regulating tumour progression and the potential therapeutic significance have not been well explored. Here, we find that peptidyl arginine deiminase 4 (PADI4) directly interacts with and citrullinates hypoxia-inducible factor 1α (HIF-1α) at R698, promoting HIF-1α stabilization. Mechanistically, PADI4-mediated HIF-1αR698 citrullination blocks von Hippel-Lindau (VHL) binding, thereby antagonizing HIF-1α ubiquitination and subsequent proteasome degradation. We also show that citrullinated HIF-1αR698, HIF-1α and PADI4 are highly expressed in hepatocellular carcinoma (HCC) tumour tissues, suggesting a potential correlation between PADI4-mediated HIF-1αR698 citrullination and cancer development. Furthermore, we identify that dihydroergotamine mesylate (DHE) acts as an antagonist of PADI4, which ultimately suppresses tumour progression. Collectively, our results reveal citrullination as a posttranslational modification related to HIF-1α stability, and suggest that targeting PADI4-mediated HIF-1α citrullination is a promising therapeutic strategy for cancers with aberrant HIF-1α expression.


Asunto(s)
Carcinoma Hepatocelular , Citrulinación , Progresión de la Enfermedad , Subunidad alfa del Factor 1 Inducible por Hipoxia , Neoplasias Hepáticas , Arginina Deiminasa Proteína-Tipo 4 , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Arginina Deiminasa Proteína-Tipo 4/metabolismo , Animales , Línea Celular Tumoral , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Ubiquitinación , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismo , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Ratones , Células HEK293 , Estabilidad Proteica/efectos de los fármacos , Desiminasas de la Arginina Proteica/metabolismo , Desiminasas de la Arginina Proteica/genética , Ratones Desnudos , Masculino
11.
Int J Mol Sci ; 25(17)2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39273586

RESUMEN

A narrow genetic basis limits further the improvement of modern Gossypium hirsutum cultivar. The abundant genetic diversity of wild species provides available resources to solve this dilemma. In the present study, a chromosome segment substitution line (CSSL) population including 553 individuals was established using G. darwinii accession 5-7 as the donor parent and G. hirsutum cultivar CCRI35 as the recipient parent. After constructing a high-density genetic map with the BC1 population, the genotype and phenotype of the CSSL population were investigated. A total of 235 QTLs, including 104 QTLs for fiber-related traits and 132 QTLs for seed-related traits, were identified from four environments. Among these QTLs, twenty-seven QTLs were identified in two or more environments, and twenty-five QTL clusters consisted of 114 QTLs. Moreover, we identified three candidate genes for three stable QTLs, including GH_A01G1096 (ARF5) and GH_A10G0141 (PDF2) for lint percentage, and GH_D01G0047 (KCS4) for seed index or oil content. These results pave way for understanding the molecular regulatory mechanism of fiber and seed development and would provide valuable information for marker-assisted genetic improvement in cotton.


Asunto(s)
Mapeo Cromosómico , Cromosomas de las Plantas , Fibra de Algodón , Gossypium , Fenotipo , Sitios de Carácter Cuantitativo , Semillas , Gossypium/genética , Semillas/genética , Mapeo Cromosómico/métodos , Cromosomas de las Plantas/genética , Fitomejoramiento/métodos , Genotipo
12.
Plants (Basel) ; 13(17)2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39274011

RESUMEN

Salt stress can affect various physiological processes in plants, ultimately hindering their growth and development. Melatonin (MT) can effectively resist multiple abiotic stresses, improving plant stress resistance. To analyze the mechanism of exogenous MT to enhance salt tolerance in red clover, we conducted a comprehensive study to examine the influence of exogenous MT on various parameters, including seed germination indices, seedling morphological traits, and physiological and photosynthetic indicators, using four distinct red clover varieties (H1, H2, H3, and H4). This investigation was performed under various salt stress conditions with differing pH values, specifically utilizing NaCl, Na2SO4, NaHCO3, and Na2CO3 as the salt stressors. The results showed that MT solution immersion significantly improved the germination indicators of red clover seeds under salt stress. The foliar spraying of 50 µM and 25 µM MT solution significantly increased SOD activity (21-127%), POD activity, soluble sugar content, proline content (22-117%), chlorophyll content (2-66%), and the net photosynthetic rate. It reduced the MDA content (14-55%) and intercellular CO2 concentration of red clover seedlings under salt stress. Gray correlation analysis and the Mantel test further verified that MT is a key factor in enhancing seed germination and seedling growth of red clover under salt stress; the most significant improvement was observed for NaHCO3 stress. MT is demonstrated to improve the salt tolerance of red clover through a variety of mechanisms, including an increase in antioxidant enzyme activity, osmoregulation ability, and cell membrane stability. Additionally, it improves photosynthetic efficiency and plant architecture, promoting energy production, growth, and optimal resource allocation. These mechanisms function synergistically, enabling red clover to sustain normal growth and development under salt stress.

13.
Plant Commun ; : 101130, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39257006

RESUMEN

Cotton, an intriguing plant species shaped by polyploidization, evolution, and domestication, holds particular interest due to the complex mechanisms governing fiber traits across its two subgenomes. However, the regulatory elements or transcriptional networks between subgenomes during fiber elongation remain elusive. Here, we analyzed 1,462 cotton fiber samples to reconstruct gene expression regulatory networks influencing fiber cell elongation. Inter-subgenomic eQTLs largely dictate gene transcription, with a notable tendency for the D subgenome to regulate A subgenome eGenes. This regulation showcases synchronized homoeologous gene expression driven by colocalized eQTLs and divergent patterns that diminish genetic correlations, thus leading to preferential expression in the A and D subgenomes. Hotspot456 emerged as a key regulator of fiber initiation and elongation, and artificial selection of trans-eQTLs in hotspot456 positively regulating KCS1 has facilitated cell elongation. To elucidate the roles of trans-eQTL in improved fiber breeding, experimentation confirmed the inhibition of GhTOL9 by a specific trans-eQTL via GhWRKY28, which negatively impacts fiber elongation. We propose a model where the GhWRKY28-GhTOL9 module, through the Endosomal Sorting Complex Required for Transport pathway, regulates this process. This research significantly advances our understanding of cotton's evolutionary, domestication processes, and the intricate regulatory mechanisms underlying significant plant traits.

14.
J Extracell Vesicles ; 13(9): e12505, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39235072

RESUMEN

Reactive oxygen species (ROS)-induced oxidative DNA damages have been considered the main cause of mutations in genes, which are highly related to carcinogenesis and tumour progression. Extracellular vesicles play an important role in cancer metastasis. However, the precise role of DNA oxidative damage in extracellular vesicles (EVs)-mediated cancer cell migration and invasion remains unclear. Here, we reveal that ROS-mediated DNA oxidative damage signalling promotes tumour metastasis through increasing EVs release. Mechanistically, 8-oxoguanine DNA glycosylase (OGG1) recognises and binds to its substrate 8-oxo-7,8-dihydroguanine (8-oxoG), recruiting NF-κB to the synaptotagmin 7 (SYT7) promoter and thereby triggering SYT7 transcription. The upregulation of SYT7 expression leads to increased release of E-cadherin-loaded EVs, which depletes intracellular E-cadherin, thereby inducing epithelial-mesenchymal transition (EMT). Notably, Th5487, the inhibitor of DNA binding activity of OGG1, blocks the recognition and transmission of oxidative signals, alleviates SYT7 expression and suppresses EVs release, thereby preventing tumour progression in vitro and in vivo. Collectively, our study illuminates the significance of 8-oxoG/OGG1/SYT7 axis-driven EVs release in oxidative stress-induced tumour metastasis. These findings provide a deeper understanding of the molecular basis of cancer progression and offer potential avenues for therapeutic intervention.


Asunto(s)
ADN Glicosilasas , Vesículas Extracelulares , Metástasis de la Neoplasia , Animales , Femenino , Humanos , Ratones , Línea Celular Tumoral , Movimiento Celular , Daño del ADN , ADN Glicosilasas/metabolismo , Transición Epitelial-Mesenquimal , Vesículas Extracelulares/metabolismo , Guanina/análogos & derivados , Guanina/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal
15.
Front Public Health ; 12: 1421211, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39257951

RESUMEN

Objective: We investigated the risk factors associated with severe or critical Coronavirus disease 2019 (COVID-19) infection due to the Omicron variant in patients with myasthenia gravis (MG) and determined the potential effect of COVID-19 on myasthenic exacerbation during the Omicron pandemic. Methods: This retrospective study included 287 patients with MG in Tianjin, China. Clinical data of the patients were collected using electronic questionnaires, databases, and clinical records. Results: The overall infection rate was 84.7%. Advanced age, comorbidities, generalized phenotype, and MG instability were drivers of COVID-19 severity, and post-COVID-19 myasthenic exacerbation. The concurrent use of a steroid-sparing agent did not affect COVID-19 susceptibility or severity. It did lower the risk of myasthenic exacerbation after COVID-19 infection. Patients with severe COVID-19 experienced myasthenic exacerbation earlier than patients with non-severe infection (p < 0.001). The severity of COVID-19 (Hazards Ratio = 3.04, 95% CI: 1.41-6.54, p = 0.004) and the clinical phenotype (Hazards Ratio = 3.29, 95% CI: 1.63-6.63, p < 0.001) emerged as independent risk factors for early MG exacerbation. Conclusion: Generally, patients with MG appear to be susceptible to the Omicron strains. Immunotherapy for MG did not increase COVID-19 susceptibility or severity. We do not advocate an immediate cessation of ongoing immunosuppressive treatments once a COVID-19 infection is diagnosed. Instead, a judicious evaluation of the risks and benefits, tailored to each individual, is recommended.


Asunto(s)
COVID-19 , Miastenia Gravis , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/complicaciones , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Adulto , Factores de Riesgo , Anciano , Índice de Severidad de la Enfermedad , Comorbilidad
17.
J Pharm Biomed Anal ; 251: 116451, 2024 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-39217702

RESUMEN

The metabolic disorders in the purine degradation pathway have proven to be closely associated with several human diseases. However, the etiology is not yet fully understood. Profile assay of purine intermediates and uric acid involved in the metabolic pathway can provide additional insight into the nature and severity of related diseases. Purine metabolites are endogenous chemicals with high hydrophilicity, polarity, and similar structures, thus there is a great need for a specific method to quantify them directly in biological fluids with a short running time. Herein, eight purine degradation pathway metabolites, including xanthine, hypoxanthine, guanine, xanthosine, inosine, guanosine, adenosine and uric acid, in human plasma were quantitatively measured using hydrophilic interaction chromatography-tandem high-resolution mass spectrometry (HILIC-HRMS) in a short running time of 10 min. The method was systematically validated for specificity, linearity of the calibration curve, the limit of detection, the limit of quantification, the lower limit of quantification, precision, accuracy, extraction recovery, matrix effect, and stability. The results showed that the method was linear (R2 > 0.99), accurate (the intra- and inter-day recoveries of all analytes ranged from 90.0 % to 110.0 %), and precise (the intra- and inter-day precisions were less than 6.7 % and 8.9 %, respectively) with the lower limits of quantification ranging from 3 to 10,000 ng/mL. The extraction recoveries and matrix effects were repeatable and stable. All the analytes were stable in the autosampler and could be subject to three freeze-thaw cycles. The developed method was ultimately applied to 100 plasma specimens from healthy individuals. The results showed that the concentrations of different purine metabolites varied dramatically in plasma specimens. Diet and body mass index (BMI) were the most significant factors determining purine levels, followed by drinking and sex. Age, smoking and bedtime showed a very weak correlation with purine metabolism. The findings of the present work reveal the characteristics of purine metabolism in human plasma under non-pathological conditions. The results also highlight the factors that can cause changes in purine metabolism, which are useful in developing effective treatment strategies for metabolic disorders of purines, particularly for those caused by lifestyle factors.


Asunto(s)
Interacciones Hidrofóbicas e Hidrofílicas , Purinas , Espectrometría de Masas en Tándem , Humanos , Purinas/metabolismo , Purinas/sangre , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Reproducibilidad de los Resultados , Límite de Detección , Masculino , Calibración , Ácido Úrico/sangre , Adulto
18.
Ultrason Sonochem ; 110: 107056, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39232289

RESUMEN

Based on sonochemistry, green synthesis methods play an important role in the development of nanomaterials. In this work, a novel chitosan modified MnMoO4/g-C3N4 (MnMoO4/g-C3N4/CHIT) was developed using ultrasonic cell disruptor (500 W, 30 kHz) for ultra-sensitive electrochemical detection of tinidazole (TNZ) in the environment. The morphology and surface properties of the synthesized MnMoO4/g-C3N4/CHIT electrode were characterized using X-ray diffraction (XRD), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM) and transmission electron microscope (TEM). Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques were utilized to assess the electrochemical performance of TNZ. The results indicate that the electrochemical detection performance of TNZ is highly efficient, with a detection limit (LOD) of 3.78 nM, sensitivity of 1.320 µA·µM-1·cm-2, and a detection range of 0.1-200 µM. Additionally, the prepared electrode exhibits excellent selectivity, desirable anti-interference capability, and decent stability. MnMoO4/g-C3N4/CHIT can be successfully employed to detect TNZ in both the Songhua River and tap water, achieving good recovery rates within the range of 93.0 % to 106.6 %. Consequently, MnMoO4/g-C3N4/CHIT's simple synthesis might provide a new electrode for the sensitive, repeatable, and selective measurement of TNZ in real-time applications. Using the MnMoO4/g-C3N4/CHIT electrode can effectively monitor and detect the concentration of TNZ in environmental water, guiding the sewage treatment process and reducing the pollution level of antibiotics in the water environment.

19.
Angiology ; : 33197241280527, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259527

RESUMEN

We investigated the effect of sex and age on the association between serum creatinine/cystatin C (CCR) ratio and carotid plaque in patients with type 2 diabetes mellitus (T2DM). The carotid plaque group and the non-plaque group were divided according to cervical vascular ultrasound; the general and biochemical data of the two groups were compared according to CCR, gender, and age. Binary logistic regression was used to analyze the factors influencing carotid plaque. A total of 1429 patients with T2DM were included in this study. On multivariate analysis, CCR was an independent predictor of carotid plaque with an adjusted odds ratio (OR) of 1.681 [1.250-2.260]. The risk of carotid plaque in men with T2DM increased significantly (P < .05) with decreasing levels of CCR. In addition, an association between CCR and carotid plaque was found in individuals with T2DM <65 years of age (P < .05). CCR is strongly associated with the risk of carotid plaques in persons with T2DM and are an independent risk factor for carotid plaques in men and people aged <65 years with T2DM.

20.
Food Chem X ; 23: 101727, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39253012

RESUMEN

Antarctic krill oil (KO) is known for its poor oxidative stability, especially in emulsion systems. In this experiment, a complex of scallop water-soluble protein-resveratrol (SWPs-RES) was mixed with KO to create high internal phase emulsions (HIPEs) with varying RES ratios. The addition of RES led to noticeable conformational changes in SWPs, including fluorescence bursts, alterations in secondary structure, and modifications in binding motifs. The SWPs-RES complex (1:0.2) demonstrated the most effective free radical scavenging activities (HO: 38.61%, DPPH: 72.49%, ABTS: 85.66%), while the SWPs-RES complex (1:0.025) exhibited the highest emulsifying capacity. Furthermore, HIPEs containing the SWPs-RES complex (1:0.2) displayed improved rheological properties, physical stability, and enhanced oxidative stability against lipid oxidation during storage and simulated in vitro digestion. This study lays a scientific foundation for the utilization of scallop protein and Antarctic krill oil in the food industry.

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