Exosome detection via the ultrafast-isolation system: EXODUS.

Exosomes have shown great potential in disease diagnostics and therapeutics. However, current isolation approaches are burdensome and suffer from low speed, yield and purity, limiting basic research and clinical applications. Here, we describe an efficient exosome detection method via the ultrafast-isolation system (EXODUS) that allows automated label-free purification of exosomes from varied biofluids. We obtained the ultra-efficient purification of exosomes by negative pressure oscillation and double coupled harmonic oscillator-enabled membrane vibration. Our two coupled oscillators generate dual-frequency transverse waves on the membranes, enabling EXODUS to outperform other isolation techniques in speed, purity and yield. We demonstrated EXODUS by purifying exosomes from urine samples of 113 patients and validated the practical relevance in exosomal RNA profiling with the high-resolution capability and high-throughput analysis.

The genetic source tracking of human urinary exosomes.

The genetic origins of nanoscale extracellular vesicles in our body fluids remains unclear. Here, we perform a tracking analysis of urinary exosomes via RNA sequencing, revealing that urine exosomes mostly express tissue-specific genes for the bladder and have close cell-genetic relationships to the endothelial cell, basal cell, monocyte, and dendritic cell. Tracking the differentially expressed genes of cancers and corresponding enrichment analysis show urine exosomes are intensively involved in immune activities, indicating that they may be harnessed as reliable biomarkers of noninvasive liquid biopsy in cancer genomic diagnostics and precision medicine.

Metabolomic investigation of urinary extracellular vesicles for early detection and screening of lung cancer.

Lung cancer is a prevalent cancer type worldwide that often remains asymptomatic in its early stages and is frequently diagnosed at an advanced stage with a poor prognosis due to the lack of effective diagnostic techniques and molecular biomarkers. However, emerging evidence suggests that extracellular vesicles (EVs) may promote lung cancer cell proliferation and metastasis, and modulate the anti-tumor immune response in lung cancer carcinogenesis, making them potential biomarkers for early cancer detection. To investigate the potential of urinary EVs for non-invasive detection and screening of patients at early stages, we studied metabolomic signatures of lung cancer. Specifically, we conducted metabolomic analysis of 102 EV samples and identified metabolome profiles of urinary EVs, including organic acids and derivatives, lipids and lipid-like molecules, organheterocyclic compounds, and benzenoids. Using machine learning with a random forest model, we screened for potential markers of lung cancer and identified a marker panel consisting of Kanzonol Z, Xanthosine, Nervonyl carnitine, and 3,4-Dihydroxybenzaldehyde, which exhibited a diagnostic potency of 96% for the testing cohort (AUC value). Importantly, this marker panel also demonstrated effective prediction for the validation set, with an AUC value of 84%, indicating the reliability of the marker screening process. Our findings suggest that the metabolomic analysis of urinary EVs provides a promising source of non-invasive markers for lung cancer diagnostics. We believe that the EV metabolic signatures could be used to develop clinical applications for the early detection and screening of lung cancer, potentially improving patient outcomes.

The invisible Threat: Assessing the reproductive and transgenerational impacts of micro- and nanoplastics on fish.

Micro- and nanoplastics (MNPs), emerging as pervasive environmental pollutants, present multifaceted threats to diverse ecosystems. This review critically examines the ability of MNPs to traverse biological barriers in fish, leading to their accumulation in gonadal tissues and subsequent reproductive toxicity. A focal concern is the potential transgenerational harm, where offspring not directly exposed to MNPs exhibit toxic effects. Characterized by extensive specific surface areas and marked surface hydrophobicity, MNPs readily adsorb and concentrate other environmental contaminants, potentially intensifying reproductive and transgenerational toxicity. This comprehensive analysis aims to provide profound insights into the repercussions of MNPs on fish reproductive health and progeny, highlighting the intricate interplay between MNPs and other pollutants. We delve into the mechanisms of MNPs-induced reproductive toxicity, including gonadal histopathologic alterations, oxidative stress, and disruptions in the hypothalamic-pituitary-gonadal axis. The review also underscores the urgency for future research to explore the size-specific toxic dynamics of MNPs and the long-term implications of chronic exposure. Understanding these aspects is crucial for assessing the ecological risks posed by MNPs and formulating strategies to safeguard aquatic life.

Exploring the potential of white birch sap: A natural alternative to traditional skin whitening agents with reduced side effects.

Common tyrosinase (TYR) inhibitors used in cosmetics, such as hydroquinone, kojic acid, and arbutin, can cause side effects including erythema, skin peeling, and dryness. Therefore, the development of natural whitening agents that offer excellent permeability, minimal irritation, and high safety has become a primary focus in the field of TYR inhibitors. In this study, we demonstrate that White birch sap (WBS), within a safe concentration range, effectively reduces TYR activity and melanin content in both B16F10 mouse melanoma cells and zebrafish larvae. Importantly, WBS exhibits minimal irritation to neutrophils in fluorescent zebrafish and does not affect the behavior of adult zebrafish. Furthermore, WBS downregulates the gene expression levels of microphthalmia-associated transcription factor, TYR, tyrosinase-related protein-1, and tyrosinase-related protein-2 in B16F10 cells. In conclusion, our research confirms that WBS, a naturally derived substance, offers high safety and mild effects, making it a promising candidate for a skin-whitening agent.

Engineered Cell Membrane-Coated Nanoparticles: New Strategies in Glioma Targeted Therapy and Immune Modulation.

Gliomas, the most prevalent primary brain tumors, pose considerable challenges due to their heterogeneity, intricate tumor microenvironment (TME), and blood-brain barrier (BBB), which restrict the effectiveness of traditional treatments like surgery and chemotherapy. This review provides an overview of engineered cell membrane technologies in glioma therapy, with a specific emphasis on targeted drug delivery and modulation of the immune microenvironment. This study investigates the progress in engineered cell membranes, encompassing physical, chemical, and genetic alterations, to improve drug delivery across the BBB and effectively target gliomas. The examination focuses on the interaction of engineered cell membrane-coated nanoparticles (ECM-NPs) with the TME in gliomas, emphasizing their potential to modulate glioma cell behavior and TME to enhance therapeutic efficacy. The review further explores the involvement of ECM-NPs in immunomodulation techniques, highlighting their impact on immune reactions. While facing obstacles related to membrane stability and manufacturing scalability, the review outlines forthcoming research directions focused on enhancing membrane performance. This review underscores the promise of ECM-NPs in surpassing conventional therapeutic constraints, proposing novel approaches for efficacious glioma treatment.

Behavioral Studies of Zebrafish Reveal a New Perspective on the Reproductive Toxicity of Micro- and Nanoplastics.

The escalating prevalence of microplastics and nanoplastics in aquatic environments is a major challenge affecting the behavior and reproductive health of aquatic organisms while posing potential risks to human health and ecosystems. This review focuses on the neurobehavioral changes and reproductive toxicity of MNPs in zebrafish and their relationships. At the same time, the neurobehavioral changes caused by MNPs were studied, and the synergistic effects of the interaction of these pollutants with other environmental contaminants were explored. In addition, zebrafish, as a model organism, provide valuable insights into the subtle but important effects of MNPs on reproductive behavior, which is critical for understanding reproductive success, suggesting that behavioral changes can serve as an early biomarker of reproductive toxicity. In addition, based on classical endocrine disruptor models and behavioral research methods, the current status of the research on the reproductive toxicity of MNPs in zebrafish was reviewed, which further indicated that the behavioral parameters of zebrafish can be used as an effective and rapid tool to evaluate the reproductive toxicity of MNPs. However, behavioral methods for rapidly assessing the toxicity of MNPs are still an area of exploration. To address limitations and challenges in the current scope of research, this review outlines future research directions with the aim of improving our understanding of the environmental and health impacts of MNPs. This work aims to inform targeted environmental policies and advance public health strategies to address the growing challenge of MNPs pollution.

Rapid altitude displacement induce zebrafish appearing acute high altitude illness symptoms.

Rapid ascent to high-altitude areas above 2500 m often leads to acute high altitude illness (AHAI), posing significant health risks. Current models for AHAI research are limited in their ability to accurately simulate the high-altitude environment for drug screening. Addressing this gap, a novel static self-assembled water vacuum transparent chamber was developed to induce AHAI in zebrafish. This study identified 6000 m for 2 h as the optimal condition for AHAI induction in zebrafish. Under these conditions, notable behavioral changes including slow movement, abnormal exploration behavior and static behavior in the Novel tank test. Furthermore, this model demonstrated changes in oxidative stress-related markers included increased levels of malondialdehyde, decreased levels of glutathione, decreased activities of superoxide dismutase and catalase, and increased levels of inflammatory markers IL-6, IL-1ß and TNF-α, and inflammatory cell infiltration and mild edema in the gill tissue, mirroring the clinical pathophysiology observed in AHAI patients. This innovative zebrafish model not only offers a more accurate representation of the high-altitude environment but also provides a high-throughput platform for AHAI drug discovery and pathogenesis research.

Cell membrane nanomaterials composed of phospholipids and glycoproteins for drug delivery in inflammatory bowel disease: A review.

Inflammatory bowel disease (IBD) is a serious chronic intestinal disorder with an increasing global incidence. However, current treatment strategies, such as anti-inflammatory drugs and probiotics, have limitations in terms of safety, stability, and effectiveness. The emergence of targeted nanoparticles has revolutionized IBD treatment by enhancing the biological properties of drugs and promoting efficiency and safety. Unlike synthetic nanoparticles, cell membrane nanomaterials (CMNs) consist primarily of biological macromolecules, including phospholipids, proteins, and sugars. CMNs include red blood cell membranes, macrophage membranes, and leukocyte membranes, which possess abundant glycoprotein receptors and ligands on their surfaces, allowing for the formation of cell-to-cell connections with other biological macromolecules. Consequently, they exhibit superior cell affinity, evade immune responses, and target inflammation effectively, making them ideal material for targeted delivery of IBD therapies. This review explores various CMNs delivery systems for IBD treatment. However, due to the complexity and harsh nature of the intestinal microenvironment, the lack of flexibility or loss of selectivity poses challenges in designing single CMNs delivery strategies. Therefore, we propose a hierarchically programmed delivery modality that combines CMNs with pH, charge, ROS and ligand-modified responsive nanoparticles. This approach significantly improves delivery efficiency and points the way for future research in this area.

Advances in Escherichia coli Nissle 1917 as a customizable drug delivery system for disease treatment and diagnosis strategies.

With the in-depth and comprehensive study of bacteria and their related ecosystems in the human body, bacterial-based drug delivery system has become an emerging biomimetic platform that can retain the innate biological functions. Benefiting from its good biocompatibility and ideal targeting ability as a biological carrier, Escherichia coli Nissle 1917 (ECN) has been focused on the treatment strategies of inflammatory bowel disease and tumor. The advantage of a bacterial carrier is that it can express exogenous protein while also acting as a natural capsule by releasing drug slowly as a result of its own colonization impact. In order to survive in harsh environments such as the digestive tract and tumor microenvironment, ECN can be modified or genetically engineered to enhance its function and host adaptability. The adoption of ECN carries or expresses drugs which are essential for accurate diagnosis and treatment. This review briefly describes the properties of ECN, the relationship between ECN and inflammation and tumor, and the strategy of using surface modification and genetic engineering to modify ECN as a delivery carrier for disease treatment.

Improvement in Zebrafish with Diabetes and Alzheimer's Disease Treated with Pasteurized Akkermansia muciniphila.

Diabetes and Alzheimer's disease (AD) are associated with specific changes in the composition of the intestinal flora. Studies have shown that the supplementation with pasteurized Akkermansia muciniphila has therapeutic and preventive effects on diabetes. However, it is not clear whether there is any association with improvement in and prevention of Alzheimer's disease and diabetes with Alzheimer's disease. Here, we found that pasteurized Akkermansia muciniphila can significantly improve the blood glucose, body mass index, and diabetes indexes of zebrafish with diabetes mellitus complicated with Alzheimer's disease and also alleviate the related indexes of Alzheimer's disease. The memory, anxiety, aggression, and social preference behavior of zebrafish with combined type 2 diabetes mellitus (T2DM) and Alzheimer's disease (TA zebrafish) were significantly improved after pasteurized Akkermansia muciniphila treatment. Moreover, we examined the preventive effect of pasteurized Akkermansia muciniphila on diabetes mellitus complicated with Alzheimer's disease. The results showed that the zebrafish in the prevention group were better in terms of biochemical index and behavior than the zebrafish in the treatment group. These findings provide new ideas for the prevention and treatment of diabetes mellitus complicated with Alzheimer's disease. IMPORTANCE The interaction between intestinal microflora and host affects the progression of diabetes and Alzheimer's disease. As a recognized next-generation probiotic, Akkermansia muciniphila has been shown to play a key role in the progression of diabetes and Alzheimer's disease, but whether A. muciniphila can improve diabetes complicated with Alzheimer's disease and its potential mechanism are unclear. In this study, a new zebrafish model of diabetes mellitus complicated with Alzheimer's disease was established, and the effect of Akkermansia muciniphila on diabetes mellitus complicated with Alzheimer's disease is discussed. The results showed that Akkermansia muciniphila after pasteurization significantly improved and prevented diabetes mellitus complicated with Alzheimer's disease. Treatment with pasteurized Akkermansia muciniphila improved the memory, social preference, and aggressive and anxiety behavior of TA zebrafish and alleviated the pathological characteristics of T2DM and AD. These results provide a new prospect for probiotics in the treatment of diabetes and Alzheimer's disease.

Hand Sanitizer Gels: Classification, Challenges, and the Future of Multipurpose Hand Hygiene Products.

Hand hygiene is a crucial measure in the prevention and control of infections, and there is a growing awareness among individuals who are making a conscious effort to maintain hand cleanliness. With the advent of the SARS-CoV-2 outbreak, the demand for hand hygiene products has also gradually shifted towards those with antimicrobial properties. Among these products, hand sanitizer gels (HSGs) have gained considerable popularity as an efficient method of hand cleaning, due to their rapid drying and sustained antimicrobial efficacy. Concurrently, there has been a growing interest in novel HSGs that offer additional functions such as skin whitening, moisturizing, and anti-inflammatory effects. These novel HSGs effectively address concerns associated with the ingestion of antimicrobial ingredients and demonstrate reduced skin irritation, thereby alleviating hand dermatological issues. This review provides an extensive overview of the application scenarios, classification, and challenges associated with HSGs while emphasizing the emergence of novel components with biological functions, aiming to contribute to the advancement of hand hygiene practices and offer novel insights for the development of novel HSGs with outstanding antimicrobial properties with other multiple biological functions and desirable biosafety profiles.

Rapid Assessment of Ocular Toxicity from Environmental Contaminants Based on Visually Mediated Zebrafish Behavior Studies.

The presence of contaminants in the environment has increased in recent years, and studies have demonstrated that these contaminants have the ability to penetrate the blood-retinal barrier and directly affect the visual systems of organisms. Zebrafish are recognized as an ideal model for human eye diseases due to their anatomical and functional similarities to the human eye, making them an efficient and versatile organism for studying ocular toxicity caused by environmental contaminants in the field of environmental toxicology. Meanwhile, zebrafish exhibit a diverse repertoire of visually mediated behaviors, and their visual system undergoes complex changes in behavioral responses when exposed to environmental contaminants, enabling rapid assessment of the ocular toxicity induced by such pollutants. Therefore, this review aimed to highlight the effectiveness of zebrafish as a model for examining the effects of environmental contaminants on ocular development. Special attention is given to the visually mediated behavior of zebrafish, which allows for a rapid assessment of ocular toxicity resulting from exposure to environmental contaminants. Additionally, the potential mechanisms by which environmental contaminants may induce ocular toxicity are briefly outlined.

The role of hydrogen therapy in Alzheimer's disease management: Insights into mechanisms, administration routes, and future challenges.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder predominantly affecting the elderly. While conventional pharmacological therapies remain the primary treatment for AD, their efficacy is limited effectiveness and often associated with significant side effects. This underscores the urgent need to explore alternative, non-pharmacological interventions. Oxidative stress has been identified as a central player in AD pathology, influencing various aspects including amyloid-beta metabolism, tau phosphorylation, autophagy, neuroinflammation, mitochondrial dysfunction, and synaptic dysfunction. Among the emerging non-drug approaches, hydrogen therapy has garnered attention for its potential in mitigating these pathological conditions. This review provides a comprehensively overview of the therapeutic potential of hydrogen in AD. We delve into its mechanisms of action, administration routes, and discuss the current challenges and future prospects, with the aim of providing valuable insights to facilitate the clinical application of hydrogen-based therapies in AD management.

Escherichia coli Nissle 1917 ghosts alleviate inflammatory bowel disease in zebrafish.

Escherichia coli Nissle 1917 (EcN) has become a research hotspot in inflammatory bowel disease (IBD). It has a strong targeting effect on the colon, and has some therapeutic effect on inflammatory bowel disease. EcN is prepared into EcN ghosts, which also retain EcN's biological characteristics. Consequently, EcN ghosts are used for drug delivery. This study evaluated the safety and efficacy of EcN ghosts as carriers of drugs for treating IBD in zebrafish. Caco-2 cell adhesion experiments and zebrafish intestinal adhesion experiments demonstrated that EcN ghosts was highly adherent to the intestine. Additionally, oral administration of EcN ghosts attenuated dextran sulfate sodium-induced IBD symptoms by inhibiting neutrophil chemotaxis and reactive oxygen species production in larval zebrafish. Because of the unique biological functions of EcN ghosts, it may serve as a strategy for future targeted drug delivery in IBD treatment.

Microbiota-Gut-Brain Axis Dysregulation in Alzheimer's Disease: Multi-Pathway Effects and Therapeutic Potential.

An essential regulator of neurodegenerative conditions like Alzheimer's disease (AD) is the gut microbiota. Alterations in intestinal permeability brought on by gut microbiota dysregulation encourage neuroinflammation, central immune dysregulation, and peripheral immunological dysregulation in AD, as well as hasten aberrant protein aggregation and neuronal death in the brain. However, it is unclear how the gut microbiota transmits information to the brain and how it influences brain cognition and function. In this review, we summarized the multiple pathways involved in the gut microbiome in AD and provided detailed treatment strategies based on the gut microbiome. Based on these observations, this review also discusses the problems, challenges, and strategies to address current therapeutic strategies.

Biological Functions and Applications of Antimicrobial Peptides.

Despite antimicrobial resistance, which is attributed to the misuse of broad-spectrum antibiotics, antibiotics can indiscriminately kill pathogenic and beneficial microorganisms. These events disrupt the delicate microbial balance in both humans and animals, leading to secondary infections and other negative effects. Antimicrobial peptides (AMPs) are functional natural biopolymers in plants and animals. Due to their excellent antimicrobial activities and absence of microbial resistance, AMPs have attracted enormous research attention. We reviewed the antibacterial, antifungal, antiviral, antiparasitic, as well as antitumor properties of AMPs and research progress on AMPs. In addition, we highlighted various recommendations and potential research areas for their progress and challenges in practical applications.

Research progress on extraction technology and biomedical function of natural sugar substitutes.

Improved human material living standards have resulted in a continuous increase in the rate of obesity caused by excessive sugar intake. Consequently, the number of diabetic patients has skyrocketed, not only resulting in a global health problem but also causing huge medical pressure on the government. Limiting sugar intake is a serious problem in many countries worldwide. To this end, the market for sugar substitute products, such as artificial sweeteners and natural sugar substitutes (NSS), has begun to rapidly grow. In contrast to controversial artificial sweeteners, NSS, which are linked to health concepts, have received particular attention. This review focuses on the extraction technology and biomedical function of NSS, with a view of generating insights to improve extraction for its large-scale application. Further, we highlight research progress in the use of NSS as food for special medical purpose (FSMP) for patients.

Advances in lncRNAs from stem cell-derived exosome for the treatment of cardiovascular diseases.

Cardiovascular diseases (CVDs) are the leading cause of mortality globally. Benefiting from the advantages of early diagnosis and precision medicine, stem cell-based therapies have emerged as promising treatment options for CVDs. However, autologous or allogeneic stem cell transplantation imposes a potential risk of immunological rejection, infusion toxicity, and oncogenesis. Fortunately, exosome can override these limitations. Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) in exosome from stem cell paracrine factors play critical roles in stem cell therapy and participate in numerous regulatory processes, including transcriptional silencing, transcriptional activation, chromosome modification, and intranuclear transport. Accordingly, lncRNAs can treat CVDs by directly acting on specific signaling pathways. This mini review systematically summarizes the key regulatory actions of lncRNAs from different stem cells on myocardial aging and apoptosis, ischemia-reperfusion injury, retinopathy, atherosclerosis, and hypertension. In addition, the current challenges and future prospects of lncRNAs treatment for CVDs are discussed.

Effect of aerobic exercise as a treatment on type 2 diabetes mellitus with depression-like behavior zebrafish.

BACKGROUND: Depression is the most known complication of type 2 diabetes mellitus (T2DM). Aerobic exercise improves glycemic control in T2DM, although the underlying mechanisms of comorbid depression-like behaviors in T2DM have not yet been fully elucidated. METHODS: 120 zebrafish were randomly assigned to four groups: Control, T2DM, T2DM + metformin, and T2DM + aerobic exercise. Then, all animals except the control group were fed with high glucose fairy shrimp (~40 g/kg/day) and exposed reserpine (40 µg/ml for 20 min) for 10 days. Here, behavioral tests were used for model verification. Following the verification, all groups were treated as before. Additionally, the T2DM + metformin group received metformin (~10.6 mg/kg/day) at the same time, while the T2DM + aerobic exercise group received aerobic exercise 30 min/day. Finally, blood glucose and behavioral tests, as well as protein and molecular levels were determined at Day 11 and 12. RESULTS: Aerobic exercise alleviated depressive-like behavior and enhanced the levels of antidepressant biomarkers (NE, 5-HIAA) in zebrafish after 10 consecutive days of exercise. Additionally, 10 consecutive days of aerobic exercise decreased the levels of inflammatory biomarkers (IFN-γ, IL-1, IL-4) and depressive biomarkers (cortisol). Meanwhile, it also aided in the reduction of CD11b, IL-6, IL-6R, and caspase-3 expression to combat the neuroinflammation induced by T2DM, mediated the BDNF-TrkB pathway, and increased Bcl-2/Bax levels. CONCLUSION: Given the remarkable similarity in neurochemistry between humans and zebrafish, this study supports the effectiveness of aerobic exercise as clinical guidance in preventing and treating T2DM complicated with depression.