A diagnostic model for Parkinson's disease based on circadian rhythm-related genes.

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, RT‒qPCR 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.

Expression of regional brain amyloid-ß deposition with [18F]Flutemetamol in Centiloid scale -a multi-site study.

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.

[Mechanism of Ganke Granules intervening acute lung injury based on network pharmacology and experimental verification].

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.

Hypoglycemic bioactivity of anthocyanins: A review on proposed targets and potential signaling pathways.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with complicated interrelationships responsible for initiating its pathogenesis. Novel strategies for the treatment of this devastating disease have attracted increasing attention worldwide. Anthocyanins are bioactive compounds that are widely distributed in the plant kingdom, and multiple studies have elucidated their beneficial role in preventing and managing T2DM. This review summarizes and comments on the hypoglycemic actions of anthocyanins from the perspective of molecular mechanisms and different target-related signaling pathways in vitro, in vivo, and clinical trials. Anthocyanins can ameliorate T2DM by functioning as carbohydrate digestive enzyme inhibitors, facilitating glucose transporter 4 (GLUT4) translocation, suppressing the effectiveness of dipeptidyl peptidase IV (DPP-IV), promoting glucagon-like peptide-1 (GLP-1) secretion, inhibiting protein tyrosine phosphatase 1B (PTP1B) overexpression, and interacting with sodium-glucose co-transporter (SGLT) to delay glucose absorption in various organs and tissues. In summary, anthocyanin is a promising and practical small molecule that can hyperglycemic symptoms and accompanying complications suffered by patients with diabetes. However, rational and potent doses for daily intake and clinical studies are required in the future.

Lonicera caerulea (Haskap berries): a review of development traceability, functional value, product development status, future opportunities, and challenges.

Lonicera caerulea is a honeysuckle plant with a long development history. It is defined as a "homology of medicine and food" fruit because it is rich in bioactive substances. By-products (such as pomace, leaves, stems, and flowers), which also have beneficial values, will be produced during processing. Nevertheless, the reuse of derivatives and the further development of new products of Lonicera caerulea are still a challenge. Firstly, this paper traced the development history of Lonicera caerulea and summarized its primary nutrients and bioactive substances, subsequently discussed the research progress and underlying molecular mechanisms of its functional properties, and introduced the application and potential of Lonicera caerulea in the fields of food, health products, cosmetics, medicine, and materials. Finally, this paper put forward the future research direction to promote the development of the Lonicera caerulea industry. To sum up, Lonicera caerulea, as a potential raw material, can be used to produce more functional products. Besides, more in-depth clinical trials are needed to clarify the specific molecular mechanism of the practical components of Lonicera caerulea and improve the rate of development and utilization.HighlightsThe original species of Lonicera caerulea subgroup had appeared on the earth as early as the end of the third century.Lonicera caerulea has been introduced into North America since the 18th century, but the introduction process has not ended until now.Lonicera caerulea widely exists in Eurasia and North America and it has excellent cold tolerance, early maturity and ornamental.The fruits, stems, leaves and flowers of Lonicera caerulea all have bioactive value, but the specific molecular mechanism and utilization need to be improved.Lonicera caerulea has been widely used in food, medicine, health products, cosmetics and materials, but there are still great challenges.

Colon-targeted delivery of polyphenols: construction principles, targeting mechanisms and evaluation methods.

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.

Identifying the potential role of serum miR-20a as a biomarker for olfactory dysfunction in patients with Parkinson's disease.

INTRODUCTION: Olfactory dysfunction (OD), one of the most common non-motor symptoms in Parkinson's disease (PD), is a cardinal prodromal symptom that can appear years before the onset of motor symptoms. Ongoing studies have demonstrated that microRNAs (miRNAs) are suitable biomarkers for PD, while there is a lack of robust miRNAs that can serve as markers for OD in PD. METHODS: The concordantly differentially expressed miRNAs (DE miRNAs) in the damaged olfactory system were first identified in 2 OD-related Gene Expression Omnibus (GEO) datasets. Then, they were verified in another PD-related GEO dataset and only one miRNA (miR-20a) was found to be significantly altered. Serum levels of miR-20a were further measured by qPCR in 79 PD patients with OD (PD-OD), 52 PD patients without OD (PD-NOD), and 52 healthy controls (HC). Objective measure of OD was defined by 16-item Sniffin' Sticks odor identification test. All the participants underwent a demographic and comprehensive PD-related clinical assessment. RESULTS: Our results proved that miR-20a was significantly downregulated in PD-OD compared with PD-NOD and the area under curve (AUC) for OD detection by miR-20a was 0.803 (95% confidence interval, 0.724-0.883). In addition, PD-OD had higher scores of Movement Disorder Society-Unified Parkinson's Disease Rating Scale (UPDRS) II, Hoehn and Yahr stage (H-Y), Non-Motor Symptoms Scale (NMSS) 3, NMSS 5, NMSS 9, Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Scale (HAMA), Activity of Daily Living (ADL), and lower scores of Mini-Mental State Examination (MMSE) and 39-item PD Quality of Life Questionnaire (PDQ-39) than PD-NOD. Binary regression model further presented that lower expressions of miR-20a and poorer cognitive function acted as promoting factors in the development of OD. CONCLUSION: Our results suggest that miR-20a could be a novel biomarker for OD in PD and PD-OD patients tend to have higher disease stage, poorer motor aspects of experiences of daily living, worse cognitive scores, and inferior quality of life, and were more likely to have mental disorders. Cognitive function, in particular, is strongly associated with OD in PD patients.

OI inhibits development of ovarian cancer by blocking crosstalk between cancer cells and macrophages via HIF-1α pathway.

Intraperitoneal implantation of ovarian cancer (OC) decreases the survival rate in clinical practice. However, there are still great deficiencies in the therapeutic strategies of inhibiting the metastasis of OC. Here, we showed that 4-octyl itaconate (OI, a cell-permeable itaconate derivative) treatment didn't influence the development of OC in vitro. Instead, OI treatment repressed the activation of peritoneal macrophages and downregulated the expression of proinflammatory factors in mice bearing OC. Besides, OI inhibited the angiogenesis of OC tissues by downregulating HIF-1α of OC that was induced by proinflammatory factors from activated macrophages. In conclusion, our findings demonstrate that OI suppresses metastasis of ovarian cancer by blocking crosstalk between cancer cells and macrophages via HIF-1α pathway, providing a potential therapeutic strategy for metastasis of OC.

3D food printing: Applications of plant-based materials in extrusion-based food printing.

As an emerging digital production technology, 3D food printing intends to meet the demand for customized food design, personalized nutrition, simplification of the food supply chain system, and greater food material diversity. Most 3D food printing studies focus on the development of materials for extrusion-based food printing. Plant-based foods are essential for a healthy diet, and they are growing in popularity as their positive effects on human health gain wider recognition. The number of original studies on plant-based printable materials has increased significantly in the past few years. Currently, there is an absence of a comprehensive systematic review on the applications of plant-based materials in extrusion-based food printing. Thus, this review aims to provide a more intuitive overview and guidance for future research on 3D printing of plant-based materials. The requirements, classifications, and binding mechanisms of extrusion-based food printing materials are first summarized. Additionally, notable recent achievements and emerging trends involving the use of plant-based materials in extrusion-based food printing are reviewed across three categories, namely, hot-melt (e.g., chocolate), hydrogel, and soft (e.g., cereal- and fruit/vegetable-based) materials. Finally, the challenges facing 3D food printing technology as well as its future prospects are discussed.

Association between Cognitive Decline and Altered Cerebral Perfusion in Adults with Moyamoya Disease after Revascularization.

INTRODUCTION: Certain studies have observed that patients with moyamoya disease (MMD) have cognitive decline after revascularization. Thus, this study analyzed the relationship between cognitive decline and altered cerebral perfusion after revascularization. METHODS: Here, 313 adult patients with MMD underwent single unilateral revascularization. First, cognitive function was scored using a Mini-Mental Scale (MMSE) and Montreal cognitive function scale (MoCA) before and 3 months after the operation (superficial temporal artery-middle cerebral artery anastomosis with encephalo-myo-synangiosis). Then, computed tomography perfusion was performed before and 1 week after the operation to assess the cerebral perfusion. RESULTS: Our data showed that cognitive function decreased in 55 cases (17.6%) after revascularization. Furthermore, the incidence of cerebral hyperperfusion (CHP) was significantly higher in the cognitive decline group (49/55) than in the cognitive nondecline group (89.1% vs. 5.4%, p < 0.001). Results also showed that although all 55 patients had postoperative cognitive decline, 47 experienced relative cerebral blood flow (CBF) decrease at a relatively distant area of the anastomosis compared with that before the operation, which was significantly higher than in patients without cognitive decline (85.5% vs. 1.94%, p < 0.001). In addition, 41 patients had a simultaneous occurrence of local CHP and paradoxical CBF decrease at a relatively distant anastomosis area, which indicated the incident of watershed shift (WS). As observed, WS occurred in 74.5% of patients with cognitive decline, significantly higher than in patients without cognitive decline (74.5% vs. 0%, p < 0.0001). Through multiple logistic regression analysis, WS was also observed to be a strong independent risk factor for predicting postoperative cognitive decline 3 months after revascularization (odds ratio 17.780, 95% confidence interval 1.668-18.564; p = 0.017). CONCLUSION: Therefore, cognitive decline in patients with MMD after revascularization is related to WS, leading to an uneven distribution of CBF.

Benefits of Iron Chelators in the Treatment of Parkinson's Disease.

As a novel discovered regulated cell death pattern, ferroptosis has been associated with the development of Parkinson's disease (PD) and has attracted widespread attention. Nevertheless, the relationship between ferroptosis and PD pathogenesis is still unclear. This study aims to investigate the effect of iron overload on dopaminergic (DA) neurons and its correlation with ferroptosis. Here we use nerve growth factor (NGF) induced PC12 cells which are derived from pheochromocytoma of the rat adrenal to establish a classical PD in vitro model. We found significantly decreased cell viability in NGF-PC12 cell under ammonium ferric citrate (FAC) administration. Moreover, excessive intracellular iron ions induced the increase of (reactive oxygen species) ROS release as well as the decrease of mitochondrial membrane potential in PC12-NGF cells. In addition, we also found that overloaded iron can activate cell apoptosis and ferroptosis pathways, which led to cell death. Furthermore, MPP-induced PD cells were characterized by mitochondrial shrinkage, decreased expression of glutathione peroxidase 4 (Gpx4) and ferritin heavy chain (FTH1), and increased divalent metal transporter (DMT1) and transferrin receptor 1 (TfR1) expression level. In contrast, Lip-1 and DFO increased the expression level of GPX4 and FTH1 compared to MPP-induced PD cell. In conclusion, we indicated that overloaded intracellular iron contributes to neurons death via apoptosis and ferroptosis pathways, while DFO, an iron chelator, can inhibit ferroptosis in order to protect the neurons in vitro.

Fabrication and characterization of gum arabic- and maltodextrin-based microcapsules containing polyunsaturated oils.

BACKGROUND: Polyunsaturated oils have various health-promoting effects, however, they are highly prone to oxidation. Encapsulation using biopolymers is one of the most effective strategies to enhance oil stability. This research examined the potential of gum arabic and maltodextrin for microencapsulation of omega-3 rich oils, aiming to enhance encapsulation efficiency and stability of encapsulated oil. RESULTS: We encapsulated fish and flaxseed oils by emulsification-spray drying. Spray-dried microcapsules were prepared by oil-in-water emulsions consisting of 10 wt% oil and 30 wt% biopolymer (gum arabic, maltodextrin, or their mixture). Results showed that both microcapsules were spherical in shape with surface shrinkage, and exhibited amorphous structures. Gum arabic-based microcapsules had higher encapsulation efficiency as well as better storage stability for both types of oil. Flaxseed oil microcapsules generally had higher oxidative stability regardless of the type of wall material. CONCLUSIONS: Through a comprehensive characterization of the physical and chemical properties of the emulsions and resulting microcapsules, we proved gum arabic to be a more effective wall material for polyunsaturated oil microencapsulation, especially flaxseed oil. This study provides a promising approach to stabilize oils which are susceptible to deterioration, and facilitates their wider uses as food and nutraceutical products. © 2021 Society of Chemical Industry.

A systematic review of atypical Alzheimer's disease including behavioural and psychological symptoms.

Alzheimer's disease (AD) is the commonest cause of dementia, characterized by the clinical presentation of progressive anterograde episodic memory impairment. However, atypical presentation of patients is increasingly recognized. These atypical AD include logopenic aphasia, behavioural variant AD, posterior cortical atrophy, and corticobasal syndrome. These atypical AD are more common in patients with young onset AD before the age of 65 years old. Since medical needs (including the behavioural and psychological symptoms of dementia) of atypical AD patients could be different from typical AD patients, it is important for clinicians to be aware of these atypical forms of AD. In addition, disease modifying treatment may be available in the future. This review aims at providing an update on various important subtypes of atypical AD including behavioural and psychological symptoms.

Effect of microbubbles on immersion freezing of grape tomato.

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.

Atmospheric cold plasma as a novel approach to remediating microplastics pollution in water.

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.

Bidirectional association between hypothyroidism and myasthenia gravis: a Mendelian randomized study.

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.

Anthocyanin-loaded milk-derived extracellular vesicles nano-delivery system: Stability, mucus layer penetration, and pro-oxidant effect on HepG2 cells.

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.

Potential mechanisms of formononetin against inflammation and oxidative stress: a review.

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.

Comparing the difference of adverse events with HER2 inhibitors: a study of the FDA adverse event reporting system (FAERS).

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.