Biomedical Journal最新文献

Extracellular vesicles (EVs) are enclosed by a phospholipid bilayer and can be secreted by most types of cells. EVs deliver cargo from the secreting cell into the cytoplasm of recipient cells, influencing the function of the recipient cells. EVs are attracting increasing attention from a broad range of clinicians and scientists due to their ability to promote or inhibit various physiological pathways or pathological conditions. This special issue of Biomedical Journal contains articles describing the biogenesis and biodistribution of EVs and their role in the intercellular transfer of various molecules or viruses to target cells, in rejecting allogeneic transplants and maintaining immune tolerance of the allogeneic fetus, and in modulating innate and adaptive immunity. Characterization of the role of EVs in various pathological conditions and our ability to engineer modified EVs may lead to discovery of novel biomarkers and development of therapeutic strategies for treatment of disease.

Two key problems of allo-tolerance during fetal-maternal co-existence are: 1) it's focus must be local, allowing the mother's continued peripheral immune competence to resist pathogens ubiquitously, and 2) it must propagate itself, i.e. continuously recruit new re-enforcements of the local tolerant state. Both are solved by the exosomal pathway of Tregs & Bregs. While the fetal-maternal accomodations of pregnancy terminate at the time of partrurition, geography, climate and the endemic pathogens of the environment surrounding the mother-baby pair would then define the short and long-term effects of their immunologic interaction.

This issue of the Biomedical Journal highlights major advancements in drug delivery, including aptamer-functionalized liposomes and nanozymes. A new biomarker combination shows promise for improved diagnosis of idiopathic pulmonary fibrosis. Mesenchymal stem cells are suggested to mitigate inflammation in systemic lupus erythematosus, and a potential positive feedback loop driven by a prevalent mRNA modification is suggested to enhance NSCLC progression. Additional articles explore a pathological impact on autophagy leading to muscle dysfunction, the benefits of integrating an orphan drug with standard therapy for glioblastoma patients, and the influence of transcriptional super-enhancers in early-stage esophageal squamous cell carcinoma. Finally, this issue provides insights into the roles of different Blastocystis subtypes, and the use of laser light for treating infantile hemangioma.

Background

Infantile hemangioma (IH) is a common vascular tumor in female infants, which can lead to aesthetic issues and facial scarring. This study aimed to investigate the inhibitory effects and underlying mechanisms of 755 nm long-pulsed alexandrite laser on IH.

Methods

Hemangioma endothelial cells (HemECs) were exposed to 755 nm long-pulsed alexandrite laser to evaluate its impact on cell proliferation and apoptosis. A patient-derived xenograft model was established to assess the inhibitory effects of laser treatment on IH in vivo.

Results

In vitro, 755 nm long-pulsed alexandrite laser effectively suppressed the proliferation of HemECs and induced cell apoptosis. Laser treatment significantly inhibited the volume and weight of tumors, accompanied by significant downregulation of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) expression levels in both hemangioma cells and tumors. Additionally, laser treatment resulted in the conversion of VEGFA_165a to VEGFA_165b. TUNEL staining demonstrated increased apoptosis in tumor cells after laser treatment, along with upregulation of cleaved caspase-3 and Bax, and downregulation of Bcl-2.

Conclusion

In addition to the principle of selective photothermal decomposition, modulation of the VEGF/PI3K/Akt axis may serve as a potential mechanism for IH treatment using a long pulse-width 755 nm laser. This sheds valuable light on the molecular mechanisms underlying IH pathogenesis and potential therapeutic targets while providing a theoretical basis for the safe and efficient management of proliferative IH using laser therapy.

Background

Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by a CTG repeat expansion in the 3′ untranslated region of the DM1 protein kinase gene. Characteristic degenerative muscle symptoms include myotonia, atrophy, and weakness. We previously proposed an Musashi homolog 2 (MSI2)>miR-7>autophagy axis whereby MSI2 overexpression repressed miR-7 biogenesis that subsequently de-repressed muscle catabolism through excessive autophagy. Because the DM1 HSA^LR mouse model expressing expanded CUG repeats shows weak muscle-wasting phenotypes, we hypothesized that MSI2 overexpression was sufficient to promote muscle dysfunction in vivo.

Methods

By means of recombinant AAV murine MSI2 was overexpressed in neonates HSA^LR mice skeletal muscle to induce DM1-like phenotypes.

Results

Sustained overexpression of the murine MSI2 protein in HSA^LR neonates induced autophagic flux and expression of critical autophagy proteins, increased central nuclei and reduced myofibers area, and weakened muscle strength. Importantly, these changes were independent of MBNL1, MBNL2, and Celf1 protein levels, which remained unchanged upon Msi2 overexpression.

Conclusions

Globally, molecular, histological, and functional data from these experiments in the HSA^LR mouse model confirms the pathological role of MSI2 expression levels as an atrophy-associated component that impacts the characteristic muscle dysfunction symptoms in DM1 patients.

Among the various targeting ligands for drug delivery, aptamers have attracted much interest in recent years because of their smaller size compared to antibodies, ease of modification, and better batch-to-batch consistency. In addition, aptamers can be selected to target both known and even unknown cell surface biomarkers. For drug loading, liposomes are the most successful vehicle and many FDA-approved formulations are based on liposomes. In this paper, aptamer-functionalized liposomes for targeted drug delivery are reviewed. We begin with the description of related aptamers selection, followed by methods to conjugate aptamers to liposomes and the fate of such conjugates in vivo. Then a few examples of applications are reviewed. In addition to intravenous injection for systemic delivery and hoping to achieve accumulation at target sites, for certain applications, it is also possible to have aptamer/liposome conjugates applied directly at the target tissue such as intratumor injection and dropping on the surface of the eye by adhering to the cornea. While previous reviews have focused on cancer therapy, the current review mainly covers other applications in the last four years. Finally, this article discusses potential issues of aptamer targeting and some future research opportunities.