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1.
Biomaterials ; 313: 122764, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39190941

RESUMEN

Currently, mitochondrial dysfunction caused by oxidative stress is a growing concern in degenerative diseases, notably intervertebral disc degeneration (IVDD). Dysregulation of the balance of mitochondrial quality control (MQC) has been considered the key contributor, while it's still challenging to effectively harmonize different MQC components in a simple and biologically safe way. Hydrogen gas (H2) is a promising mitochondrial therapeutic molecule due to its bio-reductivity and diffusibility across cellular membranes, yet its relationship with MQC regulation remains unknown. Herein, we propose a mitochondrial 'Birth-Death' coordinator achieved by an intelligent hydrogen nanogenerator (Fe@HP-OD), which can sustainably release H2 in response to the unique microenvironment in degenerated IVDs. Both in vitro and in vivo results prove alleviation of cellular oxidative stress and restoration of nucleus pulposus cells function, thereby facilitating successful IVD regeneration. Significantly, this study for the first time proposes the mitochondrial 'Birth-Death' coordination mechanism: 1) attenuation of overactivated mitochondrial 'Death' process (UPRmt and unselective mitophagy); and 2) activation of Adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway for mitochondrial 'Birth-Death' balance (mitochondrial biogenesis and controlled mitophagy). These pioneering findings can fill in the gaps in molecular mechanisms for H2 regulation on MQC homeostasis, and pave the way for future strategies towards restoring equilibrium of MQC system against degenerative diseases.


Asunto(s)
Hidrógeno , Degeneración del Disco Intervertebral , Mitocondrias , Estrés Oxidativo , Hidrógeno/química , Animales , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Regeneración/efectos de los fármacos , Disco Intervertebral/efectos de los fármacos , Humanos , Mitofagia/efectos de los fármacos , Ratas Sprague-Dawley , Masculino , Núcleo Pulposo/metabolismo , Ratas
2.
BMC Med Imaging ; 24(1): 245, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39285354

RESUMEN

OBJECTIVE: To evaluate the prediction value of Dual-energy CT (DECT)-based quantitative parameters and radiomics model in preoperatively predicting muscle invasion in bladder cancer (BCa). MATERIALS AND METHODS: A retrospective study was performed on 126 patients with BCa who underwent DECT urography (DECTU) in our hospital. Patients were randomly divided into training and test cohorts with a ratio of 7:3. Quantitative parameters derived from DECTU were identified through univariate and multivariate logistic regression analysis to construct a DECT model. Radiomics features were extracted from the 40, 70, 100 keV and iodine-based material-decomposition (IMD) images in the venous phase to construct radiomics models from individual and combined images using a support vector machine classifier, and the optimal performing model was chosen as the final radiomics model. Subsequently, a fusion model combining the DECT parameters and the radiomics model was established. The diagnostic performances of all three models were evaluated through receiver operating characteristic (ROC) curves and the clinical usefulness was estimated using decision curve analysis (DCA). RESULTS: The normalized iodine concentration (NIC) in DECT was an independent factor in diagnosing muscle invasion of BCa. The optimal multi-image radiomics model had predictive performance with an area-under-the-curve (AUC) of 0.867 in the test cohort, better than the AUC = 0.704 with NIC. The fusion model showed an increased level of performance, although the difference in AUC (0.893) was not statistically significant. Additionally, it demonstrated superior performance in DCA. For lesions smaller than 3 cm, the fusion model showed a high predictive capability, achieving an AUC value of 0.911. There was a slight improvement in model performance, although the difference was not statistically significant. This improvement was observed when comparing the AUC values of the DECT and radiomics models, which were 0.726 and 0.884, respectively. CONCLUSION: The proposed fusion model combing NIC and the optimal multi-image radiomics model in DECT showed good diagnostic capability in predicting muscle invasiveness of BCa.


Asunto(s)
Invasividad Neoplásica , Tomografía Computarizada por Rayos X , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/patología , Masculino , Femenino , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Anciano , Persona de Mediana Edad , Invasividad Neoplásica/diagnóstico por imagen , Biopsia , Anciano de 80 o más Años , Imagen Radiográfica por Emisión de Doble Fotón/métodos , Curva ROC , Adulto , Radiómica
3.
Artículo en Inglés | MEDLINE | ID: mdl-39322487

RESUMEN

Adeno-associated virus (AAV) has emerged as a fundamental component in the gene therapy landscape, widely acknowledged for its effectiveness in therapeutic gene delivery. The success of AAV-based therapies, such as Luxturna and Zolgensma, underscores their potential as a leading vector in gene therapy. This article provides an in-depth review of the development and mechanisms of AAV vector-based therapies, offering a comprehensive analysis of the latest clinical trial outcomes in central nervous system (CNS) diseases, ocular conditions, and hemophilia, where AAV therapies have shown promising results. Additionally, we discusse the selection of administration methods and serotypes tailored to specific diseases. Our objective is to showcase the innovative applications and future potential of AAV-based gene therapy, laying the groundwork for continued clinical advancements.

4.
Front Cell Dev Biol ; 12: 1485712, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39324072

RESUMEN

[This corrects the article DOI: 10.3389/fcell.2024.1410914.].

5.
Arch Biochem Biophys ; 761: 110158, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39307264

RESUMEN

Exogenous assaults interfere with homeostatic processes in the body by inducing stress responses. Corticosteroid-binding globulin (CBG) binds to stress hormone glucocorticoids to transport and dynamically control their availability to target tissues. In our previous study, we confirmed that CBG is locally produced by Leydig cells in the testes. Here, we explored the potential regulators of CBG using a murine Leydig tumor cell line (mLTC-1). Results indicated that luteinizing hormone (LH) and interleukin-6 (IL-6) were important factors stimulating the release of CBG from mLTC-1 cells. In addition, IL-6 stimulated mLTC-1 cells to release alpha-1 antitrypsin (AAT), a serine proteinase inhibitor (serpin) that affects CBG conformation. The results implied that any challenge that altered LH or IL-6 levels also changed the release and binding status of CBG with steroid hormones in the testicular microenvironment and modulated cellular responses to these stress hormones. In addition, secretory proteomic analysis indicated that the extracellular matrix (ECM), cytoskeleton, and proteasomes were essentially produced by the mLTC-1 cells, and LH evoked the secretion of proteins involved in binding and metabolism. These results emphasize that Leydig cells may undertake more functions than just steroidogenesis, and the regulation of Leydig cells by LH is versatile.

6.
Regen Ther ; 26: 826-830, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39329099

RESUMEN

Platelet rich plasma (PRP) is increasingly used in various fields of medicine, aiming to regeneration and repair damaged tissues, cells and organs. High concentration of bioactive molecules including growth factors, cytokines and chemokines are the rationale of using PRP. The aim of this study is to analyze the effect of frozen on the levels of growth factors. In our study, PRP samples were isolated from 50 healthy volunteers using the Trima Accel blood cell separator. The concentration of growth factors such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF-1) and platelet factor 4 (PF-4) were assessed in fresh PRP and frozen PRP stored at -80 °C for one to twelve months. The study found that count of platelet in all fresh and frozen PRP samples was significantly increased compared to whole blood baseline. There was no significant difference in the concentrations of PDGF-BB, bFGF, VEGF, and PF-4 between fresh and frozen samples. The concentrations of EGF and IGF in Frozen-PRP group were significantly higher than those in Fresh-PRP group. And the storage condition of -80 °C is suitable for PRP, which will not lead to a decrease in growth factors concentration for at least 6 months.

7.
Chem Sci ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39323519

RESUMEN

Nickel-rich layered oxides have great potential for commercial development applications, so it is critical to address their stability over long cycles. Ensuring long-term cycle stability relies heavily on the stability of the interface between the electrode and electrolyte in Li|LiNi0.8Co0.1Mn0.1O2 (NCM811) batteries. In this work, a denser, more stable and thinner nickel-rich cathode/electrolyte interface was constructed by electrolyte engineering with succinonitrile (SN) as an additive. The increase of organic compound content in the formed Ni-rich cathode/electrolyte interface can fully release the stress and strain generated during repetitive charge-discharge processes, and significantly reduce the irreversible phase transition during the nickel-rich cathode charge-discharge processes. Additionally, this interface impedes the breakdown of electrolytes and the dissolution of transition metals. Furthermore, the addition of SN additives also forms a more stable lithium metal anode/electrolyte interface. Notably, batteries containing SN additives (0.5, 1.0 and 1.5 wt%) show excellent electrochemical performance compared to base electrolytes. Particularly, the improvement is most significant with an SN addition of 1.0 wt%. After 250 cycles at 1C rate, the capacity retention rate of the battery improved by 32.8%. Thus, this work provides a new perspective for simultaneously constructing a stable interface of nickel-rich cathode and lithium metal anode with a high energy density in lithium metal batteries.

8.
Front Plant Sci ; 15: 1402677, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39323533

RESUMEN

Introduction: In recent years, with the rapid expansion of ratoon rice production in Hunan, a unique ratoon rice-based production system, forage-grain ratoon rice (FG-RR), has been newly developed. Ratooning rice is a season of rice harvested by utilizing the dormant buds on the rice stubble left after harvesting the first season of rice to sprout and grow. Therefore, the characteristics of stalks themselves are crucial for the production of ratoon rice. The cutting period and higher stubble height directly affect the characteristics of ratoon rice stubbles. Based on this, we conducted the following research. Methods: In 2021 and 2022, field experiments were conducted in central China to study the effects of different cutting periods and stubble height on the regeneration rate and nutrient content of ratoon crops. The treatments included two cutting periods (10 days after heading in the first season and 30 days after heading in the first season, respectively referred to as T10 and T30) and two stubble heights (10 cm and 30 cm, respectively referred to as H10 and H30). Results: Compared with the T30H30 treatment, T10H10 and T10H30 increased grain yield by 48.1%, 41.7%, 73.1%, and 65.2% in the two-year ratoon seasons, while T30H10 reduced grain yield by 30.9% and 19.5% in the two years, respectively. Early cutting increased the panicles, spikelets per panicle, and filled grain rate to varying increase, while higher stubble height increased panicles but decreased spikelet panicle. On the one hand, early cutting and higher stubble height increased the dry and fresh weight, nonstructural carbohydrates (NSCs), organic carbon (C), and nitrogen content of rice stalks, thereby improving the regeneration rate of ratoon rice. On the other hand, early cutting and higher stubble height retention increased the accumulation of nitrogen in rice stubble throughout the entire growth period and facilitated the transport of nitrogen to the mature panicles. Discussion: Therefore, appropriate early cutting and higher stubble height retention are the keys to improving the grain yield and stability of ratoon rice.

10.
Inorg Chem ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39298745

RESUMEN

Developing a bifunctional oxygen electrocatalyst is crucial to improve the reversibility and cycle life of a rechargeable zinc-air battery (RZAB). Here, transition metal phosphides (TMPs) with a leaf-like hierarchical structure and multiphase composition can be synthesized by the "alloying-dealloying-phosphating" strategy. The as-prepared P-NiCo(1:1) electrode takes advantage of its internal dense nanoholes and synergistic effects induced by NiCoP-containing polyphase to reveal multifunctional catalysis, such as OER and ORR. In combination of these advantages, P-NiCo(1:1) exhibits an extremely low OER overpotential of 220 mV at 10 mA cm-2, a higher half-wave potential of 0.79 V for ORR, and a smaller potential difference (ΔE) of 0.66 V. The liquid RZAB with P-NiCo(1:1) as a cathodic bifunctional catalyst delivers a higher open-circuit voltage (OCV), a larger power density of 175 mW cm-2, and longer cycling life for more than 180 h. Even when applied in solid-state flexible RZABs, the lightweight module could start high-power devices. With theoretical confirmation, the major phase NiCoP of P-NiCo(1:1) is helpful to increase the density of states, regulate the d-band center, and decrease the energy barrier to 2.13 eV, which are significantly superior to those of Co2P and Ni2P. It is believable that the synthetic strategy and activity-promoting mechanism acquired from this research can offer a guide to designing a promising rechargeable zinc-air battery system.

11.
Theor Appl Genet ; 137(10): 227, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39299955

RESUMEN

KEY MESSAGE: qPEDS1, a major quantitative trait locus that determines kernel row number during domestication, harbors the proposed causal gene Zm00001d033675, which may affect jasmonic acid biosynthesis and determine the fate of spikelets. Maize domestication has achieved the production of maize with enlarged ears, enhancing grain productivity dramatically. Kernel row number (KRN), an important yield-related trait, has increased from two rows in teosinte to at least eight rows in modern maize. However, the genetic mechanisms underlying this process remain unclear. To understand KRN domestication, we developed a teosinte-maize BC2F7 population by introgressing teosinte into a maize background. We identified one line, Teosinte ear rank1 (Ter1), with only 5-7 kernel rows which is fewer than those in almost all maize inbred lines. We detected two quantitative trait loci underlying Ter1 and fine-mapped the major one to a 300-kb physical interval. Two candidate genes, Zm674 and Zm675, were identified from 26 maize reference genomes and teosinte bacterial artificial chromosome sequences. Finally, we proposed that Ter1 affects jasmonic acid biosynthesis in the developing ear to determine KRN by the fate of spikelets. This study provides novel insights into the genetic and molecular mechanisms underlying KRN domestication and candidates for de novo wild teosinte domestication.


Asunto(s)
Ciclopentanos , Domesticación , Oxilipinas , Fenotipo , Sitios de Carácter Cuantitativo , Zea mays , Zea mays/genética , Zea mays/crecimiento & desarrollo , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Mapeo Cromosómico/métodos , Semillas/genética , Semillas/crecimiento & desarrollo , Genes de Plantas , Fitomejoramiento
12.
Phys Chem Chem Phys ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39300936

RESUMEN

Molecular dynamics simulations have been employed to investigate the folding behavior of a single linear polyethylene (PE) chain containing 1000 backbone carbon atoms under fast quenching based on all-atom and united-atom models. The single-chain folding characteristics were studied in detail for six different force fields by analyzing the evolution of chain conformations, folded structure characterisation, free energy and crystallisation. The results show that the all-trans chain undergoes a similar two-stage chain collapse mechanism during isothermal relaxation at T = 500 K, transitioning from local collapse to global collapse into a molten globule state under different force fields. During fast quenching at 100 K ns-1, the molten globule of all-atom model transitions into a folded, significantly anisotropic ordered structure under AMBER-AA or OPLS-AA force fields, while that of the united-atom model remains unchanged in its globular structure. The chain crystallization evolution indicates that the single chain folds into ordered lamellar structures with higher crystallinity under AMBER-AA and OPLS-AA force fields. In contrast, under the other four force fields, the single chain remains in a stable amorphous state.

13.
Heliyon ; 10(18): e37588, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39309886

RESUMEN

Background: Pancreatic cancer is a serious, usually fatal disease and one of the most aggressive malignancies. Research into whether hormone replacement therapy (HRT) might protect against pancreatic cancer has yielded mixed results. This study aimed to investigate the potential association between HRT and the risk of pancreatic cancer in postmenopausal women. Methods: This population-based, retrospective study extracted data from the US National Inpatient Sample (NIS) 2008-2018. Hospitalized females aged ≥55 years were eligible for inclusion. Associations between HRT, other study variables, and pancreatic cancer diagnosis were determined using univariate and multivariable regression analyses. Results: After 1:4 matching by age, data of postmenopausal women with (n = 35,309) and without (n = 141,236) HRT were included in the analysis. The mean age was 73.4 years. Multivariable analyses showed that women with HRT had significantly decreased odds of pancreatic cancer (adjusted OR [aOR], 0.69, 95 % CI: 0.53-0.90). Compared to patients without HRT, patients with HRT in the 55-64-year-old group (aOR 0.48, 95 % CI: 0.32-0.74), 65-74-year-old group (aOR 0.49, 95 % CI: 0.34-0.71), non-hypertensive group (aOR 0.55, 95 % CI: 0.38-0.79), and non-hyperlipidemia group (aOR 0.59, 95 % CI: 0.42-0.82) had significantly decreased odds of pancreatic cancer. Conclusions: In US postmenopausal women, HRT is associated with a reduced risk of pancreatic cancer, especially those aged 55-74 year. Further study is needed to clarify the mechanisms underlying the associations.

14.
Heliyon ; 10(18): e37832, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39315235

RESUMEN

MiR-105 exerts inhibitory effects on the development and progression of various cancers, including breast cancer, lung cancer, and gastric cancer. Through GEO data analysis, we observed decreased expression of miR-105 in liver cancer tissues compared to adjacent tissues. Furthermore, miR-105 downregulates KIFC1 expression levels by targeting its 3' UTR. KIFC1 (Kinesin Family Member C1), a Protein Coding gene, may play a role in mitotic metaphase plate polymerization and mitotic spindle assembly. However, our findings suggest that this gene could serve as a potential chemotherapeutic target for Liver hepatocellular carcinoma (LIHC). We obtained the LIHC dataset from the TCGA database and genotype Tissue Expression Project (GTEx) normal tissue data for differential analysis. Additionally, we utilized the cBioPortal database, tumor immune single-cell center (TISCH) database, gene set enrichment analysis (GSEA), and R software to investigate the possible functions and mechanisms of KIFC1. These findings were further validated through experiments such as immunohistochemistry and wound healing assays. Our results indicate that KIFC1 might be involved in DNA repair and cell cycle regulation in LIHC cells which subsequently impacts tumor cell proliferation; moreover, miR-105 influences hepatoma cell line proliferation via its interaction with KIFC1. Collectively, these results highlight the potential therapeutic significance of targeting KIFC1 for chemotherapy treatment in LIHC patients.

15.
Talanta ; 281: 126853, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39317068

RESUMEN

In today's society, heavy metal ions and antibiotic contaminants have caused great harm to water systems and human health. In this study, six isostructural lanthanide metal-organic frameworks [Ln(H3imda)2(TPA)(H2O)2](Tb for CUST-881, Eu for CUST-882, Dy for CUST-883, Er for CUST-884, Nd for CUST-885, Sm for CUST-886) were constructed by selecting terephthalic acid (TPA) and 4,5-Imidazoledicarboxylic acid (H3imda) and lanthanide metal ions via solvethermal method. Among them, CUST-881 and CUST-882 can selectively detect Fe3+, Cr2O72-, CrO42, and ceftriaxone sodium (CRO) in water systems and uric acid in urine. CUST-881 shows very low detection limits for these five substances. Furthermore, Principal Component Analysis (PCA) was used to distinguish Fe3+, Cr2O72-, CrO42-, and CRO in water. To our knowledge, this is the first time that they have been able to be simultaneously distinguished. In addition, the possible sensing mechanism was studied through UV-visible spectroscopy, Infrared spectroscopy, and PXRD analysis. Furthermore, the probe also showed satisfactory repeatability and recovery when applied to UA samples that simulated urine. Based on the above results, lanthanide metal-organic frameworks have great potential for practical monitoring of contaminants in water environments.

16.
Zhen Ci Yan Jiu ; 49(8): 797-804, 2024 Aug 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-39318308

RESUMEN

OBJECTIVES: To observe the effect of moxibustion at "Zusanli "(ST36) on the plasma amino acid metabolism in rats with knee osteoarthritis (KOA), and to explore the amino acid metabolism mechanism of moxibustion in repairing cartilage injury in KOA. METHODS: A total of 30 SD rats were randomly divided into normal, model and moxibustion groups, with 10 rats in each group. Rats in the model and moxibustion groups were injected with the mixture of L-cysteine and papain into bilateral knee joint cavity to make the KOA model. The moxibustion group received moxibustion at bilateral ST36 for 30 min, once daily for 30 days. At the end of the experiment, the swelling degree of knee joint was calculated, the mechanical pain threshold was measured by the Von Frey filament, the cartilage tissue injury was observed by HE staining, the matrix metalloproteinase-13 (MMP-13) content in the synovial tissue was detected by enzyme-linked immunosorbent assay (ELISA), and the differential amino acid metabolites in plasma were detected and screened by liquid chromatography-mass spectrometry (LC-MS). RESULTS: Compared with the normal group, the model group showed irregular cartilage surface, decreased number of chondrocytes, uneven distribution, and local clusters of chondrocytes;the contour of the tide line was blurred. The degree of joint swelling in the model group was higher than that in the normal group (P<0.01), the mechanical pain threshold was lower (P<0.01), and the content of MMP-13 in synovial tissue was higher (P<0.01). The contents of proline and tryptophan in the model group were down-regulated (P<0.01, P<0.05). Compared with the model group, the cartilage tissue damage and knee joint swelling were decreased(P<0.05), mechanical pain threshold was increased(P<0.05), MMP-13 content in synovial tissue and levels of glutamate and histidine expression were decreased (P<0.01, P<0.05). CONCLUSIONS: Moxibustion at ST36 significantly alleviated arthritis-related swelling and pain in KOA model rats, attenuated cartilage damage, and regulated levels of certain plasma amino acid metabolites. Moxibustion may regulate KOA cartilage synthesis and degradation through amino acid metabolic pathways such as proline, tryptophan, glutamate and histidine, exerting anti-inflammatory, analgesic, and protection of cartilage injury effects.


Asunto(s)
Aminoácidos , Moxibustión , Osteoartritis de la Rodilla , Ratas Sprague-Dawley , Animales , Ratas , Osteoartritis de la Rodilla/terapia , Osteoartritis de la Rodilla/metabolismo , Osteoartritis de la Rodilla/sangre , Masculino , Humanos , Aminoácidos/sangre , Aminoácidos/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 13 de la Matriz/sangre , Metaloproteinasa 13 de la Matriz/genética , Puntos de Acupuntura , Modelos Animales de Enfermedad
17.
ACS Nano ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39319775

RESUMEN

Normally, it is hard to regulate thermal defects precisely in their host lattice due to the stochastic nature of thermal activation. Here, we demonstrate a thermal annealing way to create patterned single sulfur vacancy (VS) defects in monolayer molybdenum disulfide (MoS2) with about 2 nm separations at subnanometer accuracy. Theoretically, we reveal that the S-Au interface coupling reduces the energy barriers in forming VS defects and that explains the overwhelming formation of interface VS defects. We also discover a phonon regulation mechanism by the moiré interface that effectively condenses the Γ-point out-of-plane acoustic phonons of monolayer MoS2 to its TOP moiré sites, which has been proposed to trigger moiré-patterned thermal VS formation. The high-throughput nanoscale patterned defects presented here may contribute to building scalable defect-based quantum systems.

18.
Cell Biochem Biophys ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39316262

RESUMEN

Alveolar epithelial cell injury plays a key role in acute lung injury (ALI) and is a vital determinant of its severity. Here, we aimed to assess the protective effects of cinnamaldehyde (CA) on lipopolysaccharide (LPS)-induced A549 cells and elucidate the underlying mechanisms. A549 cells were stimulated with 1 µg/mL LPS for 24 h to establish an alveolar epithelial cell injury model and subsequently treated with CA or Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93. Flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and lactate dehydrogenase release assays were used to evaluate apoptosis, cell viability, and lactate dehydrogenase activity, respectively. Levels of inflammatory cytokines (interleukin-6, interleukin-1ß, tumor necrosis tactor-α, and interferon-γ) and oxidative stress markers (reactive oxygen species, superoxide dismutase, catalase, and malondialdehyde) were determined using enzyme-linked immunosorbent assay and specific assay kits, respectively. Furthermore, levels of apoptosis-related proteins (cleaved caspase-3, Bcl-2-associated X, and Bcl-2) and CaMKII were assessed via western blotting. CA did not exhibit significant cytotoxicity in A549 cells. It dose-dependently improved the cell viability, suppressed apoptosis, decreased cleaved caspase-3 and Bcl-2-associated X levels, and increased Bcl-2 levels in LPS-treated A549 cells. It also inhibited inflammatory factor release and oxidative stress in LPS-induced A549 cells. Similar results were observed in the KN93- and CA-treated groups. Western blotting assay revealed that CA and KN93 inhibited CaMKII pathway activation, as indicated by the reduced p-CaMKII and p-phospholamban (PLN) levels and p-CaMKII/CaMKII and p-PLN/PLN ratios. Overall, CA alleviated alveolar epithelial cell injury by inhibiting the inflammatory response and oxidative stress and inducing cell apoptosis in LPS-induced A549 cells by regulating the CaMKII pathway, serving as a potential candidate for ALI prevention and treatment.

19.
Sci Rep ; 14(1): 20874, 2024 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-39242655

RESUMEN

Persistent subretinal fluid (PSF) after scleral bucking of rhegmatogenous retinal detachment may delay recovery and affect the final visual quality, but with no effective treatment. This study firstly investigated the safety and efficacy of 577 nm yellow subthreshold micropulse laser (SML) on PSF after scleral bucking surgery. This double-masked randomized clinical trial was conducted from December 2020 to October 2022 at Chongqing Aier Eye Hospital. Participants with PSF last for 1 month after scleral bucking surgery with break closed and retina reattachment were recruitment. These participants were treated by 577 nm yellow SML or sham treatment. Funduscopy, optical coherence tomography (OCT) volume change, best corrected vision acuity (BCVA) and visual field test were evaluated for six mouths follow-up. A total of 24 participants were randomized into SML group or Sham group equally. Compared with Sham group, the OCT volume within 6 mm of macular fovea was significantly less in SML group 6 months after therapy (P = 0.048). There were no statistically significant differences of OCT volume at 1, 2 and 3 months from baseline between groups. BCVA of ETDRS letters had no statistically significant difference. Pattern Standard Deviation amelioration (P = 0.039) had statistically significance in SML group compared with Sham group. There were no complications in the 2 groups. These preliminary findings suggest that 577 nm yellow SML therapy could accelerate PSF absorption after scleral bucking surgery.Trial registration: Chinese Clinical Trial Registry No. ChiCTR2000037838, 02/09/2020, https://www.chictr.org.cn/showproj.html?proj=51885 .


Asunto(s)
Desprendimiento de Retina , Curvatura de la Esclerótica , Líquido Subretiniano , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Femenino , Masculino , Curvatura de la Esclerótica/métodos , Curvatura de la Esclerótica/efectos adversos , Desprendimiento de Retina/cirugía , Persona de Mediana Edad , Tomografía de Coherencia Óptica/métodos , Adulto , Resultado del Tratamiento , Método Doble Ciego
20.
Biomater Res ; 28: 0073, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39247653

RESUMEN

The pathogenesis of temporomandibular joint osteoarthritis (TMJOA) is closely associated with mechanical friction, which leads to the up-regulation of inflammatory mediators and the degradation of articular cartilage. Injectable drug-loaded microparticles have attracted widespread interest in intra-articular treatment of TMJOA by providing lubrication and facilitating localized drug delivery. Herein, a hyaluronic acid-based microparticle is developed with excellent lubrication properties, drug loading capacity, antioxidant activity, and anti-inflammatory effect for the treatment of TMJOA. The microparticles are facilely prepared by the self-assembly of 3-aminophenylboronic acid-modified hyaluronic acid (HP) through hydrophobic interaction in an aqueous solution, which can further encapsulate diol-containing drugs through dynamic boronate ester bonds. The resulting microparticles demonstrate excellent injectability, lubrication properties, radical scavenging efficiency, and antibacterial activity. Additionally, the drug-loaded microparticles exhibit a favorable cytoprotective effect on chondrocyte cells in vitro under an oxidative stress microenvironment. In vivo experiments validate that intra-articular injection of drug-loaded microparticles effectively alleviates osteoporosis-like damage, suppresses inflammatory response, and facilitates matrix regeneration in the treatment of TMJOA. The HP microparticles demonstrate excellent injectability and encapsulation capacity for diol-containing drugs, highlighting its potential as a versatile drug delivery vehicle in the intra-articular treatment of TMJOA.

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