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1.
J Clin Lipidol ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39278776

RESUMEN

BACKGROUND: Patients suffering from sitosterolemia with ABCG5/8 mutation typically present with early-onset or rapidly progressive atherosclerosis. Their kindreds with partial genetic deficiencies of ABCG5/8 are often considered healthy. However, discerning sitosterolemia from its familial kindreds and hyperlipidemia subjects has remained challenging. METHODS: Here we retrospectively recruited seven families including 8 individuals diagnosed with sitosterolemia subjects, and 14 kindreds carrying single gene mutations. Additionally, 17 individuals with hyperlipidemia and 130 healthy controls served as positive and negative controls, respectively. A total of 6 phytosterols combined with cholesterol absorption indices (including sitosterol, campesterol, stigmasterol, and cholestanol) and cholesterol synthesis markers (desmosterol and 7-dehydrocholesterol), was compared across the aforementioned four groups. RESULTS: As expected, the sitosterolemia subjects with double mutations demonstrated significantly elevated levels of sitosterol and other cholesterol absorption indices. Meanwhile, sitosterolemia kindreds with single gene mutation showed a similar pattern of activated cholesterol-absorption ability to the hyperlipidemia group, but not as high as the double mutation group. Notably, the cholesterol-synthesis enzyme 7-dehydrocholesterol reductase displayed an increase in the hyperlipidemia group but a decrease in the sitosterolemia kindred group, suggesting a potential discriminative role of 7-dehydrocholesterol in distinguishing between these two groups. The combination of phytosterols was more valuable than clinical lipid index for sitosterolemia diagnosis. CONCLUSION: Our study revealed mild disruptions of cholesterol absorption capacities in sitosterolemia kindreds with single mutations. Furthermore, the combination of 6 phytosterols proved effective in distinguishing between sitosterolemia, its single mutation carriers, and hyperlipidemia patients.

2.
J Imaging Inform Med ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39231885

RESUMEN

Iris recognition, renowned for its exceptional precision, has been extensively utilized across diverse industries. However, the presence of noise and blur frequently compromises the quality of iris images, thereby adversely affecting recognition accuracy. In this research, we have refined the traditional Wiener filter image restoration technique by integrating it with a gradient descent strategy, specifically employing the Barzilai-Borwein (BB) step size selection. This innovative approach is designed to enhance both the precision and resilience of iris recognition systems. The BB gradient method is adept at optimizing the parameters of the Wiener filter by introducing simulated blurring and noise conditions to the iris images. Through this process, it is capable of restoring images that have been degraded by blur and noise, leading to a significant improvement in the clarity of the restored images and, consequently, a notable elevation in recognition performance. The results of our experiments have demonstrated that this advanced method surpasses conventional filtering techniques in terms of both subjective visual quality assessments and objective peak signal-to-noise ratio (PSNR) evaluations.

3.
Int J Nanomedicine ; 19: 7817-7830, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39099790

RESUMEN

Background: Photothermal therapy (PTT) guided by photoacoustic imaging (PAI) using nanoplatforms has emerged as a promising strategy for cancer treatment due to its efficiency and accuracy. This study aimed to develop and synthesize novel second near-infrared region (NIR-II) absorption-conjugated polymer acceptor acrylate-substituted thiadiazoloquinoxaline-diketopyrrolopyrrole polymers (PATQ-DPP) designed specifically as photothermal and imaging contrast agents for nasopharyngeal carcinoma (NPC). Methods: The PATQ-DPP nanoparticles were synthesized and characterized for their optical properties, including low optical band gaps. Their potential as PTT agents and imaging contrast agents for NPC was evaluated both in vitro and in vivo. The accumulation of nanoparticles at tumor sites was assessed post-injection, and the efficacy of PTT under near-infrared laser irradiation was investigated in a mouse model of NPC. Results: Experimental results indicated that the PATQ-DPP nanoparticles exhibited significant photoacoustic contrast enhancement and favorable PTT performance. Safety and non-toxicity evaluations confirmed the biocompatibility of these nanoparticles. In vivo studies showed that PATQ-DPP nanoparticles effectively accumulated at NPC tumor sites and demonstrated excellent tumor growth inhibition upon exposure to near-infrared laser irradiation. Notably, complete elimination of nasopharyngeal tumors was observed within 18 days following PTT. Discussion: The findings suggest that PATQ-DPP nanoparticles are a promising theranostic agent for NIR-II PAI and PTT of tumors. This innovative approach utilizing PATQ-DPP nanoparticles provides a powerful tool for the early diagnosis and precise treatment of NPC, offering a new avenue in the management of this challenging malignancy.


Asunto(s)
Nanopartículas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Técnicas Fotoacústicas , Terapia Fototérmica , Animales , Técnicas Fotoacústicas/métodos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/diagnóstico por imagen , Terapia Fototérmica/métodos , Ratones , Línea Celular Tumoral , Humanos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/diagnóstico por imagen , Nanopartículas/química , Rayos Infrarrojos , Ratones Desnudos , Medios de Contraste/química , Ratones Endogámicos BALB C , Polímeros/química , Femenino
4.
Artículo en Inglés | MEDLINE | ID: mdl-38990083

RESUMEN

Hypertension has become a major contributor to the morbidity and mortality of cardiovascular diseases worldwide. Despite the evidence of the anti-hypertensive effect of gastrodia-uncaria granules (GUG) in hypertensive patients, little is known about its potential therapeutic targets as well as the underlying mechanism. GUG components were sourced from TCMSP and HERB, with bioactive ingredients screened. Hypertension-related targets were gathered from DisGeNET, OMIM, GeneCards, CTD, and GEO. The STRING database constructed a protein-protein interaction network, visualized by Cytoscape 3.7.1. Core targets were analyzed via GO and KEGG using R package ClusterProfiler. Molecular docking with AutodockVina 1.2.2 revealed favorable binding affinities. In vivo studies on hypertensive mice and rats validated network pharmacology findings. GUG yielded 228 active ingredients and 1190 targets, intersecting with 373 hypertension-related genes. PPI network analysis identified five core genes: AKT1, TNF-α, GAPDH, IL-6, and ALB. Top enriched GO terms and KEGG pathways associated with the anti-hypertensive properties of GUG were documented. Molecular docking indicated stable binding of core components to targets. In vivo study showed that GUG could improve vascular relaxation, alleviate vascular remodeling, and lower blood pressure in hypertensive animal models possibly through inhibiting inflammatory factors such as AKT1, mTOR, and CCND1. Integrated network pharmacology and in vivo experiment showed that GUG may exert anti-hypertensive effects by inhibiting inflammation response, which provides some clues for understanding the effect and mechanisms of GUG in the treatment of hypertension.

5.
Sci Rep ; 14(1): 16400, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39013923

RESUMEN

In order to further promote the application of cementitious sand gravel (CSG), the mechanical properties and variation rules of CSG material under triaxial test were studied. Considering the influence of fly ash content, water-binder ratio, sand rate and lateral confining pressure, 81 cylinder specimens were designed and made for conventional triaxial test, and the influence laws of stress-strain curve, failure pattern, elastic modulus, energy dissipation and damage evolution of specimens were analyzed. The results showed that the peak of stress-strain curve increased with the increase of confining pressure, and the peak stress, peak strain and energy dissipation all increased significantly, but the damage variable D decreased with the increase of confining pressure. Under triaxial compression, the specimen was basically sheared failure from the bonding surface, and the aggregate generally did not break. Sand rate had a significant effect on the peak stress of CSG, and decreased with the increase of sand rate. Under the conditions of the same cement content, fly ash content and confining pressure, the optimal water-binder ratio 1.2 existed when the sand rate was 0.2 and 0.3. After analyzing and processing the stress-strain curve of triaxial test, a Cuckoo Search-eXtreme Gradient Boosting (CS-XGBoost) curve prediction model was established, and the model was evaluated by evaluation indexes R2, RMSE and MAE. The average R2 of the XGBoost model based on initial parameters under 18 different output features was 0.8573, and the average R2 of the CS-XGBoost model was 0.9516, an increase of 10.10%. Moreover, the prediction curve was highly consistent with the test curve, indicating that the CS algorithm had significant advantages. The CS-XGBoost model could accurately predict the triaxial stress-strain curve of CSG.

6.
Environ Res ; 258: 119415, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38906446

RESUMEN

BACKGROUND: PM2.5, a known public health risk, is increasingly linked to intestinal disorders, however, the mechanisms of its impact are not fully understood. PURPOSE: This study aimed to explore the impact of chronic PM2.5 exposure on intestinal barrier integrity and to uncover the underlying molecular mechanisms. METHODS: C57BL/6 J mice were exposed to either concentrated ambient PM2.5 (CPM) or filtered air (FA) for six months to simulate urban pollution conditions. We evaluated intestinal barrier damage, microbial shifts, and metabolic changes through histopathology, metagenomics, and metabolomics. Analysis of the TLR signaling pathway was also conducted. RESULTS: The mean concentration of PM2.5 in the CPM exposure chamber was consistently measured at 70.9 ± 26.8 µg/m³ throughout the study period. Our findings show that chronic CPM exposure significantly compromises intestinal barrier integrity, as indicated by reduced expression of the key tight junction proteins Occludin and Tjp1/Zo-1. Metagenomic sequencing revealed significant shifts in the microbial landscape, identifying 35 differentially abundant species. Notably, there was an increase in pro-inflammatory nongastric Helicobacter species and a decrease in beneficial bacteria, such as Lactobacillus intestinalis, Lactobacillus sp. ASF360, and Eubacterium rectale. Metabolomic analysis further identified 26 significantly altered metabolites commonly associated with intestinal diseases. A strong correlation between altered bacterial species and metabolites was also observed. For example, 4 Helicobacter species all showed positive correlations with 13 metabolites, including Lactate, Bile acids, Pyruvate and Glutamate. Additionally, increased expression levels of TLR2, TLR5, Myd88, and NLRP3 proteins were noted, and their expression patterns showed a strong correlation, suggesting a possible involvement of the TLR2/5-MyD88-NLRP3 signaling pathway. CONCLUSIONS: Chronic CPM exposure induces intestinal barrier dysfunction, microbial dysbiosis, metabolic imbalance, and activation of the TLR2/5-MyD88-NLRP3 inflammasome. These findings highlight the urgent need for intervention strategies to mitigate the detrimental effects of air pollution on intestinal health and identify potential therapeutic targets.


Asunto(s)
Disbiosis , Inflamasomas , Ratones Endogámicos C57BL , Factor 88 de Diferenciación Mieloide , Proteína con Dominio Pirina 3 de la Familia NLR , Material Particulado , Receptor Toll-Like 2 , Receptor Toll-Like 5 , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Disbiosis/inducido químicamente , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Material Particulado/toxicidad , Factor 88 de Diferenciación Mieloide/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Receptor Toll-Like 2/metabolismo , Ratones , Receptor Toll-Like 5/metabolismo , Contaminantes Atmosféricos/toxicidad , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Intestinos/efectos de los fármacos , Intestinos/microbiología
7.
Biomed Opt Express ; 15(6): 3962-3974, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38867767

RESUMEN

Adjuvants are indispensable ingredients in vaccine formulations. Evaluating the in vivo transport processes of adjuvants, particularly for inhalation formulations, presents substantial challenges. In this study, a nanosized adjuvant aluminum hydroxide (AlOOH) was synthesized and labeled with indocyanine green (ICG) and bovine serum albumin (BSA) to achieve strong optical absorption ability and high biocompatibility. The adjuvant nanomaterials (BSA@ICG@AlOOH, BIA) were delivered as an aerosol into the airways of mice, its distribution was monitored using photoacoustic imaging (PAI) in vivo. PAI results illustrated the gradual cross-layer transmission process of BIA in the tracheal layer, traversing approximately 250 µm from the inner layer of the trachea to the outer layer. The results were consistent with pathology. While the intensity of the BIA reduced by approximately 46.8% throughout the transport process. The ability of PAI for quantitatively characterized the dynamic transport process of adjuvant within the tracheal layer may be widely used in new vaccine development.

8.
Mol Med Rep ; 30(1)2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38785153

RESUMEN

17ß­estradiol (E2) can inhibit cardiac fibrosis in female patients with heart failure (HF) and activate cell division cycle 42 (Cdc42), however it is unknown whether 17ß­estradiol (E2) can ameliorate differentiation and collagen synthesis in TGF­ß1­stimulated mouse cardiac fibroblasts (MCFs) by regulating cell division cycle 42 (Cdc42). The present study aimed to investigate the roles of estrogen and Cdc42 in preventing myocardial fibrosis and the underlying molecular mechanisms. An ELISA was used to measure the levels of E2 and Cdc42 in the serum of patients with heart failure (HF), and western blotting was used to measure the expression levels of Cdc42 in TGF­ß1­stimulated immortalized MCFs. MCFs were transfected with a Cdc42 overexpression (OE) lentivirus or small interfering RNA (siRNA), or treated with a Cdc42 inhibitor (MLS­573151), and the function of Cdc42 was assessed by western blotting, immunofluorescence staining, reverse transcription­quantitative PCR and dual­luciferase reporter assays. Western blotting and immunofluorescence staining were performed to verify the protective effect of E2 on TGF­ß1­stimulated MCFs, and the association between the protective effect and Cdc42. The results demonstrated that Cdc42 levels were increased in the serum of patients with HF and were positively correlated with the levels of E2; however, Cdc42 levels were decreased in TGF­ß1­stimulated MCFs. Cdc42 inhibited MCF differentiation and collagen synthesis, as indicated by the protein expression of α­smooth muscle actin, collagen I and collagen III. Mechanistically, Cdc42 inhibited the transcription of TGF­ß1 by promoting the expression of p21 (RAC1)­activated kinase 1 (Pak1)/JNK/c­Jun signaling pathway proteins and inhibiting the activity of the Tgfb1 gene promoter. In addition, E2 inhibited the differentiation and collagen synthesis of TGF­ß1­stimulated MCFs, and promoted the protein expression of Pak1, JNK and c­Jun, consistent with the effects of Cdc42, whereas the effects of E2 were abolished when Cdc42 was knocked down. The aforementioned findings suggested that E2 could inhibit differentiation and collagen synthesis in TGF­ß1­stimulated MCFs by regulating Cdc42 and the downstream Pak1/JNK/c­Jun signaling pathway.


Asunto(s)
Diferenciación Celular , Colágeno , Estradiol , Estrógenos , Fibroblastos , Factor de Crecimiento Transformador beta1 , Proteína de Unión al GTP cdc42 , Proteína de Unión al GTP cdc42/metabolismo , Proteína de Unión al GTP cdc42/genética , Animales , Diferenciación Celular/efectos de los fármacos , Ratones , Factor de Crecimiento Transformador beta1/metabolismo , Humanos , Colágeno/metabolismo , Colágeno/biosíntesis , Femenino , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Estrógenos/farmacología , Estradiol/farmacología , Persona de Mediana Edad , Miocardio/metabolismo , Insuficiencia Cardíaca/metabolismo , Masculino , Transducción de Señal/efectos de los fármacos
9.
J Org Chem ; 89(11): 8267-8271, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38752624

RESUMEN

A fluorescence lifetime imaging microscopy (FLIM) technique characterizes surfactant-dependent partitioning of organics in a system that mimics a Negishi-like cross-coupling reaction in water, under synthetic concentrations, with emulsion droplets. Experimental partitioning data were not predictable from simple hydrophilic-lipophilic balances. The ionic surfactant cetrimonium chloride suppressed the reactivity of the metallic zinc surface, presumably through competitive chloride binding and concurrent cetrimonium coating, a finding that may contribute to the reduced performance of ionic surfactants in the bench-scale coupling reaction.

10.
BMJ Open ; 14(5): e083106, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724057

RESUMEN

OBJECTIVES: To investigate the relationships among caregiver burden, family resilience, and caregiver capacity in the care of stroke survivors. We hypothesised that family resilience would mediate the relationship between caregiver burden and caregiver capacity. DESIGN: A cross-sectional study design was used. SETTING: The study was conducted in a tertiary care setting in Ningbo City, Zhejiang Province, China. PARTICIPANTS: The study involved 413 stroke survivors and their primary caregivers. OUTCOME MEASURES: The primary caregivers completed the Shortened Chinese Version of the Family Resilience Assessment Scale, Zarit Caregiver Burden Interview and Family Caregiver Task Inventor and provided their sociodemographic information. Stroke survivors were assessed for activities of daily living, and their sociodemographic information was provided. Data were analysed, controlling for sociodemographic variables and focusing on the mediating effect of family resilience. RESULTS: Caregiver burden was influenced by the activities of daily living of stroke survivors, caregiver age and caregiver health status (p<0.05). Higher caregiver burden was associated with lower family resilience (p<0.01). Lower caregiver capacity corresponded to heavier caregiver burden (p<0.01). Family resilience mediated the relationship between caregiver burden and caregiver capacity (b=0.1568; 95% CI: 0.1063 to 0.2385). CONCLUSIONS: Enhancing family resilience can reduce caregiver burden and improve caregiver capacity in stroke care. These findings underscore the importance of developing interventions focused on nursing skills and family resilience.


Asunto(s)
Actividades Cotidianas , Carga del Cuidador , Cuidadores , Resiliencia Psicológica , Accidente Cerebrovascular , Sobrevivientes , Humanos , Estudios Transversales , Masculino , Femenino , Persona de Mediana Edad , Accidente Cerebrovascular/psicología , Accidente Cerebrovascular/enfermería , China , Cuidadores/psicología , Anciano , Sobrevivientes/psicología , Carga del Cuidador/psicología , Adulto , Familia/psicología , Adaptación Psicológica
11.
APMIS ; 132(8): 571-580, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38798084

RESUMEN

The clinical data from 118 CTD patients with bronchiectasis were collected and categorized into two groups: pulmonary infection present (n = 67) and absent (n = 51), for comparative analysis of characteristics and risk factors. Then, we analyzed and compared their demographics, disease characteristics, and risk factors for infection. Among the whole cohort (n = 118), the incidence of pulmonary infections was 56.78%. The occurrence of rheumatoid arthritis, systemic lupus erythematosus, and vasculitis was found to be associated with an increased risk of pulmonary infection. Sputum culture identified Pseudomonas aeruginosa and Klebsiella pneumoniae as the predominant pathogens in the infected group. Notably, symptoms such as joint pains (p = 0.018) and morning stiffness (p = 0.017) were significantly more common in the infected group compared to the noninfected group. Moreover, our findings revealed that elevated levels of C-reactive protein and complement C3, along with bronchial expansion observed on high-resolution computed tomography (HRCT), were significant independent factors in the infection group. Conversely, pulmonary interstitial changes identified through HRCT (OR: 0.135, 95% CI: 0.030-0.612, p = 0.009) were significantly associated with the non-infection group. Overall, this study provides valuable insights into managing CTD patients with bronchiectasis, emphasizing early detection and tailored approaches to prevent and treat pulmonary infections for better outcomes.


Asunto(s)
Bronquiectasia , Enfermedades del Tejido Conjuntivo , Humanos , Bronquiectasia/complicaciones , Masculino , Femenino , Factores de Riesgo , Persona de Mediana Edad , Enfermedades del Tejido Conjuntivo/complicaciones , Adulto , Anciano , Tomografía Computarizada por Rayos X , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Pseudomonas aeruginosa/aislamiento & purificación , Incidencia , Esputo/microbiología , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/complicaciones , Estudios Retrospectivos , Complemento C3/análisis , Complemento C3/metabolismo
12.
J Mol Model ; 30(5): 131, 2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38613643

RESUMEN

CONTEXT: SHP2 is a non-receptor protein tyrosine phosphatase to remove tyrosine phosphorylation. Functionally, SHP2 is an essential bridge to connect numerous oncogenic cell-signaling cascades including RAS-ERK, PI3K-AKT, JAK-STAT, and PD-1/PD-L1 pathways. This study aims to discover novel and potent SHP2 inhibitors using a hierarchical structure-based virtual screening strategy that combines molecular docking and the fragment molecular orbital method (FMO) for calculating binding affinity (referred to as the Dock-FMO protocol). For the SHP2 target, the FMO method prediction has a high correlation between the binding affinity of the protein-ligand interaction and experimental values (R2 = 0.55), demonstrating a significant advantage over the MM/PBSA (R2 = 0.02) and MM/GBSA (R2 = 0.15) methods. Therefore, we employed Dock-FMO virtual screening of ChemDiv database of ∼2,990,000 compounds to identify a novel SHP2 allosteric inhibitor bearing hydroxyimino acetamide scaffold. Experimental validation demonstrated that the new compound (E)-2-(hydroxyimino)-2-phenyl-N-(piperidin-4-ylmethyl)acetamide (7188-0011) effectively inhibited SHP2 in a dose-dependent manner. Molecular dynamics (MD) simulation analysis revealed the binding stability of compound 7188-0011 and the SHP2 protein, along with the key interacting residues in the allosteric binding site. Overall, our work has identified a novel and promising allosteric inhibitor that targets SHP2, providing a new starting point for further optimization to develop more potent inhibitors. METHODS: All the molecular docking studies were employed to identify potential leads with Maestro v10.1. The protein-ligand binding affinities of potential leads were further predicted by FMO calculations at MP2/6-31G* level using GAMESS v2020 system. MD simulations were carried out with AmberTools18 by applying the FF14SB force field. MD trajectories were analyzed using VMD v1.9.3. MM/GB(PB)SA binding free energy analysis was carried out with the mmpbsa.py tool of AmberTools18. The docking and MD simulation results were visualized through PyMOL v2.5.0.


Asunto(s)
Acetamidas , Simulación de Dinámica Molecular , Fosfatidilinositol 3-Quinasas , Ligandos , Simulación del Acoplamiento Molecular
13.
Heliyon ; 10(7): e28796, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38633655

RESUMEN

Pollution characteristics, distribution, risk and sources of 7 heavy metals in sediments of Yangtze River Estuary were investigated. Total concentration ranges of As, Cr, Cu, Cd, Pb, Zn and Ni were [0, 16.5], [1.48, 51.3], [2.66, 318], [0, 0.99], [35.6, 992], [8, 91.3] and [1.88, 108] mg/kg, respectively. Based on the potential ecological risk index and Geoaccumulation index, it was determined that Pb is the most polluted heavy metal. According to class I standard of "Marine sediment quality" of China, mean baseline levels multiples were Pb (8.34) > Cu (0.57) > Cr (0.37) > Zn (0.355) > Ni (0.352) > As (0.28) > Cd (0.00). The study also found the heavy metal content of Pb is the most serious, but most of the Pb content comes from the residual state, which has minimal impact on the environment. The East Nanhui Shoal was identified as the most polluted sub-area in terms of Pb pollution, followed by other specific locations. Considering the pollution level and transport costs, the study concluded that dredge soils of the Yangtze River Estuary Deepwater Channel are not suitable for the restoration of East Hengsha Shoal.

14.
Cell Discov ; 10(1): 43, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38622126

RESUMEN

Macroautophagy is a process that cells engulf cytosolic materials by autophagosomes and deliver them to lysosomes for degradation. The biogenesis of autophagosomes requires ATG2 as a lipid transfer protein to transport lipids from existing membranes to phagophores. It is generally believed that endoplasmic reticulum is the main source for lipid supply of the forming autophagosomes; whether ATG2 can transfer lipids from other organelles to phagophores remains elusive. In this study, we identified a new ATG2A-binding protein, ANKFY1. Depletion of this endosome-localized protein led to the impaired autophagosome growth and the reduced autophagy flux, which largely phenocopied ATG2A/B depletion. A pool of ANKFY1 co-localized with ATG2A between endosomes and phagophores and depletion of UVRAG, ANKFY1 or ATG2A/B led to reduction of PI3P distribution on phagophores. Purified recombinant ANKFY1 bound to PI3P on membrane through its FYVE domain and enhanced ATG2A-mediated lipid transfer between PI3P-containing liposomes. Therefore, we propose that ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores. This finding implicates a new lipid source for ATG2A-mediated phagophore expansion, where endosomes donate PI3P and other lipids to phagophores via lipid transfer.

15.
Reprod Biol Endocrinol ; 22(1): 51, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671458

RESUMEN

BACKGROUND: Ovarian damage and follicle loss are major side effects of chemotherapy in young female patients with cancer. However, effective strategies to prevent these injuries are still lacking. The purpose of this study was to verify low-intensity pulsed ultrasound (LIPUS) can reduce ovarian injury caused by chemotherapy and to explore its underlying mechanisms in mice model. METHODS: The mice were randomly divided into the Control group, Cisplatin group, and Cisplatin + LIPUS group. The Cisplatin group and Cisplatin + LIPUS group were intraperitoneally injected with cisplatin every other day for a total of 10 injections, and the Control group was injected with saline. On the second day of each injection, the Cisplatin + LIPUS group received irradiation, whereas the other two groups received sham irradiation. We used a variety of biotechnologies to detect the differences in follicle count, granulosa cell apoptosis, fibrosis, transcriptome level, oxidative damage, and inflammation in differently treated mice. RESULT: LIPUS was able to reduce primordial follicle pool depletion induced by cisplatin and inhibit the apoptosis of granulosa cells. Transcriptomic results confirmed that LIPUS can reduce ovarian tissue injury. We demonstrated that LIPUS can relieve ovarian fibrosis by inhibiting TGF-ß1/Smads pathway. Meanwhile, it can reduce the oxidative damage and reduced the mRNA levels of proinflammatory cytokines caused by chemotherapy. CONCLUSION: LIPUS can reduce the toxic effects of chemotherapy drugs on ovaries, inhibit ovarian fibrosis, reduce the inflammatory response, and redcue the oxidative damage, reduce follicle depletion and to maintain the number of follicle pools.


Asunto(s)
Antineoplásicos , Cisplatino , Ovario , Ondas Ultrasónicas , Animales , Femenino , Ratones , Cisplatino/efectos adversos , Ovario/efectos de los fármacos , Ovario/efectos de la radiación , Ovario/patología , Antineoplásicos/efectos adversos , Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Folículo Ovárico/efectos de los fármacos , Folículo Ovárico/efectos de la radiación , Terapia por Ultrasonido/métodos
16.
Biomater Sci ; 12(9): 2229-2243, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38497247

RESUMEN

Nanozymes, a distinctive class of nanomaterials endowed with enzyme-like activity and kinetics akin to enzyme-catalysed reactions, present several advantages over natural enzymes, including cost-effectiveness, heightened stability, and adjustable activity. However, the conventional trial-and-error methodology for developing novel nanozymes encounters growing challenges as research progresses. The advent of artificial intelligence (AI), particularly machine learning (ML), has ushered in innovative design approaches for researchers in this domain. This review delves into the burgeoning role of ML in nanozyme research, elucidating the advancements achieved through ML applications. The review explores successful instances of ML in nanozyme design and implementation, providing a comprehensive overview of the evolving landscape. A roadmap for ML-assisted nanozyme research is outlined, offering a universal guideline for research in this field. In the end, the review concludes with an analysis of challenges encountered and anticipates future directions for ML in nanozyme research. The synthesis of knowledge in this review aims to foster a cross-disciplinary study, propelling the revolutionary field forward.


Asunto(s)
Aprendizaje Automático , Nanoestructuras , Nanoestructuras/química , Enzimas/química , Enzimas/metabolismo , Humanos
17.
ACS Omega ; 9(4): 4966-4973, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38313480

RESUMEN

The slurry phase, foam phase, and slurry-foam phase interfaces are the typical locations for bubble-particle detachment, and significant advancements have been achieved in the detachment theory of the slurry phase and foam phase. However, the microscopic detachment mechanism of particles at the slurry-foam phase interface is still unclear. Specifically, there is still debate concerning the collision detachment mechanism of bubble-particle aggregates. Thus, this work investigated the effects of particle size and hydrophobicity on bubble-particle collision detachment. First, a tensiometer detected the detachment force between particles and bubbles. Next, using a high-speed dynamic camera, the collision detachment probability and detachment behavior of bubble-particle aggregates at the interface (solid surface) were statistically recorded and captured. Last, MATLAB software was used to analyze the trajectory and velocity of the particles and the velocity and projected area of the bubbles in the process of bubble-particle collision detachment. This allows for a deeper investigation of the mechanism underlying the detachment of particles of various sizes and hydrophobicity. It is discovered that as particle hydrophobicity increases, the probability of bubble-particle collision detachment reduces. This is because when particle hydrophobicity increases, so does the interaction force between particles and bubbles, improving the stability of the bubble-particle aggregates. Simultaneously, it is discovered that there are notable differences in the collision detachment mechanisms of various particle sizes. Due to their low gravity, the fine particles in the bubble-particle aggregate will slide down the bubble's surface when it collides with the solid surface. This differential velocity motion between the particle and the bubble plays a significant role in the fine particles' detachment. However, the gravity of the coarse particles is strong enough to squeeze the bubbles vertically, and bubble oscillation is an important reason for the detachment of the bubble-particle aggregates. The study's findings advance our understanding of the bubble-particle collision detachment mechanism and offer a theoretical direction for investigating collision detachment behavior at the real slurry-foam phase interface.

18.
Heliyon ; 10(3): e25066, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38314292

RESUMEN

This study describes a method for real-time examination of the microvascular system based on the three-dimensional photoacoustic imaging system to prevent arterial complications, especially vascular embolism, during hyaluronic acid (HA) injections. Chicken embryos were used to simulate the superficial blood vessels of human skin, and then the target area was imaged by the photoacoustic imaging system for three-dimensional vascular imaging, and then the syringe and blood vessels were monitored, and the syringe angle and penetration depth were adjusted in time using an injection device to avoid puncturing the arterial vasculature and clogging the blood vessels. HA was then injected into smaller vessels on the dorsum of the tongue in mice and into thicker vessels on the dorsal portion of the tongue in rats to mimic embolization, and the post-operative recovery was reflected by the changes in the pixel dots of the extracted part of the blocked blood vessels, and it was observed that the blood flow in the area of the fine vessels was restored in about 3 days, whereas blood flow in the area of the large vessels was restored in only about 1 h. The method presented in this paper allows precise guidance of injectable filler HA, which has good application prospects in improving the safety of injection micro-plastic surgery and reducing the experience requirements for medical personnel.

19.
Cell Signal ; 117: 111088, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38316267

RESUMEN

BACKGROUND AND OBJECTIVE: Hypertensive nephropathy is the second leading cause of end-stage renal disease, but its underlying pathogenesis remains unclear. Therefore, this study aimed to explore whether transmembrane protein 16 A (TMEM16A), the molecular basis of calcium-activated chloride channels (CaCC), is involved in the development and progression of hypertensive nephropathy. METHODS: In vivo and in vitro experiments were conducted using a hypertensive murine model and human kidney proximal tubular epithelial cells (HK-2 cells), respectively. EXPERIMENTAL RESULTS: The expression of TMEM16A was down-regulated in renal samples of hypertensive nephropathy patients and hypertensive model mice, accompanied by excessive deposition of extracellular matrix proteins (ECM) such as Fibronectin, Laminin, Collagen I and Collagen III, the up-regulation of α-smooth muscle actin (α-SMA) expression, and the decrease of E-cadherin. Overexpression of TMEM16A or knockdown of TMEM16A inhibited or promoted the expression of Wnt/ß-catenin signaling pathway proteins Wnt3a, LRP5 and active ß-catenin in HK-2 cells, preventing the epithelial-to-mesenchymal transition (EMT) of renal tubules, and the synthesis of ECM components. CONCLUSION: In angiotensin II (Ang II)-induced hypertensive nephropathy, TMEM16A was identified as a key player inhibiting the detrimental changes in renal tubules, suggesting a potential avenue for mitigating renal damage in hypertensive nephropathy.


Asunto(s)
Hipertensión Renal , Nefritis , Vía de Señalización Wnt , Humanos , Ratones , Animales , beta Catenina/metabolismo , Transición Epitelial-Mesenquimal , Proteínas de la Matriz Extracelular , Colágeno , Fibrosis
20.
Artículo en Inglés | MEDLINE | ID: mdl-38409692

RESUMEN

BACKGROUND: Thyroid metastasis arising from primary breast cancer is a rare phenomenon, with only a handful of cases documented in both national and international literature. The management approach and prognosis of this occurrence have sparked debates and uncertainties. CASE PRESENTATION: Herein, we report the case of a 55-year-old woman with breast cancer. She previously underwent extensive excision of the breast lesion with adjuvant chemotherapy and endocrine therapy. After 9 years, she presented with neck discomfort and examination suggested right thyroid metastasis and lymph node metastasis in the neck. Imaging showed pulmonary and bone metastases. Furthermore, the patient received endocrine therapy. After 7 months of follow- up, the patient survived without any new distant metastases. Thyroid metastases originating from breast cancer often unfold with a subtle, intricate nature, making early detection challenging. They tend to emerge inconspicuously, intertwining with widespread systemic metastases, hinting at a less favorable prognosis. CONCLUSION: Given the unusual clinical indicators, identifying heterochronic thyroid metastases in patients with tumors poses a distinct challenge, requiring clinicians to navigate the follow-up process with heightened sensitivity. The key lies in timely detection and early intervention, factors that can significantly enhance the overall quality of life for patients.

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