Hybrid exosomes, exosome-like nanovesicles and engineered exosomes for therapeutic applications.

Exosomes are the smallest extracellular vesicles that can be released by practically all cell types, and range in size from 30 nm to 150 nm. As the major marker of liquid biopsies, exosomes have great potential for disease diagnosis, therapy, and prognosis. However, their inherent heterogeneity, the complexity of biological fluids, and the presence of nanoscale contaminants make the isolation of exosomes a great challenge. Traditional isolation methods of exosomes are cumbersome and challenging with complex and time-consuming operations. In recent years, the emergence of microfluidic chips, nanolithography, electro-deposition, and other technologies has promoted the combination and innovation of the isolation methods. The application of these methods has brought very considerable benefits to the isolation of exosomes such as ultra-fast, portable integration, and low loss. There are significant functional improvements in isolation yield, isolation purity, and clinical applications. In this review, a series of methods for the isolation of exosomes are summarized, with emphasis on the emerging methods, and in-depth comparison and analysis of each method are provided, including their principles, merits, and demerits.

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Recent developments in isolating methods for exosomes

Oxidative stress (OS) disrupts the chemical integrity of macromolecules and increases the risk of neurodegenerative diseases. Fisetin is a flavonoid that exhibits potent antioxidant properties and protects the cells against OS. We have viewed the NCBI database, PubMed, Science Direct (Elsevier), Springer-Nature, ResearchGate, and Google Scholar databases to search and collect relevant articles during the preparation of this review. The search keywords are OS, neurodegenerative diseases, fisetin, etc. High level of ROS in the brain tissue decreases ATP levels, and mitochondrial membrane potential and induces lipid peroxidation, chronic inflammation, DNA damage, and apoptosis. The subsequent results are various neuronal diseases. Fisetin is a polyphenolic compound, commonly present in dietary ingredients. The antioxidant properties of this flavonoid diminish oxidative stress, ROS production, neurotoxicity, neuro-inflammation, and neurological disorders. Moreover, it maintains the redox profiles, and mitochondrial functions and inhibits NO production. At the molecular level, fisetin regulates the activity of PI3K/Akt, Nrf2, NF-κB, protein kinase C, and MAPK pathways to prevent OS, inflammatory response, and cytotoxicity. The antioxidant properties of fisetin protect the neural cells from inflammation and apoptotic degeneration. Thus, it can be used in the prevention of neurodegenerative disorders. Graphical Abstract

/pdf/the-neuroprotective-effects-of-fisetin-a-natural-flavonoid-3rwt2l14.pdf

The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress

Abstract Synthetic biology aims to design or assemble existing bioparts or bio-components for useful bioproperties. During the past decades, progresses have been made to build delicate biocircuits, standardized biological building blocks and to develop various genomic/metabolic engineering tools and approaches. Medical and pharmaceutical demands have also pushed the development of synthetic biology, including integration of heterologous pathways into designer cells to efficiently produce medical agents, enhanced yields of natural products in cell growth media to equal or higher than that of the extracts from plants or fungi, constructions of novel genetic circuits for tumor targeting, controllable releases of therapeutic agents in response to specific biomarkers to fight diseases such as diabetes and cancers. Besides, new strategies are developed to treat complex immune diseases, infectious diseases and metabolic disorders that are hard to cure via traditional approaches. In general, synthetic biology brings new capabilities to medical and pharmaceutical researches. This review summarizes the timeline of synthetic biology developments, the past and present of synthetic biology for microbial productions of pharmaceutics, engineered cells equipped with synthetic DNA circuits for diagnosis and therapies, live and auto-assemblied biomaterials for medical treatments, cell-free synthetic biology in medical and pharmaceutical fields, and DNA engineering approaches with potentials for biomedical applications. 

/pdf/applications-of-synthetic-biology-in-medical-and-3dkwry2k.pdf

Applications of synthetic biology in medical and pharmaceutical fields

Cadmium sulfide improved with dimanganese copper oxide (Mn2CuO4/CdO) was prepared and applied this semiconductor nanocomposites in advanced oxidative processes via the photoelectrocatalytic efficiency for cephalexin degradation. The Z-scheme Mn2CuO4/CdO nanocomposites was characterized by FESEM, XPS, UV–vis, EIS, and XRD. The photocurrent response were conducted in to evaluate the photo generated in the degradation reaction. Mn2CuO4/CdO was obtained to displays better photoelectrocatalytic response compared to bare CdO; this result shows the role of other semiconductor oxide material as photoanode construction. The degradation of cephalexin in photoelectrocatalytic response is higher than the photocatalytic process. A possible catalysis mechanism was depicted using free radicals scavengers. It was observed that hydroxyl radical and holes contribute as the main role in antibiotic degradation. The Mn2CuO4/CdO was used as great antibacterial agent versus Gram+/−. The Mn2CuO4/CdO probe was used to determine of vitamin B1 in peroxidase activity. The limit of detection was 41.21 nM. 

Multipurpose properties the Z-scheme dimanganese copper oxide/cadmium sulfide nanocomposites for photo- or photoelectro-catalytic, antibacterial applications, and Thiamine detection process

Engineered extracellular vesicles and their mimetics for cancer immunotherapy.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory serine protease synthesized primarily by the liver. It mainly promotes the degradation of low-density lipoprotein receptor (LDL-R) by binding LDL-R, reducing low-density lipoprotein cholesterol (LDL-C) clearance. In addition to regulating LDL-R, PCSK9 inhibitors can also bind Toll-like receptors (TLRs), scavenger receptor B (SR-B/CD36), low-density lipoprotein receptor-related protein 1 (LRP1), apolipoprotein E receptor-2 (ApoER2) and very-low-density lipoprotein receptor (VLDL-R) reducing the lipoprotein concentration and slowing thrombosis. In addition to cardiovascular diseases, PCSK9 is also used in pancreatic cancer, sepsis, and Parkinson’s disease. Currently marketed PCSK9 inhibitors include alirocumab, evolocumab, and inclisiran, as well as small molecules, nucleic acid drugs, and vaccines under development. This review systematically summarized the application, preclinical studies, safety, mechanism of action, and latest research progress of PCSK9 inhibitors, aiming to provide ideas for the drug research and development and the clinical application of PCSK9 in cardiovascular diseases and expand its application in other diseases.

/pdf/pcsk9-inhibition-from-current-advances-to-evolving-future-2goheqiv.pdf

PCSK9 Inhibition: From Current Advances to Evolving Future

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Engineered extracellular vesicles and their mimetics for cancer immunotherapy.

PCSK9 Inhibition: From Current Advances to Evolving Future