Neural tissue-engineered prevascularization in vivo enhances peripheral neuroregeneration via rapid vascular inosculation.

Neural tissue engineering techniques typically face a significant challenge, simulating complex natural vascular systems that hinder the clinical application of tissue-engineered nerve grafts (TENGs). Here, we report a subcutaneously pre-vascularized TENG consisting of a vascular endothelial growth factor-induced host vascular network, chitosan nerve conduit, and inserted silk fibroin fibers. Contrast agent perfusion, tissue clearing, microCT scan, and blood vessel 3D reconstruction were carried out continuously to prove whether the regenerated blood vessels were functional. Moreover, histological and electrophysiological evaluations were also applied to investigate the efficacy of repairing peripheral nerve defects with pre-vascularized TENG. Rapid vascular inosculation of TENG pre-vascularized blood vessels with the host vascular system was observed at 4 â€‹d bridging the 10 â€‹mm sciatic nerve defect in rats. Transplantation of pre-vascularized TENG in vivo suppressed proliferation of vascular endothelial cells (VECs) while promoting their migration within 14 â€‹d post bridging surgery. More importantly, the early vascularization of TENG drives axonal regrowth by facilitating bidirectional migration of Schwann cells (SCs) and the bands of Büngner formation. This pre-vascularized TENG increased remyelination, promoted recovery of electrophysiological function, and prevented atrophy of the target muscles when observed 12 weeks post neural transplantation. The neural tissue-engineered pre-vascularization technique provides a potential approach to discover an individualized TENG and explore the innovative neural regenerative process.

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.

[Advancements in virtual screening techniques for study of enzyme inhibitor compounds].

Enzymes are closely associated with the onset and progression of numerous diseases, making enzymes a primary target in innovative drug development. However, the challenge remains in identifying compounds that exhibit potent inhibitory effects on the target enzymes. With the continuous expansion of the total number of natural products and increasing difficulty in isolating and enriching new compounds, traditional high-throughput screening methods are finding it increasingly challenging to meet the demands of new drug development. Virtual screening, characterized by its high efficiency and low cost, has gradually become an indispensable technology in drug development. It represents a prominent example of the integration of artificial intelligence with biopharmaceuticals and is an inevitable trend in the rapid development of innovative drug screening in the future. Therefore, this article primarily focused on systematically reviewing the recent applications of virtual screening technology in the development of enzyme inhibitors and explored the prospects and advantages of using this technology in developing new drugs, aiming to provide essential theoretical insights and references for the application of related technologies in the field of new drug development.

Feasibility of transbronchial lung cryobiopsy in patients with veno-venous extracorporeal membrane oxygenation support.

Background: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is essential life support in patients with severe acute hypoxaemic respiratory failure. However, biopsies should be considered for some patients with unknown aetiology. This study aims to evaluate the feasibility of transbronchial lung cryobiopsy (TBLC) in such patients. Methods: All patients with acute hypoxaemic respiratory failure of unknown aetiology who underwent TBLC with VV-ECMO support were retrospectively reviewed. Patients' characteristics, ventilation settings, procedure parameters, complications, pathological diagnosis and survival were summarised and analysed. Results: Eight female and five male patients with VV-ECMO support underwent TBLC. The median age was 58 (interquartile range (IQR) 38-67) years old. Concurrent diseases were present in 10 of the 13 patients, seven of which were immunosuppressed. The median time between biopsy and VV-ECMO establishment was 2.0 (IQR 0.5-6.5) days. No patient died from the procedure. Neither pneumothorax nor severe bleeding occurred in any of the patients. Five of the 13 patients experienced moderate bleeding, and all bleeding events were successfully controlled with prophylactic balloon blockers. Pathological diagnosis by TBLC was obtained in all patients, and the diagnosis of diffuse alveolar damage was made in nine of them. Conclusions: In patients with VV-ECMO support, the TBLC procedure is generally safe when standardised bleeding prophylaxis is in place. TBLC contributes to identifying underlying aetiologies in patients with acute hypoxaemic respiratory failure of unknown aetiology.

Effects and molecular mechanisms of Achyranthes bidentata polypeptide k on proliferation of Schwann cells.

BACKGROUND: Achyranthes bidentata polypeptide k (ABPPk) is an active ingredient separated from the Achyranthes bidentata polypeptides (ABPP) in traditional Chinese medicine. In the present study, we investigated the promoting effects and molecular mechanisms of ABPPk on the proliferation of Schwann cells (SCs). METHODS: Primary SCs were cultured with ABPPk or nerve growth factor (NGF) in vitro, and cell viability, cell cycle, EdU assay, and the expressions of proliferating cell nuclear antigen (PCNA) and Ki67 were analyzed. In addition, RNA-seq was used for bioinformatics analysis at different time points. PCNA was detected at different time points in a rat sciatic nerve injury model to further determining the role of ABPPk in sciatic nerve injury repair. RESULTS: We found that ABPPk could effectively promote the proliferation of SCs, while ABPPk and NGF had different molecular mechanisms for their proliferation at different time points. Weighted gene co-expression network analysis (WGCNA) showed that ABPPk was mainly involved in the positive regulation of cell proliferation and epigenetic regulation of cell proliferation, while the main cell proliferation-related modules that NGF participated in were attenuation of negative regulation of cell proliferation and positive regulation of cell cycle. There were significant differences in the genes involved in different modules between the two groups, and ABPPk differed from NGF in the biological process of SC migration, differentiation, movement, and development in terms of action time and key genes. Functional enrichment analysis revealed ABPPk had more advantages and participation in the axon extension and vascular system areas. Furthermore, ABPPk significantly promoted the proliferation of SCs in vivo. CONCLUSIONS: Through in vitro and in vivo studies, we identified the promoting effects of ABPPk on the proliferation of SCs. Using high-throughput sequencing technology, our work more comprehensively revealed the characteristics and mechanism of ABPPk on SCs. These results further enrich an understanding of the positive function and molecular mechanism of ABPPk in peripheral nerve regeneration and are conducive to the discovery of new therapeutic targets for peripheral nerve regeneration.

The balanced microenvironment regulated by the degradants of appropriate PLGA scaffolds and chitosan conduit promotes peripheral nerve regeneration.

Tissue-engineered nerve grafts (TENGs) are the most promising way for repairing long-distance peripheral nerve defects. Chitosan and poly (lactic-co-glycolic acid) (PLGA) scaffolds are considered as the promising materials in the pharmaceutical and biomedical fields especially in the field of tissue engineering. To further clarify the effects of a chitosan conduit inserted with various quantity of poly (lactic-co-glycolic acid) (PLGA) scaffolds, and their degrades on the peripheral nerve regeneration, the chitosan nerve conduit inserted with different amounts of PLGA scaffolds were used to repair rat sciatic nerve defects. The peripheral nerve regeneration at the different time points was dynamically and comprehensively evaluated. Moreover, the influence of different amounts of PLGA scaffolds on the regeneration microenvironment including inflammatory response and cell state were also revealed. The modest abundance of PLGA is more instrumental to the success of nerve regeneration, which is demonstrated in terms of the structure of the regenerated nerve, reinnervation of the target muscle, nerve impulse conduction, and overall function. The PLGA scaffolds aid the migration and maturation of Schwann cells. Furthermore, the PLGA and chitosan degradation products in a correct ratio neutralize, reducing the inflammatory response and enhancing the regeneration microenvironment. The balanced microenvironment regulated by the degradants of appropriate PLGA scaffolds and chitosan conduit promotes peripheral nerve regeneration. The findings represent a further step towards programming TENGs construction, applying polyester materials in regenerative medicine, and understanding the neural regeneration microenvironment.

A rearrangement of saccharin-derived cyclic ketimines with 3-chlorooxindoles leading to spiro-1,3-benzothiazine oxindoles.

An unusual rearrangement of saccharin-derived cyclic ketimines (SDCIs) and 3-chlorooxindoles has been developed to provide a series of spiro-1,3-benzothiazine oxindoles. The reaction features simple manipulations, short reaction times, mild reaction conditions and inexpensive reagents. It is the first example where SDCIs serve as a ring-opening reagent in organic synthesis.

The Effect of Coronary Angiography Timing on Cardiac Surgery Associated Acute Kidney Injury Incidence and Prognosis.

Introduction: Acute kidney injury has been identified as a common complication of cardiac surgery. To date, the effect of the time interval from coronary angiography to cardiac surgery on postoperative acute kidney injury is still controversial. The aim of this study was to investigate the relationship between the timing of coronary angiography and cardiac surgery associated acute kidney injury. Methods: Eight hundred thirteen patients who underwent coronary angiography and cardiac surgery successively from January 2017 to December 2018 were included in this retrospective cohort study. We applied multivariate logistic regression, propensity score analysis, and subgroup analysis to evaluate the association between the time interval and postoperative acute kidney injury incidence and prognosis. Meta-analysis was conducted to verify the results. Results: The overall incidence of the cardiac surgery associated acute kidney injury was 28.8%. Age (OR = 1.046, 95%CI: 1.017-1.075), cardiopulmonary bypass (OR = 3.439, 95%CI: 1.316-8.986) and diabetes (OR = 2.522, 95%CI: 1.439-4.417) were found to be independent risk factors of postoperative acute kidney injury in multivariate logistic regression and propensity score analysis. Undergoing cardiac surgery within 7 days after coronary angiography was not associated with increased incidence of postoperative acute kidney injury or worse prognosis. Meta-analysis obtained consistent results. Conclusions: The time interval shorter than 7 days had no influence on cardiac surgery associated acute kidney injury incidence and prognosis. The decision of delaying the surgery should be made after comprehensive evaluation of the patient.

Protective effects and molecular mechanisms of Achyranthes bidentata polypeptide k on Schwann cells.

BACKGROUND: Achyranthes bidentata polypeptide k (ABPPk) is an active ingredient used in traditional Chinese medicine separated from Achyranthes bidentata polypeptides. So far, the role of ABPPk in peripheral nerve protection has not been comprehensively studied. METHODS: In this study, primary Schwann cells exposed to serum deprivation were treated with ABPPk or nerve growth factor (NGF) in vitro. Cell viability, cell apoptosis, apoptosis-related protein expression, and antioxidant enzyme activity were analyzed. To further explore the underlying molecular mechanisms and key regulatory molecules involved in the effects of ABPPk, integrative and dynamic bioinformatics analysis at different time points was carried out following RNA-seq of Schwann cells subjected to serum deprivation. RESULTS: We found that ABPPk could effectively reduce Schwann cell apoptosis caused by serum deprivation, which was comparable to NGF's anti-apoptotic effects. ABPPk had the largest number of upregulated and downregulated differential expression genes at the earliest 0.5 h time, while NGF had fewer differential expression genes at this early stage. The significant difference at this time point between the two groups was also displayed in heatmaps. The molecular regulation of diseases and functions and canonical pathways revealed that ABPPk had more participation and advantages in the vasculature and immune system areas, especially angiogenesis regulation. Also, ABPPk demonstrated an earlier start in these molecular regulations than NGF. Furthermore, the analysis of transcription factors also illustrated that ABPPk not only had more key initial regulatory factors participating in vascular-related processes, but these also remained for a longer period. There was no significant difference in neural-related molecular regulation between the two groups. CONCLUSIONS: Using high-throughput sequencing technology, our work unveiled the protective effects of ABPPk on Schwann cells after serum deprivation in a more comprehensive manner. These results further enrich the positive functions and molecular mechanisms of ABPPk and traditional Chinese medicine and benefit the discovery of novel therapeutic targets for peripheral nerve regeneration.

Effects of Salvia miltiorrhiza injection on apoptosis of Schwann cells induced by hydrogen peroxide.

BACKGROUND: Salvia miltiorrhiza is a traditional Chinese medicine with remarkable antioxidant, antibacterial, and anticoagulant properties. In the present study, we investigated the effects of Salvia miltiorrhiza injection in protecting Schwann cells (SCs) from hydrogen peroxide (H2O2)-induced cell apoptosis. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and immunofluorescence staining were used to detect the establishment of the SC apoptosis model induced by H2O2. The effect of Salvia miltiorrhiza injection on injured cell morphology was observed, and the effect on cell apoptosis was determined by Annexin V-fluorescein isothiocyanate (FITC) apoptosis detection kit and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Western blotting analysis was used to detect the effect of Salvia miltiorrhiza injection on apoptosis-related protein expression. RESULTS: The results of the MTT assay showed that cell activity significantly decreased after treatment with 1 mM H2O2, but different concentrations of Salvia miltiorrhiza injection could improve cell activity at different degrees. The number of cells increased significantly after treatment with Salvia miltiorrhiza injection. Annexin V-FITC/PI double staining and TUNEL results revealed that Salvia miltiorrhiza injection could significantly reduce apoptosis induced by H2O2. Western blotting analysis showed that the expression of Bcl-2 was significantly upregulated, while the expression level of Bax was significantly downregulated. CONCLUSIONS: Salvia miltiorrhiza injection can protect SCs from H2O2-induced cell apoptosis, and has potential therapeutic effects in neurological disease.

The Association Between Obesity and Risk of Acute Kidney Injury After Cardiac Surgery.

Objective: To determine the relationship between obesity and the risk of AKI after cardiac surgery (CS-AKI) in a cohort study. Methods: A total of 1,601 patients undergoing cardiac surgery were collected and their incidence of CS-AKI was recorded. They were divided into underweight, normal weight, overweight, and obese groups. Logistic regression was used to estimate the association between BMI (body mass index) and CS-AKI risk. Then, a meta-analysis of published cohort studies was conducted to confirm this result using PubMed and Embase databases. Results: A significant association was observed in this independent cohort after adjusting age, gender, hypertension and New York Heart Association classification (NYHA) class. Compared with normal BMI group (18.5 ≤ BMI < 24.0), the individuals with aberrant BMI level had an increased AKI risk (OR: 1.68, 95% CI: 1.01-2.78) for BMI < 18.5 group and (OR: 1.43, 95% CI: 0.96-2.15) for BMI ≥ 28.0. Interestingly, the U-shape curve showed the CS-AKI risk reduced with the increasing of BMI when BMI ≤ 24.0. As BMI increases with BMI > 24.0, the risk of developing CS-AKI increased significantly. In the confirmed meta-analysis, compared with normal weight, overweight group with cardiac surgery had higher AKI risk (OR: 1.28, 95% CI: 1.16-1.41, Pheterogeneity = 0.49). The similar association was found in obesity subgroup (OR: 1.79, 95% CI: 1.57-2.03, Pheterogeneity = 0.42). Conclusion: In conclusion, the results suggested that abnormal BMI was a risk factor for CS-AKI independently.

The oncogenic roles of 27-hydroxycholesterol in glioblastoma.

Glioblastoma is the most frequent primary malignant brain tumor in adults. Oxysterols are oxidation products of cholesterol generated by enzymatic reactions. 27-hydroxycholesterol (27-HC), an oxysterol, is an abundant metabolite of cholesterol. 27-HC significantly accelerates mammary cancer growth, proliferation and progression in experimental models. However, to the best of our knowledge, the effect of 27-HC on glioblastoma has not been studied. Therefore, the present study aimed to determine the exact role of 27-HC in glioblastoma. The present study demonstrated that 27-HC promoted proliferation, epithelial to mesenchymal transition, colony formation, migration and invasion of U251 and U118 MG glioblastoma cells. Treatment with 27-HC was also associated with an increase in the formation of glioblastoma-initiating cells in U251 and U118 MG cell lines. Additionally, it was observed that high levels of 27-HC in glioblastoma tissues were associated with poor outcome in patients. In conclusion, 27-HC, a primary metabolite of cholesterol, may serve an important role in the progression of glioblastoma.

Achyranthes bidentata Polypeptide Protects Schwann Cells From Apoptosis in Hydrogen Peroxide-Induced Oxidative Stress.

ABPPk, the active ingredient separated from Achyranthes bidentata polypeptides, is a traditional Chinese medicine with multiple pharmaceutical properties. In this study, we investigated the molecular mechanisms of ABPPk in protecting Schwann cells (SCs) from H2O2-induced cell apoptosis. The viability of SCs pretreated with ABPPk was elevated significantly by MTT assay estimation. Meanwhile, the apoptosis of SCs was reduced which was showed in flow cytometry and transferase-mediated dUTP nick end labeling analysis. Furthermore, the addition of ABPPk also increased the activities of SOD and GSH accompanied with a decrease in MDA and LDH activities. According to Western blot analysis, the upregulation of Bcl-2, also downregulation of Bax and cleaved caspase-3 were demonstrated in SCs which was ABPPk pretreated. Further research showed that PI3K/AKT and ERK1/2 pathways in SCs have been activated after pretreatment of ABPPk. Collectively, results in our study suggested that ABPPk protected SCs from H2O2-induced oxidative damage by reducing the expression of apoptotic molecules and enhancing the activities of antioxidant enzymes, which inhibited the apoptosis of SCs modulated by PI3K/AKT and ERK1/2 signaling pathways. In our perspectives, ABPPk as an active factor with its antioxidative activities has potential and promising therapeutic effects in the prevention of neurologic disorders.

Effect of Spp1 on nerve degeneration and regeneration after rat sciatic nerve injury.

BACKGROUND: Wallerian degeneration (WD) in injured peripheral nerves is associated with a large number of up- or down-regulated genes, but the effects of these changes are poorly understood. In our previous studies, we reported some key factors that are differentially expressed to activate nerve degeneration and regeneration during WD. Here, we determined the effects of secreted phosphoprotein 1 (Spp1) on WD after rat sciatic nerve injury. RESULTS: Spp1 was upregulated from 6 h to 14 days after sciatic nerve injury. Altered expression of Spp1 in Schwann cells (SC) resulted in altered mRNA and protein expression levels for cytokines, c-Fos, PKCα and phospho-ERK/ERK and affected SC apoptosis in vitro. Silencing of Spp1 expression in SCs using siRNA technology reduced proliferation and promoted migration of SCs in vitro. By contrast, overexpression of Spp1 promoted proliferation and reduced migration in SCs in vitro. Differential expression of Spp1 after sciatic nerve injury in vivo altered the expression of cytokines, c-Fos, PKCα, and the p-ERK/ERK pathway. CONCLUSIONS: Spp1 is a key regulatory factor that affects nerve degeneration and regeneration through c-Fos, PKCα and p-ERK/ERK pathways after rat sciatic nerve injury. These results shed new light on the role of Spp1 in nerve degeneration and regeneration during WD.

Gekko japonicus genome reveals evolution of adhesive toe pads and tail regeneration.

Reptiles are the most morphologically and physiologically diverse tetrapods, and have undergone 300 million years of adaptive evolution. Within the reptilian tetrapods, geckos possess several interesting features, including the ability to regenerate autotomized tails and to climb on smooth surfaces. Here we sequence the genome of Gekko japonicus (Schlegel's Japanese Gecko) and investigate genetic elements related to its physiology. We obtain a draft G. japonicus genome sequence of 2.55 Gb and annotated 22,487 genes. Comparative genomic analysis reveals specific gene family expansions or reductions that are associated with the formation of adhesive setae, nocturnal vision and tail regeneration, as well as the diversification of olfactory sensation. The obtained genomic data provide robust genetic evidence of adaptive evolution in reptiles.

Protein expression profiling during wallerian degeneration after rat sciatic nerve injury.

INTRODUCTION: Wallerian degeneration (WD) is an important area of research in modern neuroscience. Many protein expressions are regulated by differentially expressed genes in WD, but the precise mechanisms are elusive. METHODS: In this study, we profiled differentially expressed proteins in WD after rat sciatic nerve injury using an antibody array. RESULTS: Functional analysis positively identified cell proliferation, regulation of cell proliferation, and immune system processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed molecular networks related mainly to cytokine-cytokine receptor interaction, the mitogen-activated proteinkinase (MAPK) signaling pathway, apoptosis, the toll-like receptor (TLR) signaling pathway, and the Janus kinase (Jak) - signal transducer and activator of transcription (STAT) signaling pathway. Interactions between these differential proteins were well established and regulated by the key factors transforming growth factor beta 1 (TGF-ß1), toll-like receptor 4 (TLR4), Fas ligand (FasL), and 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1). CONCLUSIONS: These results provide information related to functional analysis of differentially expressed genes during WD.

Expression changes and bioinformatic analysis of Wallerian degeneration after sciatic nerve injury in rat.

Wallerian degeneration (WD) remains an important research topic. Many genes are differentially expressed during the process of WD, but the precise mechanisms responsible for these differentiations are not completely understood. In this study, we used microarrays to analyze the expression changes of the distal nerve stump at 0, 1, 4, 7, 14, 21 and 28 days after sciatic nerve injury in rats. The data revealed 6 076 differentially-expressed genes, with 23 types of expression, specifically enriched in genes associated with nerve development and axonogenesis, cytokine biosynthesis, cell differentiation, cytokine/chemokine production, neuron differentiation, cytokinesis, phosphorylation and axon regeneration. Kyoto Encyclopedia of Genes and Genomes pathway analysis gave findings related mainly to the MAPK signaling pathway, the Jak-STAT signaling pathway, the cell cycle, cytokine-cytokine receptor interaction, the p53 signaling pathway and the Wnt signaling pathway. Some key factors were NGF, MAG, CNTF, CTNNA2, p53, JAK2, PLCB1, STAT3, BDNF, PRKC, collagen II, FGF, THBS4, TNC and c-Src, which were further validated by real-time quantitative PCR, Western blot, and immunohistochemistry. Our findings contribute to a better understanding of the functional analysis of differentially-expressed genes in WD and may shed light on the molecular mechanisms of nerve degeneration and regeneration.

Signal flow and pathways in response to early Wallerian degeneration after rat sciatic nerve injury.

Wallerian degeneration (WD) remains a subject of critical research interest in modern neurobiology. WD is a process which a large number of genes are differentially regulated, especially the early response to activate nerve degeneration and regeneration, but the precise mechanisms remain elusive. In this study, we report the signal pathways, key regulate recurrent neural networks and signal flow in the early WD. The data indicated that there are several kinds of up- or down-regulated genes, relating to the regulation of response to stimulus, signal transmission via phosphorylation event, immune response, apoptosis and regulation of cell communication. KEGG pathway analysis revealed activity mainly relating to cytokine-cytokine receptor interaction, MAPK signaling pathway, Jak-STAT signaling pathway, ErbB signaling pathway and TGF-beta signaling pathway involved in the recurrent neural networks that were regulated by the key factors, Cldn-14, Cldn-15, ITG, BID and BIRC3. These results will help to much better understand information relating to the early response to WD and provide us with a firmer basis in future investigations on the molecular mechanisms of WD that regulate nerve degeneration and/or regeneration.

iTRAQ-coupled 2D LC-MS/MS analysis on differentially expressed proteins in denervated tibialis anterior muscle of Rattus norvegicus.

To understand the molecular aspects of denervation-induced atrophy of skeletal muscles, isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional liquid chromatography-tandem mass spectrometry were performed to detect a total of 260 proteins that were differentially expressed in the rat tibialis anterior muscle at different times (1, 4, and 8 weeks) after rat sciatic nerve transection. Western blot, gene ontology, and Kyoto Encyclopedia of Genes and Genomes analyses were further conducted for protein validation, functional annotation, and pathway identification, respectively. Among 260 dysregulated proteins, metabolic enzymes represented the largest class of proteins differentially expressed; a down-regulation of ß-enolase might be associated with a decreased expression of fast-twitch myosin-4; the 14-3-3 proteins displayed an up-regulation, which might facilitate the inhibition of mTOR signaling; an up-regulation of α-crystallin B chain might be related to the later onset and the slower progress of atrophy; an up-regulation of phosphatidylethanolamine-binding protein-1 perhaps progressively abrogated the cell survival and antiapoptotic properties during muscle atrophy. These results might contribute to the understanding of molecular mechanisms regulating denervation-induced muscle atrophy.

Gene expression profiling of the rat sciatic nerve in early Wallerian degeneration after injury.

Wallerian degeneration is an important area of research in modern neuroscience. A large number of genes are differentially regulated in the various stages of Wallerian degeneration, especially during the early response. In this study, we analyzed gene expression in early Wallerian degeneration of the distal nerve stump at 0, 0.5, 1, 6, 12 and 24 hours after rat sciatic nerve injury using gene chip microarrays. We screened for differentially-expressed genes and gene expression patterns. We examined the data for Gene Ontology, and explored the Kyoto Encyclopedia of Genes and Genomes Pathway. This allowed us to identify key regulatory factors and recurrent network motifs. We identified 1 546 differentially-expressed genes and 21 distinct patterns of gene expression in early Wallerian degeneration, and an enrichment of genes associated with the immune response, acute inflammation, apoptosis, cell adhesion, ion transport and the extracellular matrix. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed components involved in the Jak-STAT, ErbB, transforming growth factor-ß, T cell receptor and calcium signaling pathways. Key factors included interleukin-6, interleukin-1, integrin, c-sarcoma, carcinoembryonic antigen-related cell adhesion molecules, chemokine (C-C motif) ligand, matrix metalloproteinase, BH3 interacting domain death agonist, baculoviral IAP repeat-containing 3 and Rac. The data were validated with real-time quantitative PCR. This study provides a global view of gene expression profiles in early Wallerian degeneration of the rat sciatic nerve. Our findings provide insight into the molecular mechanisms underlying early Wallerian degeneration, and the regulation of nerve degeneration and regeneration.