Corrigendum: Transcription factor SS18L1 regulates the proliferation, migration and differentiation of Schwann cells in peripheral nerve injury.

[This corrects the article DOI: 10.3389/fvets.2022.936620.].

Skin precursor-derived Schwann cells accelerate in vivo prevascularization of tissue-engineered nerves to promote peripheral nerve regeneration.

Prevascularization strategies have become a hot spot in tissue engineering. As one of the potential candidates for seed cells, skin precursor-derived Schwann cells (SKP-SCs) were endowed with a new role to more efficiently construct prevascularized tissue-engineered peripheral nerves. The silk fibroin scaffolds seeded with SKP-SCs were prevascularized through subcutaneously implantation, which was further assembled with the SKP-SC-containing chitosan conduit. SKP-SCs expressed pro-angiogenic factors in vitro and in vivo. SKP-SCs significantly accelerated the satisfied prevascularization in vivo of silk fibroin scaffolds compared with VEGF. Moreover, the NGF expression revealed that pregenerated blood vessels adapted to the nerve regeneration microenvironment through reeducation. The short-term nerve regeneration of SKP-SCs-prevascularization was obviously superior to that of non-prevascularization. At 12 weeks postinjury, both SKP-SCs-prevascularization and VEGF-prevascularization significantly improved nerve regeneration with a comparable degree. Our figures provide a new enlightenment for the optimization of prevascularization strategies and how to further utilize tissue engineering for better repair.

miR-328a-3p modulates the proliferative and migratory abilities of Schwann cells in peripheral nerves.

MicroRNAs (miRNAs) modulate Schwann cell phenotype. Here miR-328a-3p amounts after peripheral nerve damage were determined in injury stumps of the sciatic nerve in rats administered surgical crush. Quantitative real-time reverse transcription-polymerase chain reaction was performed to assess miR-328a-3p levels 0, 1, 4, 7 and 14 days post-sciatic nerve damage. The results showed miR-328a-3p was upregulated after nerve damage. CCK8 and EdU assays revealed elevated miR-328a-3p amounts suppressed Schwann cell viability and proliferation, respectively. Next, the migratory potential of cells was assessed by the Transwell chamber and wound healing assays. We found elevated miR-328a-3p amounts also suppressed Schwann cell migration. Conversely, low miR-328a-3p amounts promoted Schwann cell migration. The possible miR-328a-3p targets were predicted by bioinformatics. The 15 target genes retrieved provided insights into miR-328a-3p's effects on Schwann cells and expanded the understanding of miR-328a-3p's biological functions in the peripheral nervous system. Collectively, these findings revealed miR-328a-3p's effects on Schwann cells and provided further insights into the functions of miRNAs in peripheral nerves.

Blood vessel remodeling in late stage of vascular network reconstruction is essential for peripheral nerve regeneration.

One of the bottlenecks of advanced study on tissue engineering in regenerative medicine is rapid and functional vascularization. For a deeper comprehension of vascularization, the exhaustive, dynamic, and three-dimensional depiction of perfused vascular network reconstruction during peripheral nerve regeneration was performed using Micro-CT scanning. The 10 mm defect of sciatic nerve in rat was bridged by the autologous or tissue engineered nerve. The blood vessel anastomosis between nerve stumps and autologous nerve accomplished at 4 days to 1 week after surgery, which was a sufficient basis for the mature vascular network re-establishment. The stronger ability for sprouting angiogenesis and vascular remodeling of autologous nerve compared with tissue engineered nerve was revealed. However, common phases of vascularization in peripheral nerve regeneration were painted: hypoxic initiation, sprouting angiogenesis, and remodeling and maturation. The effect of less-concerned vascular remodeling on nerve regeneration was further analyzed after nerve crush injury. The blockage of vascular remodeling in late stage by VEGF injection significantly inhibited axons and myelin sheaths regeneration, which attenuated the impulse conduction toward reinnervated muscles. It was illustrated that a large amount of immature blood vessels rather than necessary vascular remodeling elevated local inflammation level in nerve regeneration microenvironment. The figures inspired us to understand the close connections between vascularization and peripheral nerve regeneration from a broader dimension to achieve better constructions, regulations and repair effects of tissue engineered nerves in clinic.

Transcription factor SS18L1 regulates the proliferation, migration and differentiation of Schwann cells in peripheral nerve injury.

Transcription factors bind to specific DNA sequences, modulate the transcription of target genes, and regulate various biological processes, including peripheral nerve regeneration. Our previous analysis showed that SS18L1, a gene encoding the transcription factor SS18-like protein 1, was differentially expressed in the distal sciatic nerve stumps after rat sciatic nerve transection injury, but its effect on peripheral nerve injury has not been reported. In the current study, we isolated and cultured primary Schwann cells, and examined the role of SS18L1 for the biological functions of the cells. Depletion of SS18L1 by siRNA in Schwann cells enhanced cell proliferation and inhibited cell migration, as determined by EdU assay and transwell migration assay, respectively. In addition, silencing of SS18L1 inhibited Schwann cell differentiation induced by HRG and cAMP. Bioinformatics analyses revealed an interaction network of SS18L1, including DF2, SMARCD1, SMARCA4, and SMARCE1, which may be implicated in the regulatory functions of SS18L1 on the proliferation, migration and differentiation of Schwann cells. In conclusion, our results revealed a temporal expression profile of SS18L1 in peripheral nerve injury and its potential roles during the process of nerve recovery.

miR-140-3p suppresses the proliferation and migration of macrophages.

Macrophages benefit myelin debris removal, blood vessel formation, and Schwann cell activation following peripheral nerve injury. Identifying factors that modulate macrophage phenotype may advantage the repair and regeneration of injured peripheral nerves. microRNAs (miRNAs) are important regulators of many physiological and pathological processes, including peripheral nerve regeneration. Herein, we investigated the regulatory roles of miR-140-3p, a miRNA that was differentially expressed in injured rat sciatic nerves, in macrophage RAW264.7 cells. Observations from EdU proliferation assay demonstrated that elevated miR-140-3p decreased the proliferation rates of RAW264.7 cells while suppressed miR-140-3p increased the proliferation rates of RAW264.7 cells. Transwell-based migration assay showed that up-regulated and down-regulated miR-140-3p led to elevated and reduced migration abilities, respectively. However, the abundances of numerous phenotypic markers of M1 and M2 macrophages were not significantly altered by miR-140-3p mimic or inhibitor transfection. Bioinformatic analysis and miR-140-3p-induced gene suppression examination suggested that Smad3 might be the target gene of miR-140-3p. These findings illuminate the inhibitory effects of miR-140-3p on the proliferation and migration of macrophages and contribute to the cognition of the essential roles of miRNAs during peripheral nerve regeneration.

Elevated matrix metalloproteinase 9 supports peripheral nerve regeneration via promoting Schwann cell migration.

Matrix metalloproteinases (MMPs) are important contributing factors of tissue remodeling and wound healing. MMP9, a predominant soluble MMP, has been discovered as one of the most up-regulated genes in peripheral nerves after nerve injury, implying the potential regulatory roles of MMP9 during peripheral nerve regeneration. Considering that Schwann cell is a main cell population in peripheral nerves and MMP9 is secreted by Schwann cells, here, we investigated the biological functions of MMP9 on Schwann cell phenotype modulation. MMP9 gene knockdown or MMP9 recombinant protein exposure significantly hinders or elevates the migration ability of cultured Schwann cells, respectively. Direct application of MMP9 recombinant protein to sciatic nerve injured rats promotes Schwann cell migration, blood vessel formation, axon elongation, and myelin wrapping. Genetic exploration of MMP9-induced changes indicates that MMP9 regulates the extracellular region as well as the intracellular metabolism of Schwann cells. Our present study illuminates the importance of elevated MMP9 after nerve injury from the functional aspect and enhances our comprehension of the mechanisms underlying peripheral nerve regeneration.

RHPN2 Promotes Malignant Cell Behaviours in Ovarian Cancer by Activating STAT3 Signalling.

BACKGROUND: Ovarian cancer is the fifth most common cause of cancer-related deaths and accounts for 3% of cancer cases occurring in women. Therefore, determining the underlying genes that can promote ovarian cancer progression is of great urgency. It has been reported that RHPN2 promotes tumour progression in various types of cancer, but its role in ovarian cancer pathogenesis remains unknown. MATERIALS AND METHODS: In this study, bioinformatic datasets were used to predict the expression of RHPN2 in clinical samples and determine the relationship between RHPN2 and the prognosis of ovarian cancer patients. Clinical samples were used to verify the prediction. RHPN2-targeting shRNA was used to investigate the effect of RHPN2 on ovarian cancer cells, and following RHPN2 knockdown, the proliferative and migratory capacities of ovarian cancer cells were tested. To determine the downstream signalling target of RHPN2, a luciferase reporter assay was conducted, and an animal experiment was carried out to confirm the effect of RHPN2 in vivo. RESULTS: The public datasets indicated that ovarian cancer tissues showed significantly higher RHPN2 expression than para-cancer normal tissues, and poor prognosis was observed in patients with higher RHPN2 expression, which was further confirmed in clinical samples. After RHPN2 was knocked down, the proliferation and migration of ovarian cancer cells were significantly impaired; a luciferase reporter assay indicated that the STAT3 signalling pathway was the most highly affected, and RHPN2 downregulation inhibited STAT3 nuclear translocation. STAT3 inhibitors partially rescued the tumour-promoting effect induced by RHPN2 overexpression, which was further confirmed by animal experiments. CONCLUSION: Collectively, our results indicate that RHPN2 promotes malignant behaviours in ovarian cancer by activating STAT3 signalling.

Complete Mitogenomic Structure and Phylogenetic Implications of the Genus Ostrinia (Lepidoptera: Crambidae).

To understand mitogenome characteristics and reveal phylogenetic relationships of the genus Ostrinia, including several notorious pests of great importance for crops, we sequenced the complete mitogenomes of four species: Ostrinia furnacalis (Guenée, 1854), Ostrinia nubilalis (Hübner, 1796), Ostrinia scapulalis (Walker, 1859) and Ostrinia zealis (Guenée, 1854). Results indicate that the four mitogenomes-O. furnacalis, O. nubilalis, O. scapulalis, and O. zealis-are 15,245, 15,248, 15,311, and 15,208 bp in size, respectively. All four mitogenomes are comprised of 37 encoded genes and a control region. All 13 protein-coding genes (PCGs) initiate with ATN and terminate with TAN, with the exception of cox1 that starts with CGA, and cox1, cox2, and nad5 that terminate with an incomplete codon T. All transfer RNA genes (tRNAs) present the typical clover-leaf secondary structure except for the trnS1 (AGN) gene. There are some conserved structural elements in the control region. Our analyses indicate that nad6 and atp6 exhibit higher evolution rates compared to other PCGs. Phylogenetic analyses based on mitogenomes using both maximum likelihood (ML) and Bayesian inference (BI) methods revealed the relationship (O. palustralis + (O. penitalis + (O. zealis + (O. furnacalis + (O. nubilalis + O. scapulalis))))) within Ostrinia.

Clinical efficacy and safety of nicergoline combined with oxiracetam in the treatment of vascular cognitive impairment.

As a α1-adrenergic receptor antagonist, nicergoline can induce vasodilation and increase arterial blood flow. Its clinical application can effectively prevent and treat cognitive impairment and reduce cognitive decline and comprehensively improve patients' daily living ability and social function. The clinical efficacy of nicergoline combined with oxiracetam in the treatment of vascular cognitive impairment after stroke was analyzed. 120 patients with cognitive impairment after stroke were randomly divided into nicergoline group and Experience group. They were treated with nicergoline and nicergoline combined with oxiracetam respectively. Both groups were treated for one month. Montreal Cognitive Assessment Scale (MoCA) was used to evaluate the cognitive function of the two groups before and after treatment, and the clinical efficacy was compared. The results showed that the average score of MoCA in the combined group was (5.97±2.06), higher than that in the nicergoline group (3.53±1.44). The change of MoCA score was the most significant. There was significant difference between the nicergoline group and the combined group (t=4.21, P<0.01). The combined group had the highest effective rate and the total effective rate was 93.3%. Conclusion: Nicergoline and oxiracetam are effective drugs in the treatment of vascular cognitive impairment (VCI). The combined use of nicergoline and oxiracetam is better than that of nicergoline alone. The combined use of nicergoline and oxiracetam can significantly improve the severity of symptoms and quality of life in patients with vascular cognitive impairment after stroke. The clinical effect is definite.

Delineating closely related species of Tylostega Meyrick (Lepidoptera: Crambidae: Spilomelinae) from mainland China using DNA barcodes.

Integrative taxonomic study of three species of the genus Tylostega revealed that the genetic distances of the COI gene among the tested species was relatively large (3.27-7.60%). The Automatic Barcode Gap Discovery (ABGD) system performed better than the Barcode Index Number (BIN) in discriminating closely related species. This work provides a molecular baseline for future integrative taxonomic study of Crambidae.

A new cryptic species of Nagiella Munroe from China revealed by DNA barcodes and morphological evidence (Lepidoptera, Crambidae, Spilomelinae).

Nagiella occultalis Misbah & Yang, sp. n. from China is described and illustrated. This new species is very similar to N. quadrimaculalis (Kollar, 1844) in general morphological characters of forewing and male genitalia. Molecular evidence shows that these two species diverge in COI barcode region by more than 3.2%. Sequence divergence among the two species is congruent with subtle morphological differences. Wing venation and male genitalia of the two species are compared and illustrated.