UNASSIGNED: Exosomes, a type of extracellular vesicles, are effective tools for delivering small-molecule drugs and biological therapeutics into cells and tissues. Surface modifications with targeting ligands ensure precise delivery to specific cells, minimizing accumulation in healthy organs and reducing the side effects. This is a rapidly growing area in drug delivery research and this review aims to comprehensively discuss the recent advances in the field.
UNASSIGNED: Recent studies have presented compelling evidence supporting the application of exosomes as efficient delivery vehicles that escape endosome trapping, achieving effective in vivo delivery in animal models. This review provides a systemic discussion on the exosome-based delivery technology, with topics covering exosome purification, surface modification, and targeted delivery of various cargos ranging from siRNAs, miRNAs, and proteins, to small molecule drugs.
UNASSIGNED: Exosome-based gene and drug delivery has low toxicity and low immunogenicity. Surface modifications of the exosomes can effectively avoid endosome trapping and increase delivery efficiency. This exciting technology can be applied to improve the treatments for a wide variety of diseases.

Endosomal sorting complex required for transport (ESCRT) system drives various cellular processes, including endosome sorting, organelle biogenesis, vesicle transport, maintenance of plasma membrane integrity, membrane fission during cytokinesis, nuclear membrane reformation after mitosis, closure of autophagic vacuoles, and enveloped virus budding. Increasing evidence suggests that the ESCRT system can be hijacked by different family viruses for their proliferation. At different stages of the virus life cycle, viruses can interfere with or exploit ESCRT-mediated physiological processes in various ways to maximize their chance of infecting the host. In addition, many retroviral and RNA viral proteins possess \"late domain\" motifs, which can recruit host ESCRT subunit proteins to assist in virus endocytosis, transport, replicate, budding and efflux. Therefore, the \"late domain\" motifs of viruses and ESCRT subunit proteins could serve as promising drug targets in antiviral therapy. This review focuses on the composition and functions of the ESCRT system, the effects of ESCRT subunits and virus \"late domain\" motifs on viral replication, and the antiviral effects mediated by the ESCRT system, aiming to provide a reference for the development and utilization of antiviral drugs.

Nanotechnology is the use of materials that have unique nanoscale properties. In recent years, nanotechnologies have shown promising results for human health, especially in cancer treatment. The self-assembly characteristic of RNA is a powerful bottom-up approach to the design and creation of nanostructures through interdisciplinary biological, chemical and physical techniques. The use of RNA nanotechnology in therapeutics is about to be realized. This review discusses different kinds of nano-based drug delivery systems and their characteristic features.
A branch of nanotechnology called RNA nanotechnology involves designing, studying, and utilizing synthetic structures based on RNA. This review discusses different kinds of nano-based drug delivery systems and their characteristic features. It aims to provide an overview of nanoparticles as a delivery system for gene therapy to treat diseases such as cancer. In order to enhance nanoparticle efficacy, these systems should be designed with this in mind in order to develop and test delivery systems rationally and scientifically.

Small extracellular vesicles (sEVs), a subset of extracellular vesicles (EVs) originating from the endosomal compartment, are a kind of lipid bilayer vesicles released by almost all types of cells, serving as natural carriers of nucleic acids, proteins, and lipids for intercellular communication and transfer of bioactive molecules. The current findings suggest their vital role in physiological and pathological processes. Various sEVs labeling techniques have been developed for the more advanced study of the function, mode of action, bio-distribution, and related information of sEVs. In this review, we summarize the existing and emerging sEVs labeling techniques, including fluorescent labeling, radioisotope labeling, nanoparticle labeling, chemical contrast agents labeling, and label-free technique. These approaches will pave the way for an in-depth study of sEVs. We present a systematic and comprehensive review of the principles, advantages, disadvantages, and applications of these techniques, to help promote applications of these labeling approaches in future research on sEVs.

Fluorescent labeling of vesicular structures in cultured cells, particularly for live cells, can be challenging for a number of reasons. The first challenge is to identify a reagent that will be specific enough where some structures have a number of potential reagents and others very few options. The emergence of BacMam constructs has provided more easy-to-use choices. Presented here is a discussion of BacMam constructs as well as a review of commercially available reagents for labeling vesicular structures in cells, including endosomes, peroxisomes, lysosomes, and autophagosomes, complete with a featured reagent, recommended protocol, troubleshooting guide, and example image for each structure. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Delivering targeted fluorescent proteins using pre-made, high-titer BacMam constructs Alternate Protocol 1: Non-pseudo-typed BacMam viruses in standard cell types and pseudo-typed BacMam viruses in hard-to-transduce cell types Basic Protocol 2: Labeling endosomes: pHrodo™-10k-dextran Basic Protocol 3: Labeling peroxisomes: BacMam 2.0 CellLight™ Peroxisome-GFP Alternate Protocol 2: Labeling peroxisomes using antibodies Basic Protocol 4: Labeling autophagosomes: Transduction of cells with Premo™ Autophagy Sensor GFP-LC3B Alternate Protocol 3: Labeling autophagosomes using antibodies Basic Protocol 5: Labeling lysosomes: LysoTracker Red DND-99.

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The endosomal-lysosomal and autophagy (ELA) pathway may be implicated in the progression of Alzheimer\'s disease (AD); however, findings thus far have been inconsistent.
To systematically summarize differences in endosomal-lysosomal and autophagy proteins in the cerebrospinal fluid (CSF) of people with AD and healthy controls (HC).
Studies measuring CSF concentrations of relevant proteins in the ELA pathway in AD and healthy controls were included. Standardized mean differences (SMD) with 95% confidence intervals (CI) between AD and healthy controls in CSF concentrations of relevant proteins were meta-analyzed using random-effects models.
Of 2,471 unique studies, 43 studies were included in the systematic review and meta-analysis. Differences in ELA protein levels in the CSF between AD and healthy controls were observed, particularly in lysosomal membrane (LAMP-1: NAD/NHC = 348/381, SMD [95% CI] = 0.599 [0.268, 0.930], I2 = 72.8%; LAMP-2: NAD/NHC = 401/510, SMD [95% CI] = 0.480 [0.134, 0.826], I2 = 78.7%) and intra-lysosomal proteins (GM2A: NAD/NHC = 390/420, SMD [95% CI] = 0.496 [0.039, 0.954], I2 = 87.7%; CTSB: NAD/NHC = 485/443, SMD [95% CI] = 0.201 [0.029, 0.374], I2 = 28.5%; CTSZ: NAD/NHC = 535/820, SMD [95% CI] = -0.160 [-0.305, -0.015], I2 = 24.0%) and in proteins involved in endocytosis (AP2B1:NAD/NHC = 171/205, SMD [95% CI] = 0.513 [0.259, 0.768], I2 = 27.4%; FLOT1: NAD/NHC = 41/45, SMD [95% CI] = -0.489 [-0.919, -0.058], I2 <0.01). LC3B, an autophagy marker, also showed a difference (NAD/NHC = 70/59, SMD [95% CI] = 0.648 [0.180, 1.116], I2 = 38.3%)), but overall there was limited evidence suggesting differences in proteins involved in endosomal function and autophagy.
Dysregulation of proteins in the ELA pathway may play an important role in AD pathogenesis. Some proteins within this pathway may be potential biomarkers for AD.

G protein‑coupled receptors (GPCRs) are the largest family of membrane receptors and activate several downstream signaling pathways involved in numerous physiological cellular processes. GPCRs are usually internalized and desensitized by intracellular signals. Numerous studies have shown that several GPCRs interact with sorting nexin 27 (SNX27), a cargo selector of the retromer complex, and are recycled from endosomes to the plasma membrane. Recycled GPCRs usually contain specific C‑terminal postsynaptic density protein 95/Discs large protein/Zonula occludens 1 (PDZ) binding motifs, which are specifically recognized by SNX27, and return to the cell surface as functionally naïve receptors. Aberrant endosome‑to‑membrane recycling of GPCRs mediated by SNX27 may serve a critical role in cancer growth and development. Therefore, SNX27 may be a novel target for cancer therapies.

Long non‑coding RNAs (lncRNAs) comprise a sizeable class of non‑coding RNAs with a length of over 200 base pairs. Little is known about their biological function, although over 20,000 lncRNAs have been annotated in the human genome. Through a diverse range of mechanisms, their primary function is in the regulation of the transcription of protein‑coding genes. lncRNA transcriptional activation can result from a group of nucleus‑retained and chromatin‑associated lncRNAs, which function as scaffolds in the cis/trans recruitment of transcription factors, co‑activators or chromatin remodelers, and/or promoter enhancers. Exosomes are released as extracellular vesicles and they are produced by endocytic pathways. Their synthesis is initiated by various processes including ceramide synthesis, release of intracellular Ca2+ or acid‑base balance disorders. Prior to vesicle creation, selective cargo loading occurs in the Endosomal Sorting Complex Required for Transport. Participation of endosomal sorting proteins such as tetraspanins or specific sumoylated proteins required for transport has been indicated in research. The endosomal‑sorting complex consists of four components, these induce the formation of multivesicular bodies and the induction of membrane deformation to form exosomes. Nanovesicles could be formed inside multivesicular bodies to allow transport outside the cell or digestion in lysosomes. The molecular content of exosomes is more heterogenic than its synthesis process, with different cargoes being examined inside vesicles with regard to the type or stage of cancers. This paper will review the importance of lncRNAs as crucial molecular content of exosomes, indicating its involvement in tumour suppression, pro‑tumorigenic events and the development of novel therapeutic approaches in the near future. Further studies of their mechanisms of function are essential, as well as overcoming several challenges to gain a clearer insight to the approaches for the best clinical application.

Neurons are long-lived and highly polarized cells that depend on autophagy to maintain cellular homeostasis. The robust, constitutive biogenesis of autophagosomes in the distal axon occurs via a conserved pathway that is required to maintain functional synapses and prevent axon degeneration. Autophagosomes are formed de novo at the axon terminal in a stepwise assembly process, engulfing mitochondrial fragments, aggregated proteins, and bulk cytosol in what appears to be a nonselective uptake mechanism. Following formation, autophagosomes fuse with late endosomes/lysosomes and then are rapidly and efficiently transported along the axon toward the soma, driven by the microtubule motor cytoplasmic dynein. Motile autophagosomes mature to autolysosomes in transit by fusing with additional late endosomes/lysosomes, arriving at the soma as fully competent degradative organelles. Misregulation of neuronal autophagy leads to axonal degeneration and synaptic destabilization, and has been implicated in neurodegenerative diseases including Alzheimer\'s disease, Parkinson\'s disease, Huntington\'s disease, and ALS.