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RATIONALE AND OBJECTIVES: Prior to clinical presentations of Alzheimer's Disease (AD), neuropathological changes, such as amyloid-ß and brain atrophy, have accumulated at the earlier stages of the disease. The combination of such biomarkers assessed by multiple modalities commonly improves the likelihood of AD etiology. We aimed to explore the discriminative ability of Aß PET features and whether combining Aß PET and structural MRI features can improve the classification performance of the machine learning model in older healthy control (OHC) and mild cognitive impairment (MCI) from AD. MATERIAL AND METHODS: We collected 94 AD patients, 82 MCI patients, and 85 OHC from three different cohorts. 17 global/regional Aß features in Centiloid, 122 regional volume, and 68 regional cortical thickness were extracted as imaging features. Single or combined modality features were used to train the random forest model on the testing set. The top 10 features were sorted based on the Gini index in each binary classification. RESULTS: The results showed that AUC scores were 0.81/0.86 and 0.69/0.68 using sMRI/Aß PET features on the testing set in differentiating OHC and MCI from AD. The performance was improved while combining two-modality features with an AUC of 0.89 and an AUC of 0.71 in two classifications. Compared to sMRI features, particular Aß PET features contributed more to differentiating AD from others. CONCLUSION: Our study demonstrated the discriminative ability of Aß PET features in differentiating AD from OHC and MCI. A combination of Aß PET and structural MRI features can improve the RF model performance.
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BACKGROUND: Circadian rhythm (CR) disturbance is intricately associated with Parkinson's disease (PD). However, the involvement of CR-related mechanisms in the pathogenesis and progression of PD remains elusive. METHODS: A total of 141 PD patients and 113 healthy participants completed CR-related clinical examinations in this study. To further investigate the CR-related mechanisms in PD, we obtained datasets (GSE7621, GSE20141, GSE20292) from the Gene Expression Omnibus database to identify differentially expressed genes between PD patients and healthy controls and further selected CR-related genes (CRRGs). Subsequently, the least absolute shrinkage and selection operator (LASSO) followed by logistic algorithms were employed to identify the hub genes and construct a diagnostic model. The predictive performance was evaluated by area under the curve (AUC), calibration curve, and decision curve analyses in the training set and external validation sets. Finally, RTâqPCR and Western blotting were conducted to verify the expression of these hub genes in blood samples. In addition, Pearson correlation analysis was utilized to validate the association between expression of hub genes and circadian rhythm function. RESULTS: Our clinical observational study revealed that even early-stage PD patients exhibited a higher likelihood of experiencing sleep disturbances, nocturnal hypertension, reverse-dipper blood pressure, and reduced heart rate variability compared to healthy controls. Furthermore, 4 CR-related hub genes (AGTR1, CALR, BRM14, and XPA) were identified and subsequently incorporated as candidate biomarkers to construct a diagnostic model. The model showed satisfactory diagnostic performance in the training set (AUC = 0.941), an external validation set GSE20295 (AUC = 0.842), and our clinical centre set (AUC = 0.805). Additionally, the up-regulation of CALR, BRM14 and the down-regulation of AGTR1, XPA were associated with circadian rhythm disruption. CONCLUSION: CR disturbance seems to occur in the early stage of PD. The diagnostic model based on CR-related genes demonstrated robust diagnostic efficacy, offering novel insights for future clinical diagnosis of PD and providing a foundation for further exploration into the role of CR-related mechanisms in the progression of PD.
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Ritmo Circadiano , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/fisiopatología , Ritmo Circadiano/genética , Masculino , Femenino , Persona de Mediana Edad , Estudios de Casos y Controles , Anciano , Curva ROC , Regulación de la Expresión Génica , Perfilación de la Expresión Génica , Modelos Biológicos , Bases de Datos GenéticasRESUMEN
Anthocyanin (ACN) has attracted considerable attention due to its wide range of physiological effects. However, challenges such as poor stability and limited bioavailability have hindered its utilization in functional foods. To address these issues, this research utilized milk-derived extracellular vesicles (MEV) as carriers for encapsulating and binding ACN through various techniques, including ultrasonic, electroporation, saponin treatment, incubation, and freeze-thaw cycles. The objective of these approaches was to enhance the stability of ACN and improve its oral delivery. Notably, the ACN-loaded MEV (MEV-ACN) prepared through ultrasonic exhibited small particle sizes and good stability under processing, storage, and simulated digestion conditions. Cellular studies revealed that MEV-ACN exhibited pro-oxidant properties and induced oxidative stress, leading to cell apoptosis with greater efficacy compared to free ACN. These findings suggest that encapsulating ACN within MEV can significantly enhance its processing and oral stability, as well as strengthening its dietary defense capabilities in anti-tumor applications.
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Microplastics (MPs) have become an environmental and health threat to aquatic species and humans because they are small and can easily reach water bodies for municipal and agricultural uses. MPs have been traced in food commodities and products derived from animals and even found in bottles of drinking water. Current treatment techniques for permanently destroying MPs require high energy inputs and thus are generally cost-inefficient. Atmospheric cold plasma (ACP) is a low-cost energy-efficient technology to produce highly reactive species that can induce physicochemical changes in plastic polymers. This study, for the first time, used ACP as a novel method for MPs treatment. Polypropylene (PP) and low-density polyethylene (LDPE) were used to prepare model MPs. The effects of plasma working gas (oxygen, nitrogen, or their mixture) and post-ACP treatment storage (24 h) on MPs were studied. ACP treatments for 30 min successfully degraded both MPs, by 1.4-11.3% in weight. PP MPs had larger weight reduction than LDPE and the ACP of mixture gas was most effective. PP MPs also showed increased carbonyl index after treatments, to up to 6.89, indicating hydrolytic degradation. For LDPE MPs, oxygen ACP caused more oxidation, but storage did not have an enhancing effect. The results of physicochemical analyses indicated that MPs degradation by ACP was possibly mainly through oxidative and hydrolytic reactions, but further characterizations are needed. This study proves that ACP is a promising strategy to remediate MPs pollution, and thus has great potential for addressing the severe challenges of MPs that the food and agriculture sectors are currently facing.
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Microplásticos , Gases em Plasma , Contaminantes Químicos del Agua , Gases em Plasma/química , Contaminantes Químicos del Agua/análisis , Restauración y Remediación Ambiental/métodos , Polietileno/química , PolipropilenosRESUMEN
Formononetin (FMNT) is a secondary metabolite of flavonoids abundant in legumes and graminaceous plants such as Astragalus mongholicus Bunge [Fabaceae; Astragali radix] and Avena sativa L. [Poaceae]. Astragalus is traditionally used in Asia countries such as China, Korea and Mongolia to treat inflammatory diseases, immune disorders and cancers. In recent years, inflammation and oxidative stress have been found to be associated with many diseases. A large number of pharmacological studies have shown that FMNT, an important bioactive metabolite of Astragalus, has a profoundly anti-inflammatory and antioxidant potential. This review focuses on providing comprehensive and up-to-date findings on the efficacy of the molecular targets and mechanisms involve of FMNT and its derivatives against inflammation and oxidative stress in both in vitro and in vivo. Relevant literature on FMNT against inflammation and oxidative stress between 2013 and 2023 were analyzed. FMNT has antioxidant and anti-inflammatory potential and shows mild or no toxicity in various diseases. Moreover, in the medical field, FMNT has shown potential in the prevention and treatment of cancers, neurological diseases, fibrotic diseases, allergic diseases, metabolic diseases, cardiovascular diseases, gastrointestinal diseases and autoimmune diseases. Thus, it is expected to be utilized in more products in the medical, food and cosmetic industries in the future.
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Microbubbles (MBs) were incorporated into calcium chloride solution as a novel freezing medium for immersion freezing of grape tomato. The effects of MB size (39, 43, 48 µm mean diameter), entrapped gas (air, N2, CO2) and freezing temperature (-10, -15, -20 °C) on the freezing behavior and quality attributes of tomato were investigated. MBs increased the nucleation temperature from -7.4 to -3.5 °C and reduced the onset time of nucleation from 5.8 to 2.9 min at freezing temperature of -20 °C, which facilitated the formation of small ice crystals within tomato. MB-assisted freezing reduced the drip loss by 13.7-17.0% and improved the firmness of tomato, particularly when MB size and freezing temperature decreased. Freezing tomato with air-MBs did not compromise its nutritional quality, using N2- and CO2-MBs even increased its lycopene content, by 31% and 23%, respectively. The results proved the preservation effect of MBs on fruit during immersion freezing. This study can benefit the fruit and vegetable industry by providing an efficient freezing technology for producing frozen products with high sensory and nutritional quality.
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Conservación de Alimentos , Congelación , Frutas , Microburbujas , Solanum lycopersicum , Solanum lycopersicum/química , Frutas/química , Conservación de Alimentos/métodos , Conservación de Alimentos/instrumentación , Manipulación de Alimentos/instrumentación , Licopeno/química , Valor NutritivoRESUMEN
This study aims to explore the potential mechanism of action in the intervention of acute lung injury(ALI) based on the blood entry components of Ganke Granules in rats and in conjunction with network pharmacology, molecular docking, and animal experimental validation. The blood entry components of Ganke Granules in rats were imported into the SwissTargetPrediction platform to predict drug targets, and ALI-related targets were collected from the disease database. Intersections were taken, and protein-protein interaction(PPI) networks were constructed to screen the core targets, followed by Gene Ontology(GO) functional and Kyoto encyclopedia of genes and gnomes(KEGG) pathway enrichment analyses. A "blood entry components-target-pathway-disease" network was constructed, and the core components for disease intervention based on their topological parameters were screened. Molecular docking was used to predict the binding ability of the core components to key targets. The key targets of Ganke Granules in the intervention of ALI were verified by the lipopolysaccharide(LPS)-induced ALI mouse model. Through PPI topological parameter analysis, the top six key targets of STAT3, SRC, HSP90AA1, MAPK3, HRAS, and MAPK1 related to ALI were obtained. GO functional analysis showed that it was mainly related to ERK1 and ERK2 cascade, inflammatory response, and response to LPS. KEGG analysis showed that the main enrichment pathways were MAPK, neutrophil extracellular trap(NET) formation, and so on. Six core components(schizantherin B, schisandrin, besigomsin, harpagoside, isotectorigenin, and trachelanthamine) were filtered out by the "blood entry components-target-pathway-disease" network based on the analysis of topological parameters. Molecular docking results showed that the six core components and Tectoridin with the highest content in the granules had a high affinity with the key targets of MAPK3, SRC, MAPK1, and STAT3. In vivo experiment results showed that compared with the model group, Ganke Granules could effectively alleviate LPS-induced histopathological injury in the lungs of mice and reduce the percentage of inflammatory infiltration. The total protein content, nitric oxide(NO) level, myeloperoxidase(MPO) content, tumor necrosis factor-α(TNF-α), gamma interferon(IFN-γ), interleukin-1ß(IL-1ß), interleukin-6(IL-6), vascular endothelial growth factor(VEGF), and chemokine(C-X-C motif) ligand 1(CXCL1) chemokines in bronchoalveolar lavage fluid(BALF) were decreased, and the expression levels of lymphocyte antigen 6G(Ly6G), citrullinated histones 3(Cit-H3), and phosphorylated proteins SRC, ERK1/2, and STAT3 in lung tissue were significantly down-regulated. In conclusion, Ganke Granules could effectively inhibit the inflammatory response of ALI induced by LPS, protect lung tissue, regulate the release of inflammatory factors, and inhibit neutrophil infiltration and NET formation, and the mechanism of action may be related to inhibiting the activation of SRC/ERK1/2/STAT3 signaling pathway.
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Lesión Pulmonar Aguda , Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Farmacología en Red , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Ratones , Ratas , Masculino , Mapas de Interacción de Proteínas , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Ratas Sprague-Dawley , HumanosRESUMEN
Background: Pathophysiology plays a significant role in the scientific study of ischemic stroke, and has attracted increasing interest from researchers in the field. However, a comprehensive bibliometric analysis is lacking in this field. The purpose of this study is to identify the current research status and hotspots of ischemic stroke pathophysiology from a bibliometric perspective. Methods: The Web of Science Core Collection database was searched for articles published from 1990 to 2022. CiteSpace, VOSviewer, and R package "bibliometrix" software were used to analyze countries/regions, institutions, journals, authors, papers, and keywords to predict the latest trends in ischemic stroke pathophysiology research. Results: This analysis collected 7578 records of ischemic stroke pathophysiology. China and America emerged as the leading countries in this field, with Harvard University being the most active institution. Among journals and authors in this field, journal Stroke and author Gregory YH Lip published the most papers, while Nature Medicine was the journal with the highest citation per article. Keywords and co-citation clusters were closely related to "central nervous system", "mechanisms", "biochemistry & molecular biology" and "radiology, nuclear medicine & medical imaging", while other related fields, such as peripheral organs damage induced by the central nervous system and rehabilitation after ischemic stroke, require further research efforts. Conclusion: This is the first bibliometric study that comprehensively mapped out the knowledge structure and development trends of ischemic stroke pathophysiology in recent 32 years, which may provide a reference for scholars to explore ischemic stroke pathophysiology.
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PURPOSE: The Centiloid project helps calibrate the quantitative amyloid-ß (Aß) load into a unified Centiloid (CL) scale that allows data comparison across multi-site. How the smaller regional amyloid converted into CL has not been attempted. We first aimed to express regional Aß deposition in CL using [18F]Flutemetamol and evaluate regional Aß deposition in CL with that in standardized uptake value ratio (SUVr). Second, we aimed to determine the presence or absence of focal Aß deposition by measuring regional CL in equivocal cases showing negative global CL. METHODS: Following the Centiloid project pipeline, Level-1 replication, Level-2 calibration, and quality control were completed to generate corresponding Centiloid conversion equations to convert SUVr into Centiloid at regional levels. In equivocal cases, the regional CL was compared with visual inspection to evaluate regional Aß positivity. RESULTS: 14 out of 16 regional conversions from [18F]Flutemetamol SUVr to Centiloid successfully passed the quality control, showing good reliability and relative variance, especially precuneus/posterior cingulate and prefrontal regions with good stability for Centiloid scaling. The absence of focal Aß deposition could be detected by measuring regional CL, showing a high agreement rate with visual inspection. The regional Aß positivity in the bilateral anterior cingulate cortex was most prevalent in equivocal cases. CONCLUSION: The expression of regional brain Aß deposition in CL with [18F]Flutemetamol has been attempted in this study. Equivocal cases had focal Aß deposition that can be detected by measuring regional CL.
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Péptidos beta-Amiloides , Compuestos de Anilina , Benzotiazoles , Tomografía de Emisión de Positrones , Radiofármacos , Humanos , Péptidos beta-Amiloides/metabolismo , Femenino , Masculino , Anciano , Tomografía de Emisión de Positrones/métodos , Reproducibilidad de los Resultados , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/diagnóstico por imagen , Persona de Mediana Edad , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , CalibraciónRESUMEN
The development of oral film with diverse colors and customized nutrition is in line with the innovation of emerging food. In this study, polychromatic system was formed by regulating the ratio of phycocyanin (PC) to blueberry anthocyanin (BA). Further, chondroitin sulfate (CS) was utilized to achieve color-enhanced and homeostatic effects on PC-BA, and κ-carrageenan (KC) - starch complex was exploited as printing ink to construct oral film system. The color-enhanced effect of CS is mainly related to the complexation of sulfate groups, and the film-forming substrates are combined mainly through hydrogen bonding. In addition, the proportion of KC modulated the gel structure of printing ink, and affected 3D printability and physical properties of oral film. OF II (1.5 % KC content) had a uniform and dense network structure, with the most stable color and the highest BA retention (70.33 %) after 8 d of light exposure. Importantly, OF II had an excellent slow-release effect, and BA release rate was as high as 92.52 %. The optimized components can form polychromatic oral film with controllable color and structure, and provide new insights for the creation of sensory personalized and nutritionally customized food.
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Antocianinas , Sulfatos de Condroitina , Carragenina , Ficocianina , Almidón , Excipientes , Homeostasis , Impresión TridimensionalRESUMEN
Aim and background: This study attempted to identify similarities and differences in adverse events (AEs) between human epidermal growth factor receptor 2 (HER2) inhibitors, especially those related to hemorrhagic events and nervous system disorders. Methods: This study summarized the types, frequencies, and system organ classes (SOCs) of AEs of HER2 inhibitors. The US Food and Drug Administration Adverse Event Reporting System (FAERS) data from January 2004 through March 2022 was collected and analyzed. Disproportionality analyses were conducted to detect AEs signals for every HER2 inhibitor. The chi-square test, Wilcoxon test, and descriptive analysis were used to compare the differences of AEs for specific SOCs or drugs. Results: A total of 47,899 AE reports were obtained for eight HER2 inhibitors. Trastuzumab-related AEs were reported in the highest number and combination of regimens. In monotherapy, trastuzumab had the highest reported rate of cardiac disorders-related AEs (24.0%). However, small-molecule drugs exceeded other drugs in the reported rates of AEs related to gastrointestinal disorders, metabolism and nutrition disorders. The highest reported rates of respiratory disorders (47.3%) and hematologic disorders (22.4%) were associated with treatment with trastuzumab deruxtecan (T-DXd). Patients treated with trastuzumab emtansine (TDM-1) had the highest reported rate (7.28%) of hemorrhagic events, especially intracranial haemorrhage events. In addition, patients treated with TDM-1 with concomitant thrombocytopenia were likely to experience hemorrhagic events compared to other HER2 inhibitors (p < 0.001). The median time to onset of intracranial haemorrhage associated with trastuzumab (0.5 months) and TDM-1 (0.75 months) was short. However, there was no significant difference in median time to onset intracranial haemorrhage between patients in different age groups or with different outcomes. Disproportionality analysis results reveal that cerebral haemorrhage is a positive signal associated with T-DXd and TDM-1. In addition, tucatinib was the drug with the highest rate of reported nervous system disorders (31.38%). Memory impairment (83 cases) is a positive signal for tucatinib. Conclusion: The types and reporting rates of AEs associated with different HER2 inhibitors vary across multiple systems. In addition, hemorrhagic events concomitant with TDM-1 treatment and nervous system disorders concomitant with tucatinib treatment may be worthy of attention.
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Oral film is a novel functional carrier, which can provide a new pathway for the efficient absorption of anthocyanin. However, anthocyanin homeostasis in oral film is a prerequisite for achieving efficient absorption and utilization of anthocyanin. Herein, three sulfated polysaccharides, including chondroitin sulfate (CS), fucoidin (FU) and λ-carrageenan (λ-CG), were complexed with blueberry anthocyanin (BA) to prepare oral film formulations using hydroxypropyl methylcellulose (HPMC) as a film-forming matrix. The addition of three sulfated polysaccharides improved the stability of BA in content and color, which were associated with interactions between BA and polysaccharides. The BA retention rate of CS-BA/HPMC system increased 5.5-fold after 8 d of light-accelerated storage compared with the control group, showing the best homeostasis effect. CS and λ-CG enhanced the elongation at break and prolonged disintegration time of oral films. The addition of FU made the oral film denser and smoother, and had the highest BA release (75.72 %) in the simulated oral cavity system. In addition, the oral films of three sulfated polysaccharides complexed with BA showed superior antioxidant capacity. The present study provides new insights into the application of anthocyanin in film formulation carriers.
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Antocianinas , Sulfatos , Preparaciones de Acción Retardada , Polisacáridos , Carragenina , Sulfatos de Condroitina , Derivados de la Hipromelosa/química , HomeostasisRESUMEN
OBJECTIVES: Although observational studies have suggested a link between hypothyroidism and myasthenia gravis (MG), a causal relationship has not been established. We aimed to investigate the causal association using a two-sample Mendelian randomization (MR) study. METHODS: Using summary statistics from genome-wide association studies involving 494,577 and 38,243 individuals, single-nucleotide polymorphisms exhibiting no linkage disequilibrium (r2 ≤ 0.001) and displaying significant differences (p ≤ 5 × 10-8) were selected for hypothyroidism and MG. To assess the potential causality relationship between hypothyroidism and MG, MR analysis was conducted using inverse variance weighted (IVW), weighted median method, and MR-Egger. The MR-Egger regression, heterogeneity test, pleiotropy test, and leave-one-out sensitivity test were employed to examine sensitivity analyses. In addition, validation datasets were used to validate the relevant results. RESULTS: Genetic liability to hypothyroidism was positively associated with MG (IVW, OR: 1.36, 95% CI: 1.17-1.58, p = 7.53 × 10-05; weighted median, OR: 1.19, 95% CI: 0.70-2.02, p = 0.522; MR-Egger, OR: 1.19, 95% CI: 0.98-1.45, p = 0.080). Among the three MR methods, the correlation between hypothyroidism and MG genetic prediction was consistent. The independent validation set (IVW, OR: 466.47, 95% CI: 4.70 -46,285.95, p = 0.01) further supported this. Additionally, bidirectional studies showed that using IVW, there was no reverse causality (OR: 1.104, 95%CI: 0.96-1.27, p = 0.170). DISCUSSION: This MR study showed that hypothyroidism can increase the risk of MG. Further investigation into the underlying mechanisms of this potential causality is warranted to offer novel therapeutic options for MG in the future.
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Hipotiroidismo , Miastenia Gravis , Humanos , Estudio de Asociación del Genoma Completo , Hipotiroidismo/complicaciones , Hipotiroidismo/genética , Desequilibrio de Ligamiento , Análisis de la Aleatorización Mendeliana , Miastenia Gravis/complicaciones , Miastenia Gravis/genéticaRESUMEN
OBJECTIVES: To assess the occurrence of cardiotoxicity in patients with tumors receiving anthracycline-based chemotherapy, especially for sarcomas. METHODS: This study summarized the types and frequency of adverse events (AEs) for three anthracyclines from the FDA adverse event reporting system (FAERS) database. FAERS data from January 2004 to June 2022 were collected and analyzed. Disproportionality analyses, logistic regression, and descriptive analysis were used to compare the differences in cardiac disorders. A retrospective cohort study was conducted in a single center between December 2008 and May 2022. Our hospital-treated patients with bone and soft tissue sarcomas (BSTSs) with anthracycline-containing chemotherapy were analyzed. Serum markers, echocardiography, and electrocardiography have been used to evaluate cardiotoxic events. RESULTS: One hundred thousand and seventy-five AE reports were obtained for doxorubicin (ADM), epirubicin (EPI), and liposome doxorubicin (L-ADM) from the FAERS database. ADM (OR = 3.1, p < 0.001), EPI (OR = 1.5, p < 0.001), and sarcomas (OR = 1.8, p < 0.001) may increase the probability of cardiac disorders. Cardiac failure, cardiotoxicity, and cardiomyopathy were anthracyclines' top 3 frequent AEs. Among patients receiving ADM-containing therapy, those with ADM applied at doses ≥75 mg/m2 /cycle were more likely to develop cardiac disorders than the other subgroups (OR = 3.5, p < 0.001). Patients younger than 18 are more likely to benefit from dexrazoxane prevention of cardiac failure. Six hundred and eighty-three patients with BSTSs receiving anthracycline-based chemotherapy were analyzed in our center. Patients receiving ADM-containing chemotherapy were likelier to experience abnormalities in serum troponin-T and left ventricular ejection fraction (p < 0.05). 2.0% (6/300) of patients receiving ADM-containing chemotherapy required adjustment of the chemotherapy regimen because of cardiotoxicity, whereas none were in the EPI or L-ADM groups. CONCLUSIONS AND RELEVANCE: Among patients receiving anthracycline-containing therapy, patients with BSTSs were more likely to develop cardiac disorders than other tumors. In addition, patients with BSTSs receiving ADM chemotherapy had a higher likelihood of cardiotoxic events than those receiving EPI or L-ADM.
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Cardiopatías , Insuficiencia Cardíaca , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Antraciclinas/uso terapéutico , Cardiotoxicidad/etiología , Estudios Retrospectivos , Volumen Sistólico , Función Ventricular Izquierda , Antibióticos Antineoplásicos/efectos adversos , Cardiopatías/inducido químicamente , Cardiopatías/diagnóstico , Cardiopatías/epidemiología , Doxorrubicina/uso terapéutico , Epirrubicina , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológicoRESUMEN
BACKGROUND: Pancreatic cancer is difficult to be diagnosed early clinically, while often leads to poor prognosis. If optimal personalized treatment plan can be provided to pancreatic cancer patient at an earlier stage, this can greatly improve overall survival (OS). Circulating tumor cells (CTCs) are a collective term for various types of tumor cells present in the peripheral blood (PB), which are formed by detachment during the development of solid tumor lesions. Most CTCs undergo apoptosis or are phagocytosed after entering the PB, whereas a few can escape and anchor at distal sites to develop metastasis, increasing the risk of death for patients with malignant tumors. AIM: To investigate the significance of CTCs in predicting the prognosis of early pancreatic cancer patients. METHODS: The PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine, and ChinaInfo databases were searched for articles published through December 2022. Studies were considered qualified if they included patients with early pancreatic cancer, analyzed the prognostic value of CTCs, and were full papers reported in English or Chinese. Researches were selected and assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and the Newcastle-Ottawa Scale criteria. We used a funnel plot to assess publication bias. RESULTS: From 1595 publications, we identified eight eligible studies that collectively enrolled 355 patients with pancreatic cancer. Among these original studies, two were carried out in China; three in the United States; and one each in Italy, Spain, and Norway. All eight studies analyzed the relevance between CTCs and the prognosis of patients with early-stage pancreatic cancer after surgery. A meta-analysis showed that the patients that were positive pre-treatment or post-treatment for CTCs were associated with decreased OS [hazard ratio (HR) = 1.93, 95% confidence interval (CI): 1.197-3.126, P = 0.007] and decreased relapse-free/disease-free/progression-free survival (HR = 1.27, 95%CI: 1.137-1.419, P < 0.001) in early-stage pancreatic cancer. Additionally, the results suggest no statistically noticeable publication bias for overall, disease-free, progression-free, and recurrence-free survival. CONCLUSION: This pooled meta-analysis shows that CTCs, as biomarkers, can afford reliable prognostic information for patients with early-stage pancreatic cancer and help develop individualized treatment plans.
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Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, and its pathological mechanisms are thought to be closely linked to apoptosis. Anoikis, a specific type of apoptosis, has recently been suggested to play a role in the progression of Parkinson's disease; however, the underlying mechanisms are not well understood. To explore the potential mechanisms involved in PD, we selected genes from the GSE28894 dataset and compared their expression in PD patients and healthy controls to identify differentially expressed genes (DEGs), and selected anoikis-related genes (ANRGs) from the DEGs. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression approach and multivariate logistic regression highlighted five key genes-GSK3B, PCNA, CDC42, DAPK2, and SRC-as biomarker candidates. Subsequently, we developed a nomogram model incorporating these 5 genes along with age and sex to predict and diagnose PD. To evaluate the model's coherence, clinical applicability, and distinguishability, we utilized receiver operating characteristic (ROC) curves, the C-index, and calibration curves and validated it in both the GSE20295 dataset and our center's external clinical data. In addition, we confirmed the differential expression of the 5 model genes in human blood samples through qRT-PCR and Western blotting. Our constructed anoikis-related PD diagnostic model exhibits satisfactory predictive accuracy and offers novel insights into both diagnosis and treatment strategies for Parkinson's disease while facilitating its implementation in clinical practice.
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The full combination of high sensitivity indication and long-lasting bacteriostatic function is an innovative need to meet the practicality of intelligent film packaging systems for food products. Hence, Blueberry anthocyanins (BA) copigmentated by ferulic acid (FA) was used as an indicator, and cinnamon essential oil (CO) encapsulated by ß-cyclodextrin (ß-CD) as a bacteriostat, potato starch (PS) as a film-forming substrate to prepared a dual-function starch-based intelligent active packaging film with pH indicator and antibacterial function. FA had the best copigmentation effect with a threefold increase in a value compared to other phenolic acids. The ΔE value increased from 3.24 to 5.13 at pH 2-8, and the change was still prominent in acid-base alternating test, indicating a high response sensitivity. Notably, the yellow gamut of indicating terminus increased its visibility to the naked eye. The release behavior of CO from film was in line with Fick's diffusion. Meanwhile, the release of CO delayed to about 90 h through ß-cyclodextrin encapsulation, showing a high growth-inhibition rate in E. coli and S. aureus of almost 100 %. In this study, a dual-function film with indication and bacteriostasis was prepared and enhanced with both, expanding its wide application in intelligent packaging of fresh food.
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Aceites Volátiles , beta-Ciclodextrinas , Tiram/farmacología , Almidón/farmacología , Antocianinas/farmacología , Escherichia coli , Staphylococcus aureus , Aceites Volátiles/farmacología , beta-Ciclodextrinas/farmacología , Conservación de Alimentos , Embalaje de Alimentos , Concentración de Iones de HidrógenoRESUMEN
Polyphenols have received considerable attention for their promotive effects on colonic health. However, polyphenols are mostly sensitive to harsh gastrointestinal environments, thus, must be protected. It is necessary to design and develop a colon-targeted delivery system to improve the stability, colon-targeting and bioavailability of polyphenols. This paper mainly introduces research on colon-targeted controlled release of polyphenols. The physiological features affecting the dissolution, release and absorption of polyphenol-loaded delivery systems in the colon are first discussed. Simultaneously, the types of colon-targeted carriers with different release mechanisms are described, and colon-targeting assessment models that have been studied so far and their advantages and limitations are summarized. Based on the current research on polyphenols colon-targeting, outlook and reflections are proposed, with the goal of inspiring strategic development of new colon-targeted therapeutics to ensure that the polyphenols reach the colon with complete bioactivity.
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BACKGROUND: Dementia presents a significant burden to patients and healthcare systems worldwide. Early and accurate diagnosis, as well as differential diagnosis of various types of dementia, are crucial for timely intervention and management. However, there is currently a lack of clinical tools for accurately distinguishing between these types. OBJECTIVE: This study aimed to investigate the differences in the structural white matter (WM) network among different types of cognitive impairment/dementia using diffusion tensor imaging, and to explore the clinical relevance of the structural network. METHODS: A total of 21 normal control, 13 subjective cognitive decline (SCD), 40 mild cognitive impairment (MCI), 22 Alzheimer's disease (AD), 13 mixed dementia (MixD), and 17 vascular dementia (VaD) participants were recruited. Graph theory was utilized to construct the brain network. RESULTS: Our findings revealed a monotonic trend of disruption in the brain WM network (VaDâ>âMixDâ>âADâ>âMCIâ>âSCD) in terms of decreased global efficiency, local efficiency, and average clustering coefficient, as well as increased characteristic path length. These network measurements were significantly associated with the clinical cognition index in each disease group separately. CONCLUSION: These findings suggest that structural WM network measurements can be utilized to differentiate between different types of cognitive impairment/dementia, and these measurements can provide valuable cognition-related information.