Nanoparticle-Based Drug Delivery Systems: An Inspiring Therapeutic Strategy for Neurodegenerative Diseases.

Neurodegenerative diseases are common, incurable neurological disorders with high prevalence, and lead to memory, movement, language, and intelligence impairments, threatening the lives and health of patients worldwide. The blood-brain barrier (BBB), a physiological barrier between the central nervous system and peripheral blood circulation, plays an important role in maintaining the homeostasis of the intracerebral environment by strictly regulating the transport of substances between the blood and brain. Therefore, it is difficult for therapeutic drugs to penetrate the BBB and reach the brain, and this affects their efficacy. Nanoparticles (NPs) can be used as drug transport carriers and are also known as nanoparticle-based drug delivery systems (NDDSs). These systems not only increase the stability of drugs but also facilitate the crossing of drugs through the BBB and improve their efficacy. In this article, we provided an overview of the types and administration routes of NPs, highlighted the preclinical and clinical studies of NDDSs in neurodegenerative diseases, and summarized the combined therapeutic strategies in the management of neurodegenerative diseases. Finally, the prospects and challenges of NDDSs in recent basic and clinical research were also discussed. Above all, NDDSs provide an inspiring therapeutic strategy for the treatment of neurodegenerative diseases.

Fucoidan ameliorates LPS-induced neuronal cell damage and cognitive impairment in mice.

The incidence of cognitive impairment is rising globally, but there is no effective therapy. Recent studies showed that fucoidan (Fuc), a sulfated polysaccharide enriched in brown algae, is widely used due to its anti-inflammatory, antioxidant, and prebiotic effects. However, the effects and mechanisms of Fuc on lipopolysaccharide (LPS)-induced neuronal cell damage and cognitive impairment in mice need to be explored further. In the present study, we found that Fuc treatment protected HT22 cells from LPS-induced damage by inhibiting the activation of NLRP3 inflammasomes. Fuc exerted neuroprotective effects in mice with LPS-induced cognitive impairment by ameliorating neuroinflammation, promoting neurogenesis, and reducing blood-brain barrier and intestinal barrier permeability. Mechanistically, Fuc supplement significantly restructured the gut microbiota composition, which may be related to glucose and fructose metabolism. In conclusion, Fuc ameliorated LPS-induced neuronal cell damage and cognitive impairment in mice, suggesting that Fuc may be a medicinal and food homologous functional agent to improve cognitive function.

Applications and Mechanisms of Stimuli-Responsive Hydrogels in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a global neurotrauma with high morbidity and mortality that seriously threatens the life quality of patients and causes heavy burdens to families, healthcare institutions, and society. Neuroinflammation and oxidative stress can further aggravate neuronal cell death, hinder functional recovery, and lead to secondary brain injury. In addition, the blood-brain barrier prevents drugs from entering the brain tissue, which is not conducive to the recovery of TBI. Due to their high water content, biodegradability, and similarity to the natural extracellular matrix (ECM), hydrogels are widely used for the delivery and release of various therapeutic agents (drugs, natural extracts, and cells, etc.) that exhibit beneficial therapeutic efficacy in tissue repair, such as TBI. Stimuli-responsive hydrogels can undergo reversible or irreversible changes in properties, structures, and functions in response to internal/external stimuli or physiological/pathological environmental stimuli, and further improve the therapeutic effects on diseases. In this paper, we reviewed the common types of stimuli-responsive hydrogels and their applications in TBI, and further analyzed the therapeutic effects of hydrogels in TBI, such as pro-neurogenesis, anti-inflammatory, anti-apoptosis, anti-oxidation, and pro-angiogenesis. Our study may provide strategies for the treatment of TBI by using stimuli-responsive hydrogels.

Porous magnetic carbon CoFe alloys@ZnO@C composites based on Zn/Co-based bimetallic MOF with efficient electromagnetic wave absorption.

To obtain lightweight and efficient electromagnetic wave absorbing materials, Fe2O3@ZnCo-MOF composites were prepared in this paper by in-situ growth method, and CoFe alloys@ZnO@C composites were obtained by subsequent annealing process. By varying the loading of Fe2O3 during the synthesis process, a series of composites were obtained. Among them, CoFe alloys@ZnO@C-0.1 has the best electromagnetic wave absorption performance, which can reach a reflection loss (RL) of -40.63 dB at a thickness of 2.2 mm, while the reflection loss is -44.13 dB at a thickness of 5.0 mm, and the maximum effective absorption bandwidth (EAB) is 5.84 GHz at a thickness of 2.4 mm. The excellent performance can be attributed to the synergistic effect of the dielectric and magnetic properties of the composites as well as the effective impedance matching properties. Thus, the CoFe alloys@ZnO@C composite is expected to be a lightweight and efficient material for electromagnetic wave absorption.

Establishment of universal human embryonic stem cell lines.

The potential application of human embryonic stem cells in regenerative medicine using cell, tissue or organ transplantation has aroused great interest. However, HLA incompatibility between donor cells or tissues and the recipient is a primary obstacle to the use of unmatched human embryonic stem cells and their derivatives as donor 'grafts' for patient treatment without some form of immunosuppressive therapy. This is because, for most tissues, which express HLA Class I antigens, the recipient patient's immune system will recognize the difference between their and the donor's HLA types, leading to graft rejection in the absence of immunosuppressive therapy. One approach to overcoming this obstacle and enabling the use of a single or limited range of suitably selected human embryonic stem cells and their derivatives without needing extensive HLA matching is to use gene-editing technology to establish a universally or widely HLA compatible human embryonic stem cell line, thereby providing a potentially unlimited source of cells for future cell, tissue or organ transplantation. This article reviews current strategies and methods for establishing such universal or near universally HLA compatible human embryonic stem cell lines.

Generation of NERCe003-A-3, a p53 compound heterozygous mutation human embryonic stem cell line, by CRISPR/Cas9 editing.

p53 is a tumor suppressor gene involved mainly in the regulation of the G1/S cell cycle phase, DNA repair, and senescence. Although p53 is frequently altered in human cancer, the consequences of its depletion in human embryonic stem cells (hESCs) are unknown. We generated NERCe003-A-3, a p53 knockout hESC line, from the normal NERCe003-A hESC line by using CRISPR/Cas9 editing. This cell line maintained a normal 46, XY karyotype. Further analysis suggested that the cells expressed pluripotency-related markers and had the capacity to differentiate in vitro into derivatives of all three germ layers.