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1.
J Hazard Mater ; 480: 136365, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39488982

RESUMEN

In natural environments, micro/nanoplastics (MNP) inevitably coexist with various pollutants, making it essential to examine their combined toxicity and intergenerational effects on marine organisms. This study investigated the combined toxicity and intergenerational effects of exposure to triphenyltin (T), microplastics (M), nanoplastics (N), a combination of microplastics and triphenyltin (MT), and a combination of nanoplastics and triphenyltin (NT) on marine medaka. The results showed that all treatments had adverse and intergenerational effects on marine medaka. Regarding oxidative stress and energy metabolism, smaller sized plastic particles caused more significant damage to the organisms. However, MT inflicted greater gonadal system damage than NT, leading to imbalanced sex hormone levels. Additionally, T induced hyperactivity in fish, whereas MNP tended to induce behavioral depression. Notably, large plastic particles in the F0 generation had a more pronounced impact on depressive behaviors compared to smaller particles. These findings suggest that both individual and combined exposures to TPT and MNP can detrimentally affect marine medaka from the molecular to behavioral levels, posing risks to population sustainability. This study provided a robust theoretical foundation and deeper insights into the ecotoxicological impacts and risk assessments of coexisting pollutants.

2.
J Hazard Mater ; 480: 136236, 2024 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-39442301

RESUMEN

Biomolecules, prevalent in the marine environment, can readily adsorb onto the surface of micro(nano)plastics (MNPs), forming eco-corona. This study indicated that 50 nm polystyrene nanoplastics (NP50), whether wrapped with eco-corona or not, can passively enter embryos, whereas 5 µm polystyrene microplastics (MP5) cannot. Additionally, translocation of MP5 from the intestine to the liver was observed in larvae, a process facilitated by eco-corona. Notably, eco-corona prolonged the retention time of MNPs in larvae. However, NP50 was more challenging to purify than MP5, irrespective of the presence of eco-corona. Interestingly, eco-corona degraded in the intestine during the uptake of MNPs, and the hard coronae that readily formed on NP50 may restrict the degradation rate. Although NP50 significantly disrupted larval microbiota homeostasis compared with MP5, eco-corona was more likely to exacerbate MP5's damage to the intestine and liver by disrupting microbiota homeostasis. Additionally, NP50 caused more significant damage to immunity and energy metabolism compared with MP5, regardless of the presence of eco-corona. This study revealed that previously overlooked biomolecules in the marine environment can enhance the translocation of MNPs and subsequently exacerbate their toxic effects, providing theoretical support for assessing the ecological risks of MNPs in real environments.

3.
Front Neurol ; 15: 1459555, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39445190

RESUMEN

Background: Myasthenia Gravis (MG) is an autoimmune disease that causes muscle weakness in 80% of patients, most of whom test positive for anti-acetylcholine receptor (AChR) antibodies (AChR-Abs). Predicting and improving treatment outcomes are necessary due to varying responses, ranging from complete relief to minimal improvement. Objective: Our study aims to develop and validate an interpretable machine learning (ML) model that integrates systemic inflammation indices with traditional clinical indicators. The goal is to predict the short-term prognosis (after 6 months of treatment) of AChR-Ab+ generalized myasthenia gravis (GMG) patients to guide personalized treatment strategies. Methods: We performed a retrospective analysis on 202 AChR-Ab+ GMG patients, dividing them into training and external validation cohorts. The primary outcome of this study was the Myasthenia Gravis Foundation of America (MGFA) post-intervention status assessed after 6 months of treatment initiation. Prognoses were classified as "unchanged or worse" for a poor outcome and "improved or better" for a good outcome. Accordingly, patients were categorized into "good outcome" or "poor outcome" groups. In the training cohort, we developed and internally validated various ML models using systemic inflammation indices, clinical indicators, or a combination of both. We then carried out external validation with the designated cohort. Additionally, we assessed the feature importance of our most effective model using the Shapley Additive Explanations (SHAP) method. Results: In our study of 202 patients, 28.7% (58 individuals) experienced poor outcomes after 6 months of standard therapy. We identified 11 significant predictors, encompassing both systemic inflammation indexes and clinical metrics. The extreme gradient boosting (XGBoost) model demonstrated the best performance, achieving an area under the receiver operating characteristic (ROC) curve (AUC) of 0.944. This was higher than that achieved by logistic regression (Logit) (AUC: 0.882), random forest (RF) (AUC: 0.917), support vector machines (SVM) (AUC: 0.872). Further refinement through SHAP analysis highlighted five critical determinants-two clinical indicators and three inflammation indexes-as crucial for assessing short-term prognosis in AChR-Ab+ GMG patients. Conclusion: Our analysis confirms that the XGBoost model, integrating clinical indicators with systemic inflammation indexes, effectively predicts short-term prognosis in AChR-Ab+ GMG patients. This approach enhances clinical decision-making and improves patient outcomes.

4.
J Pediatr Urol ; 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39426898

RESUMEN

INTRODUCTION: The most common congenital genital abnormality of the urinary system in infants is hypospadias; its frequency is rising to 0.33 percent globally. Surgical reconstruction is the most effective treatment for hypospadias.Parents, as surrogate decision-makers for children, frequently experience decision-making conflicts when making decisions. Stress is neither a straightforward stimulus nor a simple response. However, a stressor (stimulus) caused by life events and influenced by numerous intermediate factors including personality, social support, and psychosomatic symptoms or diseases is a multi-factor process of stress response (response). The surgical decision conflict of parents of children with hypospadias is a type of stress response, and social support may have an effect on parents' hope, psychological resilience, and decision conflict, with hope and psychological resilience serving as mediators between social support and decision conflict. AIM: To investigate the structural relationship between parental social support, hope, psychological resilience, and parents decision conflict in children with hypospadias. STUDY DESIGN: A cross-sectional design was used to collect the data of 210 parents of children with hypospadias from Department of Urology, Shenzhen Children's Hospital from April 2022 to March 2023. RESULTS: Social support indirectly affects decision conflict through hope and psychological resilience, with a total indrect effect of -0.511 (P < 0.05). DISCUSSION: Decision conflicts and regret can be reduced if medical professionals provide adequate and clear information, decision assistance, and meet support requirements during the decision-making process. Improving the level of psychological resilience, hope, and social support among parents of children with hypospadias is a crucial strategy for reducing the level of decision conflict they experience. In the process of making surgical decisions for children with hypospadias, the more sufficient social support from relatives, friends, and medical staff can stimulate their hope, boost their belief in the success of surgery, and the greater their psychological resilience, the more effectively decision conflict can be reduced. Some potential limitations of this study should be considered. Firstly, this study was a cross-sectional survey design. It may have some limitations in providing causal relationships between selected variables. Second, the survey investigated only one hospital, which reduces the generalizability of the findings. CONCLUSION: The data support the proposed model and confirm the structural relationship among the four study variables. This study provides new information on the mediating role of hope and psychological resilience between social support and decision-making conflict.

5.
Funct Plant Biol ; 512024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39401229

RESUMEN

Freeze-thaw is a common stress at high altitudes in northern China. There is a risk of cadmium (Cd) contamination in the region. γ-aminobutyric acid (GABA) is a natural product that regulates plant growth. Rye (Secale cereale ) was used as research material to investigate the physiological effects of exogenous GABA on rye seedlings under the single and combined stresses of freeze-thaw and cadmium. The results showed that the combined stress severely inhibited shoot length, root length, fresh weight, and dry weight, increased malondialdehyde and hydrogen peroxide contents, and significantly decreased superoxide dismutase (SOD) activity. Foliar application of 5mM GABA alleviated the negative effects of stress on seedling growth, increased soluble protein content, and reduced malondialdehyde and hydrogen peroxide contents. Exogenous GABA application also enhanced the activities of SOD and peroxidase (POD). Additionally, the presence of exogenous GABA activated the GABA metabolic process and encouraged the accumulation of phytochelatins, glutathione, and non-protein thiol. These results indicate that exogenous GABA can effectively improve the resistance of rye seedlings to freeze-thaw and Cd by regulating the antioxidant enzyme system and enhancing its own detoxification mechanism, and they provide a basis for future applications of exogenous GABA, which is beneficial for ecological protection.


Asunto(s)
Cadmio , Congelación , Secale , Plantones , Ácido gamma-Aminobutírico , Secale/efectos de los fármacos , Secale/crecimiento & desarrollo , Ácido gamma-Aminobutírico/metabolismo , Cadmio/toxicidad , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Plantones/metabolismo , Estrés Fisiológico/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Malondialdehído/metabolismo , Peróxido de Hidrógeno/metabolismo
6.
Environ Res ; 263(Pt 3): 120267, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39481783

RESUMEN

Ocean acidification (OA) driven by human activities and climate change presents new challenges to marine ecosystems. At the same time, the risks posed by micro(nano)plastics (MNPs) and engineered nanoparticles (ENPs) to marine ecosystems are receiving increasing attention. Although previous studies have uncovered the environmental behavior and the toxic effects of MNPs and ENPs under OA, there is a lack of comprehensive literature reviews in this field. Therefore, this paper reviews how OA affects the environmental behavior of MNPs and ENPs, and summarizes the effects and the potential mechanisms of their co-exposure on marine organisms. The review indicates that OA changes the marine chemical environment, thereby altering the behavior of MNPs and ENPs. These changes affect their bioavailability and lead to co-exposure effects. This impacts marine organisms' energy metabolism, growth and development, antioxidant systems, reproduction and immunity. The potential mechanisms involved the regulation of signaling pathways, abnormalities in energy metabolism, energy allocation, oxidative stress, decreased enzyme activity, and disruptions in immune and reproductive functions. Finally, based on the limitations of existing research, actual environment and hot issues, we have outlined future research needs and identified key priorities and directions for further investigation. This review deepens our understanding of the potential effects of MNPs and ENPs on marine organisms under OA, while also aiming to promote further research and development in related fields.

7.
Curr Biol ; 34(21): 5040-5053.e6, 2024 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-39419031

RESUMEN

Formin is an important player in promoting apical actin polymerization in pollen tubes, but the mechanism regulating its activity remains unknown. We here identify REN1, a Rho GTPase-activating protein, as a negative regulator of formins in Arabidopsis pollen tubes. Specifically, we found that depletion of REN1 promotes apical actin polymerization and increases the amount of filamentous actin in pollen tubes. Interestingly, the effect of REN1 loss of function phenocopies the effect of formin gain of function, as it causes the formation of supernumerary membrane-derived actin bundles, which leads to tube swelling and membrane deformation. Importantly, inhibition of formins suppresses the phenotypic defects in ren1 mutant pollen tubes. We further demonstrate that REN1 physically interacts with the Arabidopsis formin protein AtFH5, predominantly with the C terminus, and inhibits the ability of AtFH5 to nucleate and assemble actin in vitro. Depletion of AtFH5 partially suppresses the phenotype in ren1 mutant pollen tubes, demonstrating that REN1 regulates apical actin polymerization at least partially through inhibiting AtFH5. We thus uncover a novel mechanism regulating formins and actin polymerization in plants.


Asunto(s)
Actinas , Proteínas de Arabidopsis , Arabidopsis , Tubo Polínico , Polimerizacion , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Tubo Polínico/metabolismo , Tubo Polínico/crecimiento & desarrollo , Actinas/metabolismo , Proteínas Activadoras de GTPasa/metabolismo , Proteínas Activadoras de GTPasa/genética , Forminas/metabolismo , Forminas/genética , Proteínas de Ciclo Celular
8.
Int J Biol Macromol ; 280(Pt 3): 135834, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39307490

RESUMEN

Mannose-binding lectin-associated serine protease 1 (MASP1) plays a crucial role in the complement lectin pathway and the mediation of immune responses. However, comprehensive research on MASP1 across various cancer types has not been performed to date. This study aimed to evaluate the significance of MASP1 in pan-cancer. The Cancer Genome Atlas (TCGA), UCSC Xena and Genotype Tissue Expression (GTEx) databases were used to evaluate the expression profiles, genomic features, prognostic relevance, and immune microenvironment associations of MASP1 across 33 cancer types. We observed significant dysregulation of MASP1 expression in multiple cancers, with strong associations between MASP1 expression levels and diagnostic value as well as patient prognosis. Mechanistic insights revealed significant correlations between MASP1 levels and various immunological and genomic factors, including tumor-infiltrating immune cells (TIICs), immune-related genes, mismatch repair (MMR), tumor mutation burden (TMB), and microsatellite instability (MSI), highlighting a critical regulatory function of MASP1 within the tumor immune microenvironment (TIME). In vitro and in vivo experiments demonstrated that MASP1 expression was markedly decreased in liver hepatocellular carcinoma (LIHC). Moreover, the overexpression of MASP1 in hepatocellular carcinoma (HCC) cell lines significantly inhibited their proliferation, invasion and migration. In conclusion, MASP1 exhibits differential expression in the pan-cancer analyses and might play an important role in TIME. MASP1 is a promising prognostic biomarker and a potential target for immunological research, particularly in LIHC.

9.
Bioact Mater ; 42: 68-84, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39280579

RESUMEN

Biofilm-related biomaterial infections are notoriously challenging to treat and can lead to chronic infection and persisting inflammation. To date, a large body of research can be reviewed for coatings which potentially prevent bacterial infection while promoting implant integration. Yet only a very small number has been translated from bench to bedside. This study provides an in-depth analysis of the stability, antibacterial mechanism, and biocompatibility of medical grade polycaprolactone (mPCL), coated with human serum albumin (HSA), the most abundant protein in blood plasma, and tannic acid (TA), a natural polyphenol with antibacterial properties. Molecular docking studies demonstrated that HSA and TA interact mainly through hydrogen-bonding, ionic and hydrophobic interactions, leading to smooth and regular assemblies. In vitro bacteria adhesion testing showed that coated scaffolds maintained their antimicrobial properties over 3 days by significantly reducing S. aureus colonization and biofilm formation. Notably, amplitude modulation-frequency modulation (AMFM) based viscoelasticity mapping and transmission electron microscopy (TEM) data suggested that HSA/TA-coatings cause morphological and mechanical changes on the outer cell membrane of S. aureus leading to membrane disruption and cell death while proving non-toxic to human primary cells. These results support this antibiotic-free approach as an effective and biocompatible strategy to prevent biofilm-related biomaterial infections.

10.
BMC Palliat Care ; 23(1): 230, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39334204

RESUMEN

BACKGROUND: The transition of family caregivers of patients with end-of-Life cancer receiving palliative care from hospital to home is a complex and challenging process. This phase of care involves not only the physical and psychological health of the patient but also the role adaptation and emotional support of the family caregivers. To gain a deeper understanding of the various experiences and feelings during this process, we conducted a qualitative study. METHODS: This study employed a descriptive phenomenological research method. The interviews focused on the specific experiences, challenges faced, support received, and coping strategies of family caregivers of patients with end-of-life cancer during the transition from hospital to home palliative care. All data were treated with strict confidentiality, and recordings and transcriptions were made with the participants' consent. RESULTS: A total of 15 family caregivers participated. Four main themes and nine sub-themes were identified: complex transition process (anxiety about uncertainty, resistance to transition), discontinuity in care (insufficient discharge guidance, lack of continuous communication mechanisms), post-discharge continuous care needs (need for home care knowledge and skills, social and emotional support, grief counselling and death education), and personal growth and gains (enhanced coping ability, increased psychological resilience). CONCLUSION: Family caregivers face numerous emotional, cognitive, practical, and social support challenges during the transition from hospital to home care. To improve the caregiving experience and quality of life, appropriate training and support should be provided to better meet the caregivers' needs.


Asunto(s)
Adaptación Psicológica , Cuidadores , Servicios de Atención de Salud a Domicilio , Neoplasias , Cuidados Paliativos , Investigación Cualitativa , Humanos , Masculino , Cuidadores/psicología , Femenino , Persona de Mediana Edad , Cuidados Paliativos/métodos , Cuidados Paliativos/psicología , Cuidados Paliativos/normas , Adulto , Anciano , Neoplasias/psicología , Neoplasias/terapia , Servicios de Atención de Salud a Domicilio/normas , Cuidado Terminal/psicología , Cuidado Terminal/métodos , Cuidado Terminal/normas , Apoyo Social
11.
Molecules ; 29(17)2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39274982

RESUMEN

With the increasing global incidence and mortality rates of cancer, the development of novel anti-tumor drugs has become particularly urgent. Scutellaria barbata D. Don, a perennial herb belonging to the genus Scutellaria in the family Lamiaceae, has aroused extensive attention for its medicinal value in recent years. This article presents an exhaustive review of the flavonoid, diterpene, and other chemical constituents harbored within Scutellaria barbata, delving into the intricate mechanisms by which these compounds orchestrate their anti-tumor effects via diverse biological pathways. Remarkably, these compounds distinguish themselves through their capability to regulate cellular signaling, inhibit cancer cell proliferation, trigger apoptosis, disrupt angiogenesis, and bolster immune responses. These anti-tumor effects are achieved through strategic modulation of pivotal signaling cascades, particularly the PI3K/Akt/mTOR, MAPK, and NFκB pathways. In addition, this article also summarizes the clinical applications of Scutellaria barbata in tumor treatment, especially its potential in alleviating the side effects of radiotherapy and chemotherapy and improving patients' quality of life. In conclusion, this review comprehensively summarizes and analyzes the chemical constituents, anti-tumor mechanisms, and clinical applications of Scutellaria barbata, with the aim of systematically reviewing the existing research results and exploring potential future research directions.


Asunto(s)
Antineoplásicos Fitogénicos , Neoplasias , Extractos Vegetales , Scutellaria , Scutellaria/química , Humanos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Neoplasias/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Flavonoides/química , Flavonoides/farmacología , Fitoquímicos/química , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Proliferación Celular/efectos de los fármacos
12.
Small ; : e2403078, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39221641

RESUMEN

Ti3C2Tx (MXene) is widely acknowledged as an excellent substrate for constructing heterogeneous structures with transition metal chalcogenides (TMCs) for boosting the electrochemical performance of lithium-ion storage. However, conventional synthesis strategies inevitably lead to poor electrochemical charge transfer due to Ti3C2Tx-derived TiO2 at the heterogeneous interface between Ti3C2Tx and TMCs. Here, an innovative in situ selenization strategy is proposed to replace the originally generated TiO2 on Ti3C2Tx with metallic TiSe2 interphase, clearing the bottleneck of slow charge transfer barrier caused by MXene oxidation. The construction of bimetallic selenide formed by CoSe2 and TiSe2 generates intrinsic electric fields to guide the fast ion diffusion kinetics in a heterogeneous interface. Additionally, the CoSe2/TiSe2/Ti3C2Tx heterogeneous structure with enhanced structural stability and improved rate performance is confirmed by both experiments and theoretical calculations. The engineered heterogeneous structure exhibits an ultra-high pseudocapacitance contribution (73.1% at 0.1 mV s-1), rendering it well-suited to offset the kinetics differences between double-layer materials. The assembled lithium-ion capacitor based on CoSe2/TiSe2/Ti3C2Tx possesses a high energy density and an ultralong life span (89.5% after 10 000 times at 2 A g-1). This devised strategy provides a feasible solution for utilizing the performance advantages of MXene substrates in lithium storage with ultrafast charge transfer kinetics.

13.
Hum Cell ; 37(6): 1719-1733, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39181971

RESUMEN

Uveal melanoma is a malignant tumor originating from melanocytes in the eye's uvea, often detected during routine ophthalmic examinations due to its typically asymptomatic nature. Despite effective local treatments, up to 50% of patients develop hematogenous metastases, highlighting the need for better prognostic markers and therapeutic targets. In this study, we developed an innovative Metastasis-Related Gene Signature (MERGS) score to classify patients from various cohorts. By establishing this scoring method, we discovered underlying mechanisms responsible for significant differences between samples with high and low MERGS scores. We identified a set of ten genes to construct MERGS, which showed a high predictive accuracy for patient survival. Further, Monoglyceride Lipase (MGLL) emerged as the most important gene in distinguishing uveal melanoma metastasis. Functional studies demonstrated that knocking down MGLL significantly inhibited proliferation, invasion, and migration of uveal melanoma cells in vitro and in vivo, while overexpression of MGLL enhanced these malignant behaviors. Additionally, MGLL modulated free fatty acid (FFA) levels within these cells. Our findings reveal MGLL as a crucial player in uveal melanoma progression and propose it as a novel therapeutic target, potentially leading to improved management and outcomes for patients with this disease.


Asunto(s)
Proliferación Celular , Melanoma , Monoacilglicerol Lipasas , Metástasis de la Neoplasia , Neoplasias de la Úvea , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/patología , Neoplasias de la Úvea/metabolismo , Melanoma/genética , Melanoma/patología , Melanoma/metabolismo , Humanos , Proliferación Celular/genética , Monoacilglicerol Lipasas/genética , Monoacilglicerol Lipasas/metabolismo , Metástasis de la Neoplasia/genética , Ácidos Grasos no Esterificados/metabolismo , Línea Celular Tumoral , Expresión Génica/genética , Movimiento Celular/genética , Invasividad Neoplásica/genética
14.
J Integr Neurosci ; 23(8): 151, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39207071

RESUMEN

BACKGROUND AND PURPOSE: To investigate the abnormal pattern of altered functional activity in the brain and the neuroimaging mechanisms underlying the cognitive impairment of patients with colorectal cancer (CRC) via resting-state functional magnetic resonance imaging (rs-fMRI). MATERIALS AND METHODS: CRC patients (n = 56) and healthy controls (HCs) (n = 50) were studied. The participants underwent rs-fMRI scans and the Montreal Cognitive Assessment (MoCA). The amplitude of low-frequency fluctuations (ALFF), degree centrality (DC), regional homogeneity (ReHo), and MoCA scores, were calculated for participants. RESULTS: The scores of executives, visuospatial, memory, language and attention were lower in CRC patients. ReHo and ALFF values in the left postcentral gyrus, ReHo values in the right postcentral gyrus, ALFF and DC values in the left middle occipital gyrus, ReHo and DC values in the right lingual gyrus, DC values in the right angular gyrus and precuneus, and ALFF values in the left middle temporal gyrus decreased conspicuously in the CRC patients. CONCLUSION: CRC patients have abnormal resting state function, mainly in the brain areas involved in cognitive function. The overlapping brain regions with abnormal functional indicators are in the middle occipital gyrus, postcentral gyrus, and lingual gyrus. This study reveals the potential biological pathways involved in brain impairment and neurocognitive decline in patients with CRC.


Asunto(s)
Disfunción Cognitiva , Neoplasias Colorrectales , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Neoplasias Colorrectales/fisiopatología , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/complicaciones , Persona de Mediana Edad , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Adulto , Anciano , Descanso/fisiología , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Pruebas de Estado Mental y Demencia
15.
Pharmaceutics ; 16(8)2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39204335

RESUMEN

Wound healing progresses through three distinct stages: inflammation, proliferation, and remodeling. Immune regulation is a central component throughout, crucial for orchestrating inflammatory responses, facilitating tissue repair, and restraining scar tissue formation. Elements such as mitochondria, reactive oxygen species (ROS), macrophages, autophagy, ferroptosis, and cytokines collaboratively shape immune regulation in this healing process. Skin wound dressings, recognized for their ability to augment biomaterials' immunomodulatory characteristics via antimicrobial, antioxidative, pro- or anti-inflammatory, and tissue-regenerative capacities, have garnered heightened attention. Notwithstanding, a lack of comprehensive research addressing how these dressings attain immunomodulatory properties and the mechanisms thereof persists. Hence, this paper pioneers a systematic review of biomaterials, emphasizing immune regulation and their underlying immunological mechanisms. It begins by highlighting the importance of immune regulation in wound healing and the peculiarities and obstacles faced in skin injury recovery. This segment explores the impact of wound metabolism, infections, systemic illnesses, and local immobilization on the immune response during healing. Subsequently, the review examines a spectrum of biomaterials utilized in skin wound therapy, including hydrogels, aerogels, electrospun nanofiber membranes, collagen scaffolds, microneedles, sponges, and 3D-printed constructs. It elaborates on the immunomodulatory approaches employed by these materials, focusing on mitochondrial and ROS modulation, autophagic processes, ferroptosis, macrophage modulation, and the influence of cytokines on wound healing. Acknowledging the challenge of antibiotic resistance, the paper also summarizes promising plant-based alternatives for biomaterial integration, including curcumin. In its concluding sections, the review charts recent advancements and prospects in biomaterials that accelerate skin wound healing via immune modulation. This includes exploring mitochondrial transplantation materials, biomaterial morphology optimization, metal ion incorporation, electrostimulation-enabled immune response control, and the benefits of composite materials in immune-regulatory wound dressings. The ultimate objective is to establish a theoretical foundation and guide future investigations in the realm of skin wound healing and related materials science disciplines.

16.
Ther Adv Med Oncol ; 16: 17588359241264727, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39091601

RESUMEN

Background: Several studies have systematically assessed the efficacy and safety of progressive or recurrent glioblastoma multiforme (GBM). However, the discernible limitations of efficacy and the elevated costs of interventions instigate an investigation into the cost-effectiveness of these treatments. Objectives: This study aimed to evaluate cost-effectivenesses of 11 pharmacotherapeutic interventions for recurrent GBM from the perspective of healthcare payers in the United States (US) and China. Design: A model-based pharmacoeconomic evaluation. Methods: A partitioned survival model was employed to evaluate the cost-effectiveness of 11 distinct drug-based treatments. The clinical efficacy and safety data were obtained from a network meta-analysis, while the medical expenditure and health utility were primarily derived from published literature. One-way sensitivity analyses, scenario analyses, and probabilistic sensitivity analyses (PSA) were performed to scrutinize the impact of potential uncertainties to ensure the robustness of the model. The primary endpoint was the incremental cost-effectiveness ratio. Results: Among the therapeutic interventions evaluated, lomustine emerged as the cheapest option, with costs amounting to $78,998 in the United States and $30,231 in China, respectively. Regorafenib displayed the highest quality-adjusted life years at 0.475 in the United States and 0.465 in China. The one-way sensitivity analyses underscored that drug price was a key factor influencing cost-effectiveness. Both scenario and PSA consistently demonstrated that, considering the willingness-to-pay thresholds, lomustine was a cost-effective treatment with probability of more than 94%. Conclusion: In comparison to the alternative antitumor agents, lomustine was likely to be a cost-effective option for relapsed GBM patients from the perspective of healthcare payers in both the United States and China.

17.
Front Pharmacol ; 15: 1436624, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39193331

RESUMEN

Panax ginseng (P. ginseng), a traditional and highly valued botanical drug, has been used for thousands of years and is known around the world for its uses in food, medicine, and healthcare. The comprehensive study of P. ginseng is crucial for the quality assurance of medicinal materials and optimal resource utilization. Despite being present in trace amounts, P. ginseng volatile oil has a wide range of chemical metabolites with important medicinal potential. The volatile oil has shown promise in defending the cardiovascular system, as well as in terms of its ability of antibacterial, anti-aging, anti-platelet coagulation, anti-inflammatory, support the nervous system nutritionally, and shield it from harm. Due to its low composition and lack of thorough investigation, P. ginseng volatile oil's therapeutic applicability is still restricted although it exhibited many benefits. This review aims to provide insights into the chemical composition, extraction processes, pharmacological effects, and mechanisms of action of P. ginseng volatile oil, and to provide theoretical support and guidelines for future research and clinical application.

18.
Natl Sci Rev ; 11(8): nwae199, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39050980

RESUMEN

Rechargeable aqueous Zn-ion batteries have been deemed a promising energy storage device. However, the dendrite growth and side reactions have hindered their practical application. Herein, inspired by the ultrafluidic and K+ ion-sieving flux through enzyme-gated potassium channels (KcsA) in biological plasma membranes, a metal-organic-framework (MOF-5) grafted with -ClO4 groups (MOF-ClO4) as functional enzymes is fabricated to mimic the ultrafluidic lipid-bilayer structure for gating Zn2+ 'on' and anions 'off' states. The MOF-ClO4 achieved perfect Zn2+/SO4 2- selectivity (∼10), enhanced Zn2+ transfer number ([Formula: see text]) and the ultrafluidic Zn2+ flux (1.9 × 10-3 vs. 1.67 mmol m-2 s-1 for KcsA). The symmetric cells based on MOF-ClO4 achieve a lifespan of over 5400 h at 10 mA cm-2/20 mAh cm-2. Specifically, the performance of the PMCl-Zn//V2O5 pouch cell keeps 81% capacity after 2000 cycles at 1 A g-1. The regulated ion transport, by learning from a biological plasma membrane, opens a new avenue towards ultralong lifespan aqueous batteries.

19.
Am J Reprod Immunol ; 92(1): e13893, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38958245

RESUMEN

PROBLEM: Vulvovaginal candidiasis (VVC) is a common mucosal fungal infection, and Candida albicans is the main causative agent. The NLRP3 inflammasome plays an important role in VVC, but the underlying mechanism is unknown. METHOD OF STUDY: Vaginal epithelial cells were divided into three groups: control, C. albicans strain SC5314 (wild-type, WT), and WT+ Matt Cooper Compound 950 (MCC950, a specific NLRP3 inhibitor). After human vaginal epithelial cells were pretreated with 1 µmol/L MCC950 for 2 h, C. albicans (MOI = 1) was cocultured with the human vaginal epithelial cells for 12 h. The cell supernatants were collected, LDH was detected, and the IL-1ß and IL-18 levels were determined by ELISA. The expression of the pyroptosis-related proteins NLRP3, Caspase-1 p20 and GSDMD was measured by Western blotting analysis. The protein expression of the pyroptosis-related N-terminus of GSDMD (GSDMD-N) was detected by immunofluorescence. RESULTS: In this study, we showed that the WT C. albicans strain induced pyroptosis in vaginal epithelial cells, as indicated by the LDH and proinflammatory cytokine levels and the upregulated levels of the pyroptosis-related proteins NLRP3, Caspase-1 p20, and GSDMD-N. MCC950 reversed the changes in the expression of these proteins and proinflammatory cytokines in vaginal epithelial cells. CONCLUSION: C. albicans activated the NLRP3 inflammasome to induce vaginal epithelial cell pyroptosis. MCC950 inhibited the NLRP3 inflammasome, reduced vaginal epithelial cell pyroptosis, and decreased the release of inflammatory cytokines.


Asunto(s)
Candida albicans , Candidiasis Vulvovaginal , Células Epiteliales , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Vagina , Femenino , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Candidiasis Vulvovaginal/inmunología , Candidiasis Vulvovaginal/microbiología , Candidiasis Vulvovaginal/metabolismo , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Inflamasomas/metabolismo , Inflamasomas/inmunología , Candida albicans/inmunología , Vagina/microbiología , Vagina/inmunología , Vagina/patología , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Indenos , Furanos/farmacología , Caspasa 1/metabolismo , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Proteínas de Unión a Fosfato/metabolismo , Células Cultivadas , Sulfonamidas
20.
mBio ; 15(8): e0061924, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39012150

RESUMEN

Plant bacterial wilt caused by Ralstonia solanacearum results in huge losses. Accordingly, developing an effective control method for this disease is urgently required. Filamentous phages, which do not lyse host bacteria and exert minimal burden, offer a potential biocontrol solution. A filamentous phage RSCq that infects R. solanacearum was isolated in this study through genome mining. We constructed engineered filamentous phages based on RSCq by employing our proposed approach with wide applicability to non-model phages, enabling the exogenous genes delivery into bacterial cells. CRISPR-AsCas12f1 is a miniature class 2 type V-F CRISPR-Cas system. A CRISPR-AsCas12f1-based gene editing system that targets the key virulence regulator gene hrpB was developed, generating the engineered phage RSCqCRISPR-Cas. Similar to the Greek soldiers in the Trojan Horse, our findings demonstrated that the engineered phage-delivered CRISPR-Cas system could disarm the key "weapon," hrpB, of R. solanacearum, in medium and plants. Remarkably, pretreatment with RSCqCRISPR-Cas significantly controlled tobacco bacterial wilt, highlighting the potential of engineered filamentous phages as promising biocontrol agents against plant bacterial diseases.IMPORTANCEBacterial disease, one of the major plant diseases, causes huge food and economic losses. Phage therapy, an environmentally friendly control strategy, has been frequently reported in plant bacterial disease control. However, host specificity, sensitivity to ultraviolet light and certain conditions, and bacterial resistance to phage impede the widespread application of phage therapy in crop production. Filamentous phages, which do not lyse host bacteria and exert minimal burden, offer a potential solution to overcome the limitations of lytic phage biocontrol. This study developed a genetic engineering approach with wide applicability to non-model filamentous phages and proved the application possibility of engineered phage-based gene delivery in plant bacterial disease biocontrol for the first.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Enfermedades de las Plantas , Ralstonia solanacearum , Ralstonia solanacearum/genética , Ralstonia solanacearum/virología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Edición Génica/métodos , Inovirus/genética , Inovirus/fisiología , Nicotiana/microbiología
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