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Root canal therapy has been the predominant approach in endodontic treatment, wherein the entire pulp is cleaned out and replaced with a gutta-percha filling. However, living pulp is critical for the maintenance of tooth homeostasis and essential for tooth longevity. An ideal form of therapy, therefore, might consist of regenerative approaches in which diseased/necrotic pulp tissues are removed and replaced with regenerated pulp tissues to revitalize the teeth. Dental pulp regeneration presents one of the most challenging issues in regenerative dentistry due to the poor intrinsic ability of pulp tissues for self-healing and regrowth. With the advent of modern tissue engineering and the discovery of dental stem cells, biological therapies have paved the way to utilize stem cells, delivered or internally recruited, to generate dental pulp tissues, where growth factors and a series of dentine extracellular matrix molecules are key mediators that regulate the complex cascade of regeneration events to be faithfully fulfilled.

Glioma is the most common malignant tumor in the central nervous system. This study aims to explore the potential mechanism and identify gene signatures of glioma. The glioma gene expression profile GSE4290 was analyzed for differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied for the enriched pathways. A protein-protein interaction (PPI) network was constructed to find the hub genes. Survival analysis was conducted to screen and validate critical genes. In this study, 775 downregulated DEGs were identified. GO analysis demonstrated that the DEGs were enriched in cellular protein modification, regulation of cell communication, and regulation of signaling. KEGG analysis indicated that the DEGs were enriched in the MAPK signaling pathway, endocytosis, oxytocin signaling, and calcium signaling. PPI network and module analysis found 12 hub genes, which were enriched in synaptic vesicle cycling rheumatoid arthritis and collecting duct acid secretion. The four key genes CDK17, GNA13, PHF21A, and MTHFD2 were identified in both generation (GSE4412) and validation (GSE4271) dataset, respectively. Regression analysis showed that CDK13, PHF21A, and MTHFD2 were independent predictors. The results suggested that CDK17, GNA13, PHF21A, and MTHFD2 might play important roles and potentially be valuable in the prognosis and treatment of glioma.

Departmental sources Background:The extent of glioma resection influences the overall survival (OS) and progression-free survival (PFS). Ferroptosis is a newly recognized type of cell death, which may be associated with low-grade glioma border detection and OS. This study is assessed an optimized ferroptosis gene panel for glioma treatment. Material/Methods:We obtained 45 reports on ferroptosis-related proteins in PubMed and conducted a statistical test of the patients' overall survival (OS) in the TCGA GBMLGG and CGGA databases. The statistically significant genes were screened for an optimal panel, followed by GO and KEGG analysis and evaluated its correlation with known prognostic factors of glioma, including IDH1 mutation, methylated MGMT, tumor purity, 1p/19q LOH, and methionine cycle. Results:Eight genes panel (ALOX5, CISD1, FTL, CD44, FANCD2, NFE2L2, SLC1A5, and GOT1) were highly related to OS (P<0.001) and PFS (P<0.001) of low-grade glioma (LGG) patients, out of which 6 genes (ALOX5, CISD1, CD44, FTL, FANCD2, and SLC1A5) were correlated with IDH1_p.R132H (P<0.001) and 5 genes (ALOX5, CD44, FTL, NFE2L2, SLC1A5) showed a correlation with tumor purity (P<0.001). Five genes (ALOX5, CD44, CISD1, FTL, and SLC1A5) were associated with methylated MGMT (P<0.001), out of which 6 genes (ALOX5, CD44, FANCD2, NFE2L2, SLC1A5, and GOT1) had significantly different expression in healthy brain tissue vs. glioma (P<0.001). Conclusions:Our panel of 8 ferroptosis genes showed a significant correlation with the diagnostic and prognostic factors of low-grade glioma and can be applied in neuroradiology and surgery.

Recently, studies on transcriptome-proteome relationships have revealed mRNA/protein expression discordance for certain genes and speculated that protein posttranslational modification (PTM) may be involved. However, there is currently no evidence to support this hypothesis. Wnt-induced secreted protein-1 (WISP1) is the downstream target gene of β-catenin and plays an important role in tumorigenesis and progression, but the expression and role of WISP1 in different tumor types are controversial. Here, we first confirmed that WISP1 protein expression was significantly down-regulated in hepatocellular carcinoma (HCC) tissue and could be an independent predictor of poor prognosis for patients with HCC. In vivo and in vitro evidence was provided that WISP1 can suppress HCC cell proliferation. Further studies have found that low WISP1 protein expression was related to expression of human leukocyte antigen F locus adjacent transcript 10 (FAT10), a specific ubiquitin-like protein with both degradation and stabilization functions, which plays an important role in PTM. FAT10 overexpression facilitated WISP1 degradation by FAT10ylation to decrease WISP1 protein expression, thus promoting HCC proliferation. Interestingly, we found and demonstrated that FAT10 overexpression could result in WISP1 protein/mRNA expression discordance, with protein expression decreasing while mRNA expression increased. The underlying mechanism is that FAT10 exerts substrate stabilization and degradation functions simultaneously, while FAT10 overexpression promotes WISP1 mRNA expression by stabilizing β-catenin and directly degrades WISP1 protein. Conclusion: Our study demonstrated that overexpression of FAT10 results in expression discordance between WISP1 protein and mRNA, thereby promoting HCC progression by down-regulating WISP1 protein expression.

Gliomasdevastating intracranial tumors with a dismal outcomeare in dire need of innovative treatment. Although nanodrugs have been utilized as a target therapy for certain types of solid tumors, their therapeutic effects in gliomas are limited due to the complications of the systemic circulation, blood–brain barrier (BBB), and specific glioma environment. Thus, we aimed to establish a nanoliposome adaptable to different environments by codelivery of shCD163 and doxorubicin (DOX) to treat gliomas. In this study, we first synthesized pH-sensitive DSPE-cRGD-Hz-PEG2000 to form an environmentally self-adaptative nanoliposome (cRGD-DDD Lip) via a thin film method. We used in vitro BBB models, in vitro cell uptake experiments, and in vivo biodistribution assays to confirm the long circulation time and low cell uptake of the cRGD-DDD Lip as a result of the poly­(ethylene glycol) (PEG) shell of cRGD-DDD Lip in the neutral pH systemic circulation. Moreover, the cRGD-DDD Lip bypassed the BBB and attached to the intracranial glioma following the removal of the PEG shell and the exposure of cRGD to the weakly acidic tumor microenvironment. We further assembled the shCD163/DOX@cRGD-DDD Lip through cRGD-DDD Lip loading of shCD163 and DOX. In vitro, cell proliferation and self-renewal of glioma cells were inhibited by the shCD163/DOX@cRGD-DDD Lip due to the toxicity of DOX and the suppression of shCD163 via the CD163 pathway. In vivo, the shCD163/DOX@cRGD-DDD Lip disturbed the progression of in situ gliomas by inhibiting the growth and stemness of glioma cells and prevented the recurrence of gliomas after resection. In conclusion, the cRGD-DDD Lip may be a promising nanodrug-loading platform to cope with different environments and the shCD163/DOX@cRGD-DDD Lip may potentially be a novel nanodrug for glioma therapy.

BackgroundInsulin resistance (IR) is involved in the pathogenesis of atherosclerosis. As a new indicator, the triglyceride-glucose (TyG) index has greater operability for the evaluation of insulin resistance. Previous studies have shown inconsistent results in evaluating the association between the TyG index and stroke incidence in people without stroke at baseline. Therefore, this study aimed to systematically assess this association through a meta-analysis.MethodsCohort studies with the multivariate-adjusted hazard ratio (HR) association between the TyG index and stroke were obtained by searching the PubMed, Cochrane Library, and EMBASE databases before 16 December 2021. We pooled the adjusted HR along with 95% CI using a random-effects model. The primary outcome was stroke including ischemic and hemorrhagic stroke. We conducted subgroup analyses stratified by study design, ethnicity, characteristics of participants, weight of studies, and length of follow-up duration. Review Manager 5.3 and Stata 17 were used to perform the meta-analysis.ResultsEight cohort studies with 5,804,215 participants were included. The results showed that participants with the highest TyG index category at baseline compared to those with the lowest TyG index category were independently associated with a higher risk of stroke (HR: 1.26, 95% CI: 1.24–1.29, I2 = 0%, P &lt; 0.001). This finding was consistent with the results of the meta-analysis with the TyG index analyzed as a continuous variable (HR per each-unit increment of the TyG index: 1.13, 95% CI 1.09–1.18, I2 = 0%, P &lt; 0.001). Subgroup analysis had no significant effects (for subgroup analysis, all P &gt; 0.05). No significant heterogeneity was observed among the included cohort studies.ConclusionA higher TyG index may be independently associated with a higher risk of stroke in individuals without stroke at baseline. The aforementioned findings need to be verified by a large-scale prospective cohort study to further clarify the underlying pathophysiological mechanism between the TyG index and stroke.