The causal role of circulating amino acids on neurodegenerative disorders: A two-sample Mendelian randomization study.

Potential associations between the risk of neurodegenerative diseases and circulating levels of amino acids have been implied in both experimental research and observational studies. However, because of the confounding and reverse causality, the findings could be biased. We aimed to determine whether circulating amino acid levels have potential effects on the risk of neurodegenerative diseases through a more robust analysis. So, we performed a total of two MR analyses, a discovery two-sample MR analysis, and a replication test, using summary-level genome-wide association study (GWAS) data, both with circulating levels of amino acids as exposure and risk of neurodegenerative diseases as an outcome. The potential causalities between nine amino acids (Glutamine [Glu], Leucine [Leu], Isoleucine [Ile], Phenylalanine [Phe], Valine [Val], Alanine [Ala], Tyrosine [Tyr], Histidine [His], and Glycine [Gly]) and six neurodegenerative disorders (Alzheimer's disease [AD], Parkinson's disease [PD], Multiple sclerosis [MS], Frontotemporal dementia [FTD], Lewy body dementia [DLB], Amyotrophic lateral sclerosis [ALS]) were explored in this study. According to the discovery MR analysis, 1 SD. increase in circulating levels of Gln was genetically determined to result in a 13% lower risk of AD (IVW ORSD [95% CI] = 0.872 [0.822, 0.926]; FDR = 7.46 × 10-5 ) while PD risk was decreased to 63% per SD. increase of circulating Leu levels (IVW ORSD [95% CI] = 0.628 [0.467, 0.843]; FDR = 0.021). Results from the replication test provide further evidence of the potential association between circulating Gln levels and AD risk (IVW ORSD [95% CI] = 0.094 [0.028, 0.311]; FDR = 9.98 × 10-4 ). Meanwhile, sensitivity analysis demonstrated that the significant relationships revealed by our two-sample MR outcomes were reliable. Our analyses provided robust evidence of causal associations between circulating levels of Gln and AD risk as well as circulating Leu levels and risk of PD. However, the underlying mechanisms remain to be further investigated.

ECM-Mimicking Hydrogels Loaded with Bone Mesenchymal Stem Cell-Derived Exosomes for the Treatment of Cartilage Defects.

It is well-established that treating articular cartilage injuries is clinically challenging since they lack blood arteries, nerves, and lymphoid tissue. Recent studies have revealed that bone marrow stem cell-derived exosomes (BMSCs-Exos) exert significant chondroprotective effects through paracrine secretions, and hydrogel-based materials can synergize the exosomes through sustained release. Therefore, this research aims to synthesize an ECM (extracellular matrix)-mimicking gelatin methacryloyl (GelMA) hydrogel modified by gelatin combined with BMSCs-derived exosomes to repair cartilage damage. We first isolated and characterized exosomes from BMSCs supernatant and then loaded the exosomes into GelMA hydrogel to investigate cartilage repair effects in in vitro and in vivo experiments. The outcomes showed that the GelMA hydrogel has good biocompatibility with a 3D (three-dimensional) porous structure, exhibiting good carrier characteristics for exosomes. Furthermore, BMSCs-Exos had a significant effect on promoting chondrocyte ECM production and chondrocyte proliferation, and the GelMA hydrogel could enhance this effect through a sustained-release effect. Similarly, in vivo experiments showed that GelMA-Exos promoted cartilage regeneration in rat joint defects and the synthesis of related cartilage matrix proteins.

Bone mesenchymal stem cell-derived exosome-loaded injectable hydrogel for minimally invasive treatment of spinal cord injury.

Aim: Bone mesenchymal stem cell-derived exosomes (Exos) have been shown to exert therapeutic effects in spinal cord injury (SCI). In this study, we aimed to apply bioengineering approaches to promote Exo retention and their sustained release for SCI repair. Materials & methods: 3D gelatin methacrylate hydrogel (GelMA) was used as a transplanted Exo delivery system (GelMA-Exos). The viability, proliferation, and differentiation of neural stem cells cultured on hydrogel were assessed. Further, GelMA-Exos was injected into the damaged lesions to assess its repair potential. Results: GelMA hydrogel enhanced the retention of Exos, which promoted the neuronal differentiation and extension in vitro. Furthermore, GelMA-Exos promoted neurogenesis and attenuated glial scars in the damaged lesions. Conclusion: The injectable Exo-loaded 3D hydrogel induced neurological functional recovery post SCI.

Statins as potential therapeutic drug for asthma?

BACKGROUND: Statins are lipid-lowering agents that also exhibit pleiotropic effects in decreasing oxidative stress and inflammation. There have been several published studies reporting the use of statins in the treatment of asthma patients, but their results are not consistent. The aim of this study is to determine whether statins are beneficial for asthma administration, and explore the potential covariables that may affect their clinical effectiveness. METHODS: A systematic literature search was performed in PubMed, Embase and Cochrane Center Register of Controlled Trials from inception to September 2012. Randomized controlled trials (RCT), retrospective studies and controlled clinical trials which reported the use of statins in the treatment of asthma patients were eligible. Quality evaluation was conducted for RCT using Jadad criteria. RESULTS: A total of 18 articles were included. In our study, we found no conclusive evidence to demonstrate that statins could enhance the lung function in asthmatics, although, they may reduce airway inflammation. Additionally, the results were not consistent across studies with respect to symptoms, quality of life, maintenance medication, asthma hospitalization/emergency department (ED) visits. CONCLUSIONS: Statins may reduce airway inflammation in asthmatics, without having a significant effect on lung function. Further large sample and multicenter clinical trials are needed to confirm this and to see if there are more responsive phenotypes of asthma.