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Diabetic foot ulcers (DFUs) are a serious vascular disease. Currently, no effective methods are available for treating DFUs. Pro-protein convertase subtilisin/kexin type 9 (PCSK9) regulates lipid levels to promote atherosclerosis. However, the role of PCSK9 in DFUs remains unclear. In this study, we found that the expression of PCSK9 in endothelial cells (ECs) increased significantly under high glucose (HG) stimulation and in diabetic plasma and vessels. Specifically, PCSK9 promotes the E3 ubiquitin-protein ligase NEDD4 binding to vascular endothelial growth factor receptor 2 (VEGFR2), which led to the ubiquitination of VEGFR2, resulting in its degradation and downregulation in ECs. Furthermore, PCSK9 suppresses the expression and activation of AKT, endothelial nitric oxide synthase (eNOS), and ERK1/2, leading to decreased nitric oxide (NO) production and increased superoxide anion (O2._) generation, which impairs vascular endothelial function and angiogenesis. Importantly, using evolocumab to limit the increase in PCSK9 expression blocked the HG-induced inhibition of NO production and the increase in O2._ production, as well as inhibited the phosphorylation and expression of AKT, eNOS, and ERK1/2. Moreover, evolocumab improved vascular endothelial function and angiogenesis, and promoted wound healing in diabetes. Our findings suggest that targeting PCSK9 is a novel therapeutic approach for treating DFUs.
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The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 system, a groundbreaking innovation in genetic engineering, has revolutionized our approach to surmounting complex diseases, culminating in CASGEVY™ approved for sickle cell anemia. Derived from a microbial immune defense mechanism, CRISPR/Cas9, characterized as precision, maneuverability and universality in gene editing, has been harnessed as a versatile tool for precisely manipulating DNA in mammals. In the process of applying it to practice, the consecutive exploitation of novel orthologs and variants never ceases. It's conducive to understanding the essentialities of diseases, particularly cancer, which is crucial for diagnosis, prevention, and treatment. CRISPR/Cas9 is used not only to investigate tumorous genes functioning but also to model disparate cancers, providing valuable insights into tumor biology, resistance, and immune evasion. Upon cancer therapy, CRISPR/Cas9 is instrumental in developing individual and precise cancer therapies that can selectively activate or deactivate genes within tumor cells, aiming to cripple tumor growth and invasion and sensitize cancer cells to treatments. Furthermore, it facilitates the development of innovative treatments, enhancing the targeting efficiency of reprogrammed immune cells, exemplified by advancements in CAR-T regimen. Beyond therapy, it is a potent tool for screening susceptible genes, offering the possibility of intervening before the tumor initiative or progresses. However, despite its vast potential, the application of CRISPR/Cas9 in cancer research and therapy is accompanied by significant efficacy, efficiency, technical, and safety considerations. Escalating technology innovations are warranted to address these issues. The CRISPR/Cas9 system is revolutionizing cancer research and treatment, opening up new avenues for advancements in our understanding and management of cancers. The integration of this evolving technology into clinical practice promises a new era of precision oncology, with targeted, personalized, and potentially curative therapies for cancer patients.
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Sistemas CRISPR-Cas , Neoplasias , Medicina de Precisión , Humanos , Sistemas CRISPR-Cas/genética , Medicina de Precisión/métodos , Neoplasias/genética , Neoplasias/terapia , Edición Génica/métodos , Animales , Oncología Médica/métodos , Oncología Médica/tendenciasRESUMEN
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by abnormal protein deposition. With an alarming 30 million people affected worldwide, AD poses a significant public health concern. While inhibiting key enzymes such as ß-site amyloid precursor protein-cleaving enzyme 1 and γ-secretase or enhancing amyloid-ß clearance, has been considered the reasonable strategy for AD treatment, their efficacy has been compromised by ineffectiveness. Furthermore, our understanding of AD pathogenesis remains incomplete. Normal aging is associated with a decline in glucose uptake in the brain, a process exacerbated in patients with AD, leading to significant impairment of a critical post-translational modification: glycosylation. Glycosylation, a finely regulated mechanism of intracellular secondary protein processing, plays a pivotal role in regulating essential functions such as synaptogenesis, neurogenesis, axon guidance, as well as learning and memory within the central nervous system. Advanced glycomic analysis has unveiled that abnormal glycosylation of key AD-related proteins closely correlates with the onset and progression of the disease. In this context, we aimed to delve into the intricate role and underlying mechanisms of glycosylation in the etiopathology and pathogenesis of AD. By highlighting the potential of targeting glycosylation as a promising and alternative therapeutic avenue for managing AD, we strive to contribute to the advancement of treatment strategies for this debilitating condition.
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Shift work is a recognized work pattern for nurses worldwide. The disruption of shift workers' biological clocks usually leads to sleep disorders and affects their awareness at work. Eveningness and occupational stress might be effective in causing burnout syndrome. Therefore, this study aimed to evaluate the chronotype, job burnout and perceived stress among Chinese tertiary hospital nurses, and understand the predictors of circadian rhythm in this group. Between July and September 2020, 23 hospitals were randomly selected from 113 tertiary hospitals in Hunan Province. Twenty-five percent of the nurses working in each hospital were targeted for selection. 28.1% and 17.6% of nurses reported eveningness type and morningness type, respectively. The scores for emotional exhaustion, depersonalization, and perceived stress of eveningness nurses were higher than those of morningness counterparts. Eveningness nurses also reported a lower sense of personal accomplishment. Risk factors of eveningness included being under 30 years old, never exercising, having the stressors of late-night shifts and career development, higher levels of emotional exhaustion, sleep latency, sleep duration, and hypnotic use. Shifts may be unavoidable for nurses, nevertheless, understanding the predictors and related factors of chronotype for nurses is necessary for nursing educators and managers to develop a reasonable shift system and appropriate measures to assist nurses in adjusting their work.
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Agotamiento Profesional , Cronotipo , Enfermeras y Enfermeros , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , China/epidemiología , Estudios Transversales , Pueblos del Este de Asia , Personal de Enfermería en Hospital/psicología , Estrés Laboral , Factores de Riesgo , Horario de Trabajo por Turnos , Sueño/fisiología , Encuestas y Cuestionarios , Centros de Atención Terciaria , Tolerancia al Trabajo ProgramadoRESUMEN
PURPOSE: Adolescent and young adult (AYA) cancer patients, aged between 15 to 39 years old, suffer from long-term psychological distress, confronting low self-efficacy and various psychological problems. This study constructs a group online-based peer support intervention combined with offline activities to explore its impact on the psychological distress of AYA cancer patients. METHODS: A randomized, two-arm clinical trial was conducted in which 90 AYA cancer patients were recruited. The control group (N = 45) received conventional psychological care and treatment, and the experimental group (N = 45) received 8 weeks of an online peer support intervention. Outcome measures included psychological distress (Distress Thermometer, DT), anxiety and depression (Hospital Anxiety and Depression Scale, HADS), perceived peer support (Cancer Peer Support Scales, CaPSS), and readiness for return to work (Readiness to Return-To-Work Scale, RRTW). RESULTS: Eight-week peer support intervention was effective in improving psychological distress, anxiety, and depressive symptoms in the experimental group with statistically significant differences (P < 0.05). Time affected psychological distress, anxiety, and depressive symptoms in AYA cancer patients (P < 0.05), and there was an interaction with intervention factors (P < 0.05). The intervention has a positive effect on relieving the psychological status of AYA cancer patients. For readiness for return to work, the experimental group was in the preparation for the action-behavioral stage immediately, 1 month and 3 months after the end of the intervention (P < 0.01), supporting AYA cancer patients who have not returned to work to maintain optimal return-to-work readiness. CONCLUSIONS: The group online-based peer support intervention is popular and has good scientificity, effectiveness, and practical significance for AYA cancer patients. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov. (ChiCTR2100053091, registered on 10 November 2021).
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Neoplasias , Grupo Paritario , Distrés Psicológico , Apoyo Social , Humanos , Adolescente , Femenino , Masculino , Adulto Joven , Adulto , Neoplasias/psicología , Neoplasias/terapia , Depresión/terapia , Depresión/etiología , Depresión/psicología , Ansiedad/etiología , Ansiedad/terapia , Estrés Psicológico/etiología , Estrés Psicológico/terapia , Intervención basada en la InternetRESUMEN
Lung metastasis of breast cancer is rapidly becoming a thorny problem in the treatment of patients with breast cancer and an obstacle to long-term survival. The main challenges of treatment are the absence of therapeutic targets and drug resistance, which promotes the development of nanotechnology in the diagnosis and treatment process. Taking advantage of the controllability and targeting of nanotechnology, drug-targeted delivery, controlled sustained release, multi-drug combination, improved drug efficacy, and reduced side effects can be realized in the process of the diagnosis and treatment of metastatic breast cancer (MBC). Several nanotechnology-based theranostic strategies have been investigated in breast cancer lung metastases (BCLM): targeted drug delivery, imaging analysis, immunotherapy, gene therapy, and multi-modality combined therapy, and some clinical applications are in the research phase. In this review, we present current nanotechnology-based diagnosis and treatment approaches for patients of incurable breast cancer with lung metastases, and we hope to be able to summarize more effective and promising nano-drug diagnosis and treatment systems that aim to improve the survival of patients with advanced MBC. We describe nanoplatform-based experimental studies and clinical trials targeting the tumor and the tumor microenvironment (TME) for BCLM to obtain more targeted treatment and in the future treatment steps for patients to provide a pioneering strategy.
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As one of the nine primary non-ferrous metal smelting bases in China, Daye Lake basin was polluted due to diverse human activities. But so far the pollution status and related ecological risks of this region have not been detailly investigated. In current study, pollutants including heavy metals, polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs) in eight sediment samples from Daye Lake were quantified. 18S rRNA gene sequencing was employed to profile the nematode community structure within these sediments. Model organism Caenorhabditis elegans (C. elegans) were further applied for a comprehensive ecological risk assessment of Daye Lake. Notably, Cadmium (Cd) was identified as a key driver of ecological risk, reaching an index of 1287.35. At sample point S4, OCPs particularly p,p'-DDT, displayed an extreme ecological risk with a value of 23.19. Cephalobidae and Mononchida showed strong sensitivity to pollutant levels, reinforcing their suitability as robust bioindicators. The composite pollutants in sampled sediments caused oxidative stress in C. elegans, with gene Vit-2 and Mtl-1 as sensitive biomarkers. By employing the multiple analysis methods, our data can offer valuable contributions to environmental monitoring and health risk assessment for composite polluted areas.
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Monitoreo del Ambiente , Hidrocarburos Clorados , Lagos , Metales Pesados , Contaminantes Químicos del Agua , Lagos/química , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente/métodos , China , Animales , Hidrocarburos Clorados/análisis , Medición de Riesgo , Metales Pesados/análisis , Caenorhabditis elegans/efectos de los fármacos , Hidrocarburos Policíclicos Aromáticos/análisis , Sedimentos Geológicos/química , Plaguicidas/análisisRESUMEN
The precise features of lesions in non-ST-segment elevation myocardial infarction (NSTEMI) patients with total occlusion (TO) of the infarct-related artery (IRA) are still unclear. This study employs optical coherence tomography (OCT) to investigate pathological features in NSTEMI patients with or without IRA TO and explores the relationship between thrombus types and IRA occlusive status. This was a single-center retrospective study. A total of 202 patients diagnosed with NSTEMI were divided into two groups: those with Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 before percutaneous coronary intervention (PCI) (referred to as the TO group, n = 100) and those TIMI flow grade 1-3 (referred to as the Non-TO group, n = 102). Baseline characteristics, coronary angiography findings, and OCT results were collected. Multivariate logistic analysis identified factors influencing TO in NSTEMI. The category of NSTEMI was further subdivided based on the type of electrocardiogram (ECG) into two subgroups: ST segment unoffset myocardial infarction (STUMI) and ST segment depression myocardial infarction (STDMI). This division allows for a more specific classification of NSTEMI cases. The TO group had a younger age, higher male representation, more smokers, lower hypertension and cerebrovascular disease incidence, lower left ventricular ejection fraction (LVEF), and higher creatine kinase myocardial band (CKMB) and creatine kinase (CK) peak levels. In the TO group, LCX served as the main IRA (52.0%), whereas in the Non-TO group, LAD was the predominant IRA (45.1%). Compared to the Non-TO group, OCT findings demonstrated that red thrombus/mixed thrombus was more common in the TO group, along with a lower occurrence of white thrombus (p < 0.001). The TO group exhibited a higher prevalence of STUMI (p = 0.001), whereas STDMI was more commonly observed in the Non-TO group (p = 0.001). NSTEMI presents as STUMI and STDMI distinct entities. Red thrombus/mixed thrombus in IRA often indicates occlusive lesions with STUMI on ECG. White thrombus suggests non-occlusive lesions with STDMI on ECG.
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Angiografía Coronaria , Trombosis Coronaria , Vasos Coronarios , Electrocardiografía , Infarto del Miocardio sin Elevación del ST , Intervención Coronaria Percutánea , Valor Predictivo de las Pruebas , Tomografía de Coherencia Óptica , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Infarto del Miocardio sin Elevación del ST/diagnóstico por imagen , Infarto del Miocardio sin Elevación del ST/terapia , Anciano , Trombosis Coronaria/diagnóstico por imagen , Trombosis Coronaria/patología , Factores de Riesgo , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Análisis Multivariante , Modelos Logísticos , Oclusión Coronaria/diagnóstico por imagen , Oclusión Coronaria/fisiopatología , Circulación Coronaria , Distribución de Chi-Cuadrado , Oportunidad RelativaRESUMEN
We studied the regulation dynamics of cerebral blood velocity (CBv) at middle cerebral arteries (MCA) in response to spontaneous changes of arterial blood pressure (ABP), termed dynamic cerebral autoregulation (dCA), and end-tidal CO2 as proxy for blood CO2 tension, termed dynamic vasomotor reactivity (DVR), by analyzing time-series data collected at supine rest from 36 patients with Type-2 Diabetes Mellitus (T2DM) and 22 age/sex-matched non-diabetic controls without arterial hypertension. Our analysis employed a robust dynamic modeling methodology that utilizes Principal Dynamic Modes (PDM) to estimate subject-specific dynamic transformations of spontaneous changes in ABP and end-tidal CO2 (viewed as two "inputs") into changes of CBv at MCA measured via Transcranial Doppler ultrasound (viewed as the "output"). The quantitative results of PDM analysis indicate significant alterations in T2DM of both DVR and dCA in terms of two specific PDM contributions that rise to significance (p < 0.05). Our results further suggest that the observed DVR and dCA alterations may be due to reduction of cholinergic activity (based on previously published results from cholinergic blockade data) that may disturb the sympatho-vagal balance in T2DM. Combination of these two model-based "physio-markers" differentiated T2DM patients from controls (p = 0.0007), indicating diabetes-related alteration of cerebrovascular regulation, with possible diagnostic implications.
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This study aims to investigate the mechanism of platelet activation-induced thrombosis in patients with acute non-ST segment elevation myocardial infarction (NSTEMI) by detecting the expression of autophagy-associated proteins in platelets of patients with NSTEMI. A prospective study was conducted on 121 patients with NSTEMI who underwent emergency coronary angiography and optical coherence tomography. The participants were divided into two groups: the ST segment un-offset group (n = 64) and the ST segment depression group (n = 57). We selected a control group of 60 patients without AMI during the same period. The levels of autophagy-associated proteins and the expression of autophagy-associated proteins in platelets were measured using immunofluorescence staining and Western blot. In NSTEMI, the prevalence of red thrombus was higher in the ST segment un-offset myocardial infarction (STUMI) group, whereas white thrombus was more common in the ST segment depression myocardial infarction (STDMI) group. Furthermore, the platelet aggregation rate was significantly higher in the white thrombus group compared with the red thrombus group. Compared with the control group, the autophagy-related protein expression decreased, and the expression of αIIbß3 increased in NSTEMI. The overexpression of Beclin1 could activate platelet autophagy and inhibit the expression of αIIbß3. The results suggested that the increase in platelet aggregation rate in patients with NSTEMI may be potentially related to the change in autophagy. And the overexpression of Beclin1 could reduce the platelet aggregation rate by activating platelet autophagy. Our findings demonstrated that Beclin1 could be a potential therapeutic target for inhibiting platelet aggregation in NSTEMI.
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Autofagia , Beclina-1 , Plaquetas , Infarto del Miocardio sin Elevación del ST , Activación Plaquetaria , Trombosis , Humanos , Beclina-1/metabolismo , Masculino , Femenino , Infarto del Miocardio sin Elevación del ST/sangre , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Plaquetas/metabolismo , Trombosis/sangre , Trombosis/metabolismo , Angiografía Coronaria , Agregación Plaquetaria , Estudios de Casos y Controles , Tomografía de Coherencia Óptica , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismoRESUMEN
This study explores the potential for optimizing a sustainable manufacturing process that maintains the essential characteristics of conventional liposomes using food-grade solvents and components. The focus was comparing the physicochemical, morphological, and interfacial properties of liposomes produced with these food-grade ingredients to those made by conventional methods. It was found that there was no significant difference in particle size (195.87 ± 1.40 nm) and ζ-potential (-45.13 ± 0.65 mV) between liposomes made from food-grade and conventional materials. The manufacturing process for liposomes, utilizing food-grade solvents and components, was optimized through the application of Plackett-Burman design and response surface methodology. This approach helped identify key parameters (soy lecithin, ß-sitosterol, W/O ratio) and their optimal values (3.17 g, 0.25 g, 1:2.59). These findings suggest that it is possible to enhance the use of liposomes as an effective and safe delivery system in the food industry, adhering to the strict guidelines set by regulatory agencies.
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Lecitinas , Liposomas , Tamaño de la Partícula , Liposomas/química , Lecitinas/química , Sitoesteroles/química , Microfluídica/instrumentación , Glycine max/químicaRESUMEN
Single-cell RNA sequencing (scRNA-seq) facilitates the study of cell type heterogeneity and the construction of cell atlas. However, due to its limitations, many genes may be detected to have zero expressions, i.e. dropout events, leading to bias in downstream analyses and hindering the identification and characterization of cell types and cell functions. Although many imputation methods have been developed, their performances are generally lower than expected across different kinds and dimensions of data and application scenarios. Therefore, developing an accurate and robust single-cell gene expression data imputation method is still essential. Considering to maintain the original cell-cell and gene-gene correlations and leverage bulk RNA sequencing (bulk RNA-seq) data information, we propose scINRB, a single-cell gene expression imputation method with network regularization and bulk RNA-seq data. scINRB adopts network-regularized non-negative matrix factorization to ensure that the imputed data maintains the cell-cell and gene-gene similarities and also approaches the gene average expression calculated from bulk RNA-seq data. To evaluate the performance, we test scINRB on simulated and experimental datasets and compare it with other commonly used imputation methods. The results show that scINRB recovers gene expression accurately even in the case of high dropout rates and dimensions, preserves cell-cell and gene-gene similarities and improves various downstream analyses including visualization, clustering and trajectory inference.
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Algoritmos , Análisis de la Célula Individual , RNA-Seq , Análisis de la Célula Individual/métodos , Análisis de Secuencia de ARN/métodos , Análisis por Conglomerados , Expresión Génica , Perfilación de la Expresión Génica , Programas InformáticosRESUMEN
In this study, a novel human-size handheld magnetic particle imaging (MPI) system was developed for the high-precision detection of sentinel lymph nodes for breast cancer. The system consisted of a highly sensitive home-made MPI detection probe, a set of concentric coils pair for spatialization, a solenoid coil for uniform excitation at 8 kHz@1.5 mT, and a full mirrored coil set positioned far away from the scanning area. The mirrored coils formed an extremely effective differential pickup structure which suppressed the system noise as high as 100 dB. The different combination of the inner and outer gradient current made the field free point (FFP) move in the Z direction with a uniform intensity of 0.54T/m, while the scanning in the XY direction was implemented mechanically. The third-harmonic signal of the Superparamagnetic Iron Oxide Nanoparticles (SPIONs) at the FFP was detected and then reconstructed synchronously with the current changes. Experiment results showed that the tomographic detection limit was 30 mm in the Z direction, and the sensitivity was about 10 µg Fe SPIONs at 40 mm distance with a spatial resolution of about 5 mm. In the rat experiment, 54 µg intramuscular injected SPIONs were detected successfully in the sentinel lymph node, in which the tracer content was about 1.2% total injected Fe. Additionally, the effective detection time window was confirmed from 4 to 6 min after injection. Relevant clinical ethics are already in the application process. Large mammalian SLNB MPI experiments and 3D preoperative SLNB imaging will be performed in the future.
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OBJECTIVES: Depressive symptoms have a considerable negative impact on mental health. This study aimed to understand the relationship between the protein-enriched and anti-inflammatory dietary index scores, modified healthy lifestyle index scores (Modified HLIS), and depressive symptoms. METHODS: This study used convenience sampling to conduct a single-center cross-sectional survey. From January 1, 2015 to December 31, 2020, a total of 287,945 Chinese adults from a health management center of a general hospital completed an online self-reported health questionnaire, which included demographic characteristics, the Dietary Diversity Scale, the Modified Healthy Lifestyle Index Scores and the Patient Health Questionnaire-9. RESULTS: The higher anti-inflammatory dietary index scores (POR = 0.87; 95 % CI: 0.86-0.87; p < 0.001), moderate modified healthy lifestyle index scores (POR = 0.76; 95 % CI: 0.75-0.78; p < 0.001) and sufficient modified healthy lifestyle index scores (POR = 0.53; 95 % CI: 0.52-0.54; p < 0.001) were negatively associated with depressive symptoms, while the higher protein-enriched dietary index scores (POR = 1.01; 95 % CI: 1.01-1.02; p < 0.001) was positively correlated with depressive symptoms. CONCLUSIONS: This study demonstrated that protein-enriched and anti-inflammatory dietary index scores, and multiple healthy lifestyles are associated depressive symptoms in adults.
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Depresión , Patrones Dietéticos , Adulto , Humanos , Estudios Transversales , Depresión/epidemiología , China , Estilo de Vida Saludable , AntiinflamatoriosRESUMEN
Florfenicol (FLO) is a widely used antibacterial drug, which is often detected in the environment. In this paper, the photolysis mechanism of FLO in water was investigated using density functional theory (DFT) and time-dependent density functional theory (TDDFT). The focus of the study is to elucidate the direct photolysis mechanism of FLO in the water environment and the indirect photolysis of free radicals (·OH, ·NO3, and ·SO4-) as active species. The effect of metal ions Ca2+/Mg2+/Zn2+ on the indirect photolysis was also investigated. The results show that the direct photolysis of FLO involves C-C/C-N/C-S bond cleavage, the C5-S7 bond cleavage is most likely to occur, and the C17-C18 cleavage reaction is not easy to occur during the direct photodegradation of FLO. The indirect photolysis of FLO is more likely to occur in the environment than direct photolysis. The main indirect photolysis involves OH-addition, NO3-addition, and SO4-addition on benzene ring. The order of difficulty in the indirect photolysis with ·OH is C2 > C3 > C4 > C5 > C6 > C1, Ca2+ can promote the indirect photolysis with ·OH, and Mg2+/Zn2+ has a dual effect on the indirect photolysis with ·OH. In other words, Mg2+ and Zn2+ can inhibit or promote the indirect photolysis with ·OH. These studies provide important information for theoretical research on the environmental behavior and degradation mechanism of drug molecules.
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Despite standard hormonal therapy that targets the androgen receptor (AR) attenuates prostate cancer (PCa) effectively in the initial stage, the tumor ultimately converts to castration-resistant prostate cancer (CRPC), and the acquired resistance is still a great challenge for the management of advanced prostate cancer patients. The tumor microenvironment (TME) consists of multiple cellular and noncellular agents is well known as a vital role during the development and progression of CRPC by establishing communication between TME and tumor cells. Additionally, as primary prostate cancer progresses towards metastasis, and CRPC always experiences bone metastasis, the TME is conducive to the spread of tumors to the distant sits, particularly in bone. In addition, the bone microenvironment (BME) is also closely related to the survival, growth and colonization of metastatic tumor cells. The present review summarized the recent studies which mainly focused on the role of TME or BME in the CRPC patients with bone metastasis, and discussed the underlying mechanisms, as well as the potential therapeutic values of targeting TME and BME in the management of metastatic CRPC patients.
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Neoplasias Óseas , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias Óseas/tratamiento farmacológico , Microambiente TumoralRESUMEN
In this work, novel lignin-based nanoparticles (LßNPs) with high acidic tolerance were successfully prepared via electrostatic interaction between ß-alanine and lignin nanoparticles. The effects of the mass ratio of lignin nanoparticles to ß-alanine and pH value on the morphology and particle sizes of LßNPs were investigated with the aim of obtaining the ideal nanoparticles. The optimized LßNPs were spherical in shape with an average particle size of 41.1 ± 14.5 nm and exhibited outstanding structure stability under high acidic conditions (pH < 4). Subsequently, Pickering emulsions stabilized by LßNPs were prepared using olive oil as the oil phase. Additionally, the effects of pH value, droplet size, morphology, and storage stability on Pickering emulsions were also analyzed. The emulsions displayed excellent stability, and were stable against strongly acidic conditions (pH < 4) after 30 days of storage. The study presented a promising approach to preparing lignin-based nanoparticles with high acidic tolerance (an ideal type of stabilizer to prepare emulsions), and exhibited extremely high potential application values in the fields of drug delivery, food additives, and oily wastewater treatment.