Ratiometric fluorescence sensing NADH using AIE-dots transducers at the point of care.

Reduced nicotinamide adenine dinucleotide (NADH) has a strong impact on physiological metabolism, and its concentration is related to metabolic and neurodegenerative diseases. A more reliable and accurate detection method for NADH quantitation is needed for early disease diagnosis and point-of-care testing. Aggregation-induced emission (AIE) materials are widely used to improve the sensitivity in analytes assays due to their anti-aggregation-caused quenching property. Here we developed TPA-BQD-Py AIE-dots transducers and evaluated its performance in NADH detection. The NADH concentration-dependent ratiometric sensing was based on electron transfer from TPA-BQD-Py AIE-dots to NADH with variable fluorescence intensity at 584 nm and 470 nm, resulting in high sensitivity (limit of detection at 110 nM), photostability, selectivity, and a rapid and reversible response. We further developed the application of TPA-BQD-Py AIE-dots transducers in in vivo NADH imaging using a smartphone and digital camera, respectively, demonstrating the potential for NADH point-of-care testing.

The Association between Assisted Reproductive Technologies and Neurodevelopmental Disorders in Offspring: An Overview of Current Evidence.

The utilization of assisted reproductive technologies (ART) is on the rise, resulting in a growing population of ART-conceived offspring. The health concerns of this unique population have attracted significant attention. During ART procedures, gametes and early-stage embryos are exposed to various non-physiological conditions, such as manipulation, culture media, and cryopreservation, which may disrupt embryonic development and potentially impact the health of offspring. Notably, the potential impact of ART on neurodevelopment and its association with an increased risk of neurodevelopmental disorders (NDD) later in life remains a subject of debate. This review aims to summarize the current research advancements concerning the effects of ART on neurodevelopment, specifically focusing on the evidence of the relationship between ART, epigenetic modifications, and NDD, including autism spectrum disorder, intellectual disability, attention deficit hyperactivity disorder, and cerebral palsy. Future studies should prioritize large sample sizes, rigorous adjustment for confounding factors, and the use of interdisciplinary approaches to effectively monitor the neurodevelopmental outcomes of ART-conceived children.

Acute Cerebral Ischemia Increases a Set of Brain-Specific miRNAs in Serum Small Extracellular Vesicles.

Small extracellular vesicles (sEVs) miRNAs are promising diagnosis and prognosis biomarkers for ischemic stroke (IS). This study aimed to determine the impact of IS on the serum sEVs miRNA profile of IS patients and a transient middle cerebral artery occlusion (tMCAO) mouse model. Small RNAseq was used to define the serum sEVs miRNA profile in IS patients and healthy controls (HC), and tMCAO mice and sham controls. Among the 1,444 and 1,373 miRNAs identified in human and mouse serum sEVs, the expression of 424 and 37 miRNAs was significantly altered in the IS patients and tMCAO mice, respectively (| Log2FC| ≥ 1, p < 0.01). Notably, five of the top 25 upregulated miRNAs in IS patients were brain-specific or enriched, including hsa-miR-9-3p, hsa-miR-124-3p, hsa-miR-143-3p, hsa-miR-98-5p, and hsa-miR-93-5p. Upregulation of these four miRNAs was further validated by qPCR. Nine of the 20 upregulated miRNAs in tMCAO mice were also brain-specific or enriched miRNAs. Temporal analysis indicated that the dynamics of mmu-miR-9-5p, mmu-miR-124-3p, mmu-miR-129-5p, and mmu-miR-433-3p were closely correlated with the evolution of ischemic brain injury, as their expression increased at 0.5 days after the onset of ischemia, peaked at day 1 or 3, and returned to normal levels at day 7 and 14. Notably, with the exceptions of mmu-miR-128-3p, the expression of the other eight miRNAs in the mouse serum sEVs was unaffected in the lipopolysaccharide (LPS)-induced neuroinflammation model. Together, in this study, we provided a comprehensive view of the influences of IS on the serum sEVs miRNA profile of IS patients and tMCAO mice and demonstrated the increment of a set of brain-specific miRNAs in serum sEVs after acute cerebral ischemia, which could be promising candidates directly reflecting the ischemic brain injury.

Pannexin 1, a large-pore membrane channel, contributes to hypotonicity-induced ATP release in Schwann cells.

Pannexin 1 (Panx 1), as a large-pore membrane channel, is highly permeable to ATP and other signaling molecules. Previous studies have demonstrated the expression of Panx 1 in the nervous system, including astrocytes, microglia, and neurons. However, the distribution and function of Panx 1 in the peripheral nervous system are not clear. Blocking the function of Panx 1 pharmacologically (carbenoxolone and probenecid) or with small interfering RNA targeting pannexins can greatly reduce hypotonicity-induced ATP release. Treatment of Schwann cells with a Ras homolog family member (Rho) GTPase inhibitor and small interfering RNA targeting Rho or cytoskeleton disrupting agents, such as nocodazole or cytochalasin D, revealed that hypotonicity-induced ATP release depended on intracellular RhoA and the cytoskeleton. These findings suggest that Panx 1 participates in ATP release in Schwann cells by regulating RhoA and the cytoskeleton arrangement. This study was approved by the Animal Ethics Committee of Nantong University, China (No. S20180806-002) on August 5, 2018.

Corrigendum: Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury.

[This corrects the article DOI: 10.3389/fncel.2020.00078.].

Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury.

Recovery from spinal cord injury (SCI) remains an unsolved problem. As a major component of the SCI lesion, the glial scar is primarily composed of scar-forming astrocytes and plays a crucial role in spinal cord regeneration. In recent years, it has become increasingly accepted that the glial scar plays a dual role in SCI recovery. However, the underlying mechanisms of this dual role are complex and need further clarification. This dual role also makes it difficult to manipulate the glial scar for therapeutic purposes. Here, we briefly discuss glial scar formation and some representative components associated with scar-forming astrocytes. Then, we analyze the dual role of the glial scar in a dynamic perspective with special attention to scar-forming astrocytes to explore the underlying mechanisms of this dual role. Finally, taking the dual role of the glial scar into account, we provide several pieces of advice on novel therapeutic strategies targeting the glial scar and scar-forming astrocytes.

A monoclonal antibody targeting neuropilin-1 inhibits adhesion of MCF7 breast cancer cells to fibronectin by suppressing the FAK/p130cas signaling pathway.

Neuropilin-1 (NRP-1) is a nontyrosine kinase coreceptor for semaphorin 3A and the vascular endothelial growth factor involved in tumor angiogenesis, growth, and metastasis and is regarded as a promising target for cancer therapy. In the present study, we investigated the effects of an anti-NRP-1 monoclonal antibody (mAb) that we generated for MCF7 breast cancer cellular adhesion studies. MTT, colony formation, and adhesion assays showed that our anti-NRP-1 mAb dose-dependently inhibited MCF7 proliferation and fibronectin adhesion, leading to a rounded cellular morphology. Further, rhodamine phalloidin stain revealed that fibronectin-dependent formation of actin stress fibers was inhibited by anti-NRP-1 mAb. Immunoprecipitation and western blot showed that anti-NRP-1 mAb treatment inhibited the formation of NRP-1-α5ß1 integrin complexes and suppressed the phosphorylation of focal adhesion kinase and p130cas in MCF7 cells. These findings contribute to further understanding the NRP-1 function in cell adhesion and tumor metastasis. Moreover, our anti-NRP-1 mAb is a prospective drug candidate for tumor treatment.

A monoclonal antibody produced against Naked2.

Naked2 (NKD2) is a member of the Naked family and negatively regulates canonical Wnt signaling. NKD2 may play a role in embryo development and tumor formation by affecting Wnt signaling. In the present study, we describe the establishment of a monoclonal antibody against NKD2 (anti-NKD2 MAb) through the hybridoma method. The purified anti-NKD2 MAb measured a titer of 2.56 × 10(5) against NKD2 by indirect ELISA. Western blot analysis, immunoprecipitation, and confocal microscope showed that the anti-NKD2 MAb can specifically combine NKD2 protein in SW480 and LOVO cells. Competitive inhibition assays of Western blot and indirect ELISA showed that the anti-NKD2 MAb can be blocked with NKD2(1-217) protein. The anti-NKD2 MAb would be helpful for further studies on the structure activity relationship, protein detecting, and cell-signaling pathway of NKD2.