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1.
Artículo en Inglés | MEDLINE | ID: mdl-39322981

RESUMEN

Nanozymes have been developed to overcome the inherent limitations of natural enzymes, such as their low stability and high cost. However, their efficacy has been hindered by their relatively low specificity and activity. Here, we demonstrate the self-assembly of individual copper nanoclusters (CuNCs) via a simple yet fast (10 min) DNA nanosheet (DNS)-templated method, enhancing the peroxidase-like activity and specificity of CuNCs. Furthermore, we demonstrate the successful assembly of CuNCs on different DNA nanostructures by atomic force microscopy (AFM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The resulting micron-scale ultrathin DNA nanosheet-templated CuNCs (DNS@CuNCs) exhibit exceptional catalytic activity, with a specific activity reaching 1.79 × 103 U mg-1. Investigation into the catalytic process reveals that the enhanced activity and specificity arise from disparities in active intermediate content before and after CuNCs assembly. Significantly, the DNS@CuNCs-based biosensor demonstrates remarkable anti-interference capabilities, enabling the detection of H2O2 in undiluted human serum for the first time with a detection limit of 0.99 µM.

2.
Sci Rep ; 14(1): 22064, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39333312

RESUMEN

Protein Disulfide-Isomerase A2 (PDIA2) is a gene that encodes proteins, responsible for protein folding and modification within cells. The development and course of many disorders are intimately linked to the aberrant expression of PDIA2. Nevertheless, more research is necessary to fully understand PDIA2's biological significance in pan-cancer, notably in prostate cancer (PCa). PDIA2 expression is elevated in various tumors and closely related to patient prognosis. Patients with prostate cancer who express PDIA2 high in particular have a bad prognosis in terms of progression-free survival. In addition, the upregulation of PDIA2 expression in prostate cancer patients is accompanied by higher Gleason scores, advanced tumor staging, lymph node metastasis, and elevated PSA levels. Detailed experiments further demonstrate that PDIA2 is a carcinogenic gene affecting prostate cancer cells' response to dasatinib therapy. For patients with prostate cancer, there is a clear positive connection between the expression level of PDIA2 and a bad prognosis. The prostate cancer treatment efficacy of dasatinib is hampered by PDIA2, which is intimately linked to the growth, invasion, and metastasis of PCa cells. In summary, our research highlights the potential of PDIA2 as a biomarker for the diagnosis and management of PCa.


Asunto(s)
Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Próstata , Proteína Disulfuro Isomerasas , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Proteína Disulfuro Isomerasas/metabolismo , Proteína Disulfuro Isomerasas/genética , Pronóstico , Línea Celular Tumoral , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Regulación hacia Abajo
3.
Heliyon ; 10(17): e36926, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39296084

RESUMEN

Fluorescent brightening agent OB-1 (OB-1) is often used in plastic goods because of its non-toxic nature, chemical stability, remarkable heat resistance, and light stability. Raw OB-1 is challenging to use in textiles using the exhaustion method. This study used a novel method using raw OB-1 powder to whiten polyester fabric in water and decamethylcyclopentasiloxane (D5). The Taguchi approach investigated the interaction between whitening process parameters such as temperature, OB-1 mass, water: D5 ratio, and treatment time with four levels. The study shows that the temperature and water: D5 ratio during the whitening process significantly affect the whiteness of polyester fabric (P < 0.05), with contribution percentages of 74.2 % and 25.2 %. Subsequently, various analytical techniques were employed, including FTIR, SEM, TGA, and XRD, to characterise the whitened fabric. The findings imply that using water: D5 medium was effective in whitening polyester fabric without causing major alterations to the structure of the PET fabric. The study also examined the fastness of washing and crocking to determine their whitening stability. Overall, polyester fabric whitened with water and D5 medium exhibited satisfactory whitening performance and might be a potential scope for use on a larger scale in developing the sustainable textile industry.

4.
J Cell Mol Med ; 28(17): e70035, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39245790

RESUMEN

Diabetes-related bone loss represents a significant complication that persistently jeopardizes the bone health of individuals with diabetes. Primary cilia proteins have been reported to play a vital role in regulating osteoblast differentiation in diabetes-related bone loss. However, the specific contribution of KIAA0753, a primary cilia protein, in bone loss induced by diabetes remains unclear. In this investigation, we elucidated the pivotal role of KIAA0753 as a promoter of osteoblast differentiation in diabetes. RNA sequencing demonstrated a marked downregulation of KIAA0753 expression in pro-bone MC3T3 cells exposed to a high glucose environment. Diabetes mouse models further validated the downregulation of KIAA0753 protein in the femur. Diabetes was observed to inhibit osteoblast differentiation in vitro, evidenced by downregulating the protein expression of OCN, OPN and ALP, decreasing primary cilia biosynthesis, and suppressing the Hedgehog signalling pathway. Knocking down KIAA0753 using shRNA methods was found to shorten primary cilia. Conversely, overexpression KIAA0753 rescued these changes. Additional insights indicated that KIAA0753 effectively restored osteoblast differentiation by directly interacting with SHH, OCN and Gli2, thereby activating the Hedgehog signalling pathway and mitigating the ubiquitination of Gli2 in diabetes. In summary, we report a negative regulatory relationship between KIAA0753 and diabetes-related bone loss. The clarification of KIAA0753's role offers valuable insights into the intricate mechanisms underlying diabetic bone complications.


Asunto(s)
Diferenciación Celular , Proteínas Asociadas a Microtúbulos , Osteoblastos , Transducción de Señal , Animales , Humanos , Masculino , Ratones , Línea Celular , Cilios/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/genética , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Ratones Endogámicos C57BL , Osteoblastos/metabolismo , Osteogénesis/genética , Proteínas Asociadas a Microtúbulos/metabolismo
5.
Int J Biol Sci ; 20(11): 4424-4437, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39247809

RESUMEN

Prostate cancer presents as an immunologically "cold" malignancy, characterized by a lack of response to immunotherapy in the majority of patients. The dysfunction of prostate tumor metabolism is recognized as a critical factor in immune evasion, resulting in reduced effectiveness of immunotherapeutic interventions. Despite this awareness, the precise molecular mechanisms underpinning metabolic dysregulation in prostate cancer and its intricate relationship with immune evasion remain incompletely elucidated. In this study, we introduce the multi-drug resistance protein ABCC4/MRP4 as a key player prominently expressed in prostate cancer, exerting a pivotal role in suppressing the activity of intratumoral CD8+ T cells. Depletion of ABCC4 in prostate cancer cells halts the release of prostaglandin E2 (PGE2), a molecule that diminishes the population of CD8+ T cells and curtails their cytotoxic capabilities. Conversely, constraining the activation of PGE2 signaling in CD8+ T cells effectively improved the efficacy of prostate cancer treatment with PD-1 blockade. During this process, downregulation of the JAK1-STAT3 pathway and depolarization of mitochondria emerge as crucial factors contributing to T cell anergy. Collectively, our research identifies the ABCC4-PGE2 axis as a promising target for reversing dysfunction within tumor-infiltrating lymphocytes (TILs) and augmenting the suboptimal responsiveness to immunotherapy in prostate cancer.


Asunto(s)
Linfocitos T CD8-positivos , Dinoprostona , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Neoplasias de la Próstata , Masculino , Neoplasias de la Próstata/metabolismo , Linfocitos T CD8-positivos/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Dinoprostona/metabolismo , Humanos , Receptor de Muerte Celular Programada 1/metabolismo , Línea Celular Tumoral , Animales , Ratones
6.
Interdiscip Sci ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39230797

RESUMEN

BACKGROUND: Accurate identification of cancer subtypes is crucial for disease prognosis evaluation and personalized patient management. Recent advances in computational methods have demonstrated that multi-omics data provides valuable insights into tumor molecular subtyping. However, the high dimensionality and small sample size of the data may result in ambiguous and overlapping cancer subtypes during clustering. In this study, we propose a novel contrastive-learning-based approach to address this issue. The proposed end-to-end deep learning method can extract crucial information from the multi-omics features by self-supervised learning for patient clustering. RESULTS: By applying our method to nine public cancer datasets, we have demonstrated superior performance compared to existing methods in separating patients with different survival outcomes (p < 0.05). To further evaluate the impact of various omics data on cancer survival, we developed an XGBoost classification model and found that mRNA had the highest importance score, followed by DNA methylation and miRNA. In the presented case study, our method successfully clustered subtypes and identified 14 cancer-related genes, of which 12 (85.7%) were validated through literature review. CONCLUSIONS: Our findings demonstrate that our method is capable of identifying cancer subtypes that are both statistically and biologically significant. The code about COLCS is given at: https://github.com/Mercuriiio/COLCS .

7.
Sci Rep ; 14(1): 21049, 2024 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251810

RESUMEN

Multiple investigations have demonstrated the crucial involvement of T-cell exhaustion (TEX) in anti-tumor immune response and their strong correlation with prognosis. This study aimed at creating a strong signature using TEX for gastric cancer through bioinformatics analysis and experimental validation. We utilized data from The Cancer Genome Atlas (TCGA) databases to retrieve RNA-seq data from patients with stomach adenocarcinoma (STAD). Genes related to TEX were discovered using gene set variance analysis (GSVA) and weighted gene correlation network analysis (WGCNA). Subsequently, prognostic signature based on TEX was developed using LASSO-Cox analysis. Relationship between key genes and immune cells were examined. Finally, biological function of a key TEX-related gene PTPRT in gastric cancer was verified by in vivo experiment. A total of 29 TEX-related biomarkers were screened by WGCNA and random forest. Among them, five core signatures (PTPRT, CAV2, PPIH, PRDM2, and FGF1), further identified by LASSO-Cox, were considered as strong predictors of prognosis for gastric cancer and associated with immune infiltration. PTPRT gene had the largest number of SNPs, with the most mutation types. In vivo experiments revealed that PTPRT overexpression significantly inhibited tumor malignant progression and accelerated apoptosis through stimulating the secretion of killer cytokines such as TNF-α and IFN-γ. In addition, flow cytometry revealed that PTPRT overexpression alleviated TEX by increasing the abundance of CD8+ T cells, with inhibition of cell surface PD-1 and Tim-3. The predictive prognostic value of TEX gene expression levels was evaluated in patients with gastric cancer, providing a new perspective for precision immuno-oncology studies.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Gástricas , Neoplasias Gástricas/genética , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/patología , Neoplasias Gástricas/diagnóstico , Humanos , Biomarcadores de Tumor/genética , Pronóstico , Regulación Neoplásica de la Expresión Génica , Animales , Linfocitos T/inmunología , Linfocitos T/metabolismo , Ratones , Masculino , Biología Computacional/métodos , Femenino , Perfilación de la Expresión Génica , Agotamiento de Células T
8.
Foods ; 13(17)2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39272418

RESUMEN

Scented green tea (Camellia sinensis) is a type of reprocessed green tea produced by scenting with flowers. To investigate the differences in the volatiles of scented green tea processed with four different flowers (Jasminum sambac, Osmanthus fragrans, Michelia alba, and Rosa rugosa), gas chromatography-ion mobility spectrometry (GC-IMS) and gas chromatography-mass spectrometry (GC-MS) were employed to detect and identify the volatile compounds in the four types of scented teas. GC-IMS and GC-MS identified 108 and 101 volatile compounds, respectively. The key characteristic volatile compounds, namely indole, linalool, ß-myrcene, benzyl acetate, and ethyl benzoate (jasmine tea); cedrol, (E)-ß-ionone, γ-decalactone, and dihydro-ß-ionol (osmanthus tea); geraniol, phenylethyl alcohol, jasmone, methyl jasmonate, hexadecanoic acid, 4-ethyl-benzaldehyde, 2-methylbutyl hexanoate, and indole (michelia tea); and 3,5-dimethoxytoluene, (E)-ß-ionone, and 2-methylbutyl hexanoate (rose tea), were identified through chemometric analysis combined with relative odor activity values (ROAVs) and sensory evaluation. This study provides new insights into the formation of aroma molecular fingerprints during green tea scenting with flowers, providing theoretical guidance for infusing distinct aroma characteristics into green tea during scented tea processing.

9.
MedComm (2020) ; 5(10): e713, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39290253

RESUMEN

Magnesium imbalances commonly exist in septic patients. However, the association of serum magnesium levels with mortality in septic patients remains uncertain. Herein, we elucidated the association between serum magnesium and all-cause mortality in septic patients from American and Chinese cohorts by analyzing data from 9099 patients in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and 1727 patients from a university-affiliated hospital' intensive care unit in China. Patients in both cohorts were categorized into five groups based on serum magnesium quintiles from the MIMIC-IV dataset. Patients with higher serum magnesium levels exhibited an increased risk of 28-day mortality in both cohorts. The restricted cubic spline (RCS) curves revealed a progressively elevated risk of 28-day mortality with increasing serum magnesium in MIMIC-IV cohort, while a J-shaped correlation was observed in institutional cohort. Our findings have validated the association between high serum magnesium and high mortality in sepsis across different races and medical conditions. Serum magnesium levels might be useful in identifying septic patients at higher mortality risk.

11.
Chem Rec ; 24(9): e202400085, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39148161

RESUMEN

Rechargeable aluminum ion batteries (AIBs) have recently gained widespread research concern as energy storage technologies because of their advantages of being safe, economical, environmentally friendly, sustainable, and displaying high performance. Nevertheless, the intense Coulombic interactions between the Al3+ ions with high charge density and the lattice of the electrode body lead to poor cathode kinetics and limited cycle life in AIBs. This paper reviews the recent advances in the cathode design of AIBs to gain a comprehensive understanding of the opportunities and challenges presented by current AIBs. In addition, the advantages, limitations, and possible solutions of each cathode material are discussed. Finally, the future development prospect of the cathode materials is presented.

12.
Transl Androl Urol ; 13(7): 1219-1227, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39100834

RESUMEN

Background: Multiparametric magnetic resonance imaging (mpMRI) is a commonly used method to diagnose pelvic lymph node metastasis (PLNM) in prostate cancer (PCa) patients, but there are few comparative studies on mpMRI and 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) in locally advanced PCa (LAPC) patients. Therefore, we designed a retrospective study to compare the diagnostic value of 68Ga-PSMA PET/CT and mpMRI for PLNM of LAPC. Methods: A retrospective study was performed on 50 patients with LAPC who underwent radical prostatectomy (RP) in Tongji Hospital from 2021 to 2023. All patients underwent PET/CT and mpMRI examination, and were diagnosed as LAPC before surgery, followed by robot-assisted laparoscopic prostatectomy or laparoscopic RP and extended pelvic lymph node dissection (ePLND). Routine postoperative pathological examination was performed. According to the results, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT and mpMRI for the diagnosis of PLNM of LAPC were compared. Results: Among the 50 patients, the mean age was 65.5±10.3 years, the preoperative total serum prostate-specific antigen (PSA) was 30.7±12.3 ng/mL, and the Gleason score was 7 [7, 8]. The difference in diagnostic efficacy between 68Ga-PSMA PET/CT and mpMRI in the preoperative diagnosis of PLNM of PCa was determined by postoperative pathological results. Based on the number of patients who developed PLNM, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT were as follows: 93.75%, 100.00%, 100.00%, 97.14%, and 68.75%, 97.06%, 91.67%, 86.84% for mpMRI, respectively. Based on the number of pelvic metastatic lymph nodes, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT were 95.24%, 100.00%, 100.00%, 99.48%, and 65.08%, 99.13%, 89.13%, 96.30% for mpMRI, respectively. It turned out that PET/CT was more sensitive than mpMRI in detecting PLNM of PCa, and the difference was statistically significant. Conclusions: 68Ga-PSMA PET/CT is more sensitive than mpMRI in the detection of PLNM in patients with LAPC. It is a promising method in the diagnosis and preoperative assessment of PLNM in LAPC.

13.
Sci Technol Adv Mater ; 25(1): 2376524, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39108607

RESUMEN

Temperature-dependent plastic deformation behaviors of single crystals of quaternary and ternary equiatomic medium-entropy alloys (MEAs) belonging to the Cr-Mn-Fe-Co-Ni system were investigated in compression at temperatures in the range 9 K to 1373 K. Their critical resolved shear stresses (CRSSs) increase with decreasing temperature below room temperature. There is also a dulling of the temperature dependence of CRSS below 77 K due to dislocation inertial effects that we attribute to a decrease in the phonon drag coefficient. These behaviors were compared with those of previously investigated single crystals of the equiatomic Cr-Co-Ni and Cr-Fe-Co-Ni MEAs, and the equiatomic Cr-Mn-Fe-Co-Ni high-entropy alloy (HEA). The temperature dependence of CRSS and the apparent activation volumes below room temperature can be well described by conventional thermal activation theories of face-centered cubic (FCC) alloys. Above 673 K, there is a small increase in CRSS, which we believe is due to elastic interactions between solutes and mobile dislocations, the so-called Portevin-Le Chatelier (PL) effect. The CRSS at 0 K was obtained by extrapolation of fitted CRSS vs. temperature curves and compared with predictions from solid solution strengthening models of HEA and MEAs.


The novelty of our work entitled 'Analysis of the temperature-dependent plastic deformation of single crystals of quinary, quaternary and ternary equiatomic high- and medium-entropy alloys of the Cr-Mn-Fe-Co-Ni system' can be summarized as follows: The temperature dependences of CRSS were experimentally deduced from bulk single crystals of the six MEAs for the first time, so that fair comparison among the FCC HEA/MEAs is made.

14.
Langmuir ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134089

RESUMEN

It offers bright prospects to develop non-Pt group metal (non-PGM) electrocatalysts in the area of energy storage and conversion. Herein, we reported a simple spatial isolation strategy to synthesize Co-based electrocatalysts, using partially substituted Zn atoms in a ZnCo-ZIF precursor. The "fence" effect that originated from the partially substituted Zn atoms can yield a better isolation of Co atoms, achieving selective loading of Co species on nitrogen-doped porous carbon varying from nanoparticles to single atoms. The low boiling point of Zn enables abundant porous structures to the N-doped carbon substrate after pyrolysis. The best performing single-atom Co catalyst (Co-SAs/N-C) exhibits excellent oxygen reduction reaction activity in alkaline media. As an illustration, the rechargeable liquid Zn-air battery incorporating the Co-SAs/N-C catalyst demonstrates a substantial open circuit voltage of 1.49 V, a high specific capacity of 689.3 mAh g-1, and remarkable cycling stability over 200 h. This study paves the way for the strategic development of non-PGM electrocatalysts in battery applications.

15.
Front Pharmacol ; 15: 1446030, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39161903

RESUMEN

Background: Hepatocellular carcinoma accounts for 80% of primary liver cancers, is the most common primary liver malignancy. Hepatocellular carcinoma is the third leading cause of tumor-related deaths worldwide, with a 5-year survival rate of approximately 18%. Chemotherapy, although commonly used for hepatocellular carcinoma treatment, is limited by systemic toxicity and drug resistance. Improving targeted delivery of chemotherapy drugs to tumor cells without causing systemic side effects is a current research focus. Chitosan, a biopolymer derived from chitin, possesses good biocompatibility and biodegradability, making it suitable for drug delivery. Enhanced chitosan formulations retain the anti-tumor properties while improving stability. Chitosan-based biomaterials promote hepatocellular carcinoma apoptosis, exhibit antioxidant and anti-inflammatory effects, inhibit tumor angiogenesis, and improve extracellular matrix remodeling for enhanced anti-tumor therapy. Methods: We summarized published experimental papers by querying them. Results and Conclusions: This review discusses the physicochemical properties of chitosan, its application in hepatocellular carcinoma treatment, and the challenges faced by chitosan-based biomaterials.

16.
Mikrochim Acta ; 191(8): 503, 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39096341

RESUMEN

An upconversion fluorescence sensing platform was developed with upconversion nanoparticles (UCNPs) as energy donors and gold nanoparticles (AuNPs) as energy acceptors, based on the FRET principle. They were used for quantitative detection of uranyl ions (UO22+) by amplifying the signal of the hybrid chain reaction (HCR). When UO22+ are introduced, the FRET between AuNPs and UCNPs can be modulated through a HCR in the presence of high concentrations of sodium chloride. This platform provides exceptional sensitivity, with a detection limit as low as 68 pM for UO22+ recognition. We have successfully validated the reliability of this method by analyzing authentic water samples, achieving satisfactory recoveries (89.00%-112.50%) that are comparable to those of ICP-MS. These results indicate that the developed sensing platform has the capability to identify trace UO22+ in complex environmental samples.

17.
Sleep Health ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39095254

RESUMEN

OBJECTIVES: Environmental risk factors may contribute to sleep-disordered breathing. We investigated the association between indoor particulate matter ≤2.5µm in aerodynamic diameter (PM2.5) and sleep-disordered breathing in children in an urban US community. METHODS: The sample consisted of children aged 6-12years living in predominantly low-income neighborhoods in Boston, Massachusetts. Indoor PM2.5 was measured in participants' main living areas for 7days using the Environmental Multipollutant Monitoring Assembly device. High indoor PM2.5 exposure was defined as greater than the sample weekly average 80th percentile level (≥15.6 µg/m3). Sleep-disordered breathing was defined as an Apnea-Hypopnea-Index (AHI) or Oxygen-Desaturation-Index (ODI) (≥3% desaturation) of ≥5 events/hour. Habitual loud snoring was defined as caregiver-report of loud snoring (most or all the time each week) over the past 4weeks. We examined the associations of PM2.5 with sleep-disordered breathing or snoring using logistic regression adjusting for potential confounders. RESULTS: The sample included 260 children (mean age 9.6years; 41% female), with 32% (n = 76) classified as having sleep-disordered breathing. In a logistic regression model adjusted for socioeconomics and seasonality, children exposed to high indoor PM2.5 levels (n = 53) had a 3.53-fold increased odds for sleep-disordered breathing (95%CI: 1.57, 8.11, p = .002) compared to those with lower indoor PM2.5. This association persisted after additional adjustments for physical activity, outdoor PM2.5, environmental tobacco smoke, and health characteristics. Similar associations were observed for snoring and indoor PM2.5. CONCLUSIONS: Children with higher indoor PM2.5 exposure had greater odds of sleep-disordered breathing and habitual loud snoring, suggesting that indoor air quality contributes to sleep disparities.

18.
Sci China Life Sci ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39153050

RESUMEN

Diabetic foot ulcers (DFUs) are a serious vascular disease. Currently, no effective methods are available for treating DFUs. Pro-protein convertase subtilisin/kexin type 9 (PCSK9) regulates lipid levels to promote atherosclerosis. However, the role of PCSK9 in DFUs remains unclear. In this study, we found that the expression of PCSK9 in endothelial cells (ECs) increased significantly under high glucose (HG) stimulation and in diabetic plasma and vessels. Specifically, PCSK9 promotes the E3 ubiquitin-protein ligase NEDD4 binding to vascular endothelial growth factor receptor 2 (VEGFR2), which led to the ubiquitination of VEGFR2, resulting in its degradation and downregulation in ECs. Furthermore, PCSK9 suppresses the expression and activation of AKT, endothelial nitric oxide synthase (eNOS), and ERK1/2, leading to decreased nitric oxide (NO) production and increased superoxide anion (O2._) generation, which impairs vascular endothelial function and angiogenesis. Importantly, using evolocumab to limit the increase in PCSK9 expression blocked the HG-induced inhibition of NO production and the increase in O2._ production, as well as inhibited the phosphorylation and expression of AKT, eNOS, and ERK1/2. Moreover, evolocumab improved vascular endothelial function and angiogenesis, and promoted wound healing in diabetes. Our findings suggest that targeting PCSK9 is a novel therapeutic approach for treating DFUs.

19.
ChemSusChem ; : e202401186, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39215381

RESUMEN

Fe-N-C single-atom catalysts (SACs) have emerged as one of the most promising candidates for oxygen electrocatalysis due to their maximized atom utilization efficiency, high intrinsic activity, and strong metal-support interaction. Significant progress has been made in engineering Fe-N-C SACs for oxygen electrocatalysis in Zn-air batteries (ZABs). This review provides a comprehensive overview of the recent advancements in Fe-N-C SACs, with a special focus on effective engineering strategies, their performance in oxygen electrocatalysis, and their potential applications in ZABs. The review also discusses the key challenges and future directions in the development of Fe-N-C SACs for efficient and durable oxygen electrocatalysis in ZABs. This review aims to offer valuable insights into the current state of research in this field and to guide future efforts in the development of advanced oxygen electrocatalysts for ZABs.

20.
World J Gastroenterol ; 30(30): 3584-3608, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39193572

RESUMEN

BACKGROUND: Fanlian Huazhuo Formula (FLHZF) has the functions of invigorating spleen and resolving phlegm, clearing heat and purging turbidity. It has been identified to have therapeutic effects on type 2 diabetes mellitus (T2DM) in clinical application. Non-alcoholic fatty liver disease (NAFLD) is frequently diagnosed in patients with T2DM. However, the therapeutic potential of FLHZF on NAFLD and the underlying mechanisms need further investigation. AIM: To elucidate the effects of FLHZF on NAFLD and explore the underlying hepatoprotective mechanisms in vivo and in vitro. METHODS: HepG2 cells were treated with free fatty acid for 24 hours to induce lipid accumulation cell model. Subsequently, experiments were conducted with the different concentrations of freeze-dried powder of FLHZF for 24 hours. C57BL/6 mice were fed a high-fat diet for 8-week to establish a mouse model of NAFLD, and then treated with the different concentrations of FLHZF for 10 weeks. RESULTS: FLHZF had therapeutic potential against lipid accumulation and abnormal changes in biochemical indicators in vivo and in vitro. Further experiments verified that FLHZF alleviated abnormal lipid metabolism might by reducing oxidative stress, regulating the AMPKα/SREBP-1C signaling pathway, activating autophagy, and inhibiting hepatocyte apoptosis. CONCLUSION: FLHZF alleviates abnormal lipid metabolism in NAFLD models by regulating reactive oxygen species, autophagy, apoptosis, and lipid synthesis signaling pathways, indicating its potential for clinical application in NAFLD.


Asunto(s)
Autofagia , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Metabolismo de los Lípidos , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico , Estrés Oxidativo , Transducción de Señal , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/etiología , Animales , Autofagia/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Humanos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Transducción de Señal/efectos de los fármacos , Células Hep G2 , Ratones , Masculino , Estrés Oxidativo/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Lipogénesis/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hepatocitos/patología
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