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BACKGROUND: We performed a bioinformatics analysis to screen for cell cycle-related differentially expressed genes (DEGs) and constructed a model for the prognostic prediction of patients with early-stage lung squamous cell carcinoma (LSCC). METHODS: From a gene expression omnibus (GEO) database, the GSE157011 dataset was randomly divided into an internal training group and an internal testing group at a 1:1 ratio, and the GSE30219, GSE37745, GSE42127, and GSE73403 datasets were merged as the external validation group. We performed single-sample gene set enrichment analysis (ssGSEA), univariate Cox analysis, and difference analysis, and identified 372 cell cycle-related genes. Additionally, we combined LASSO/Cox regression analysis to construct a prognostic model. Then, patients were divided into high-risk and low-risk groups according to risk scores. The internal testing group, discovery set, and external verification set were used to assess model reliability. We used a nomogram to predict patient prognoses based on clinical features and risk values. Clinical relevance analysis and the Human Protein Atlas (HPA) database were used to verify signature gene expression. RESULTS: Ten cell cycle-related DEGs (EIF2B1, FSD1L, FSTL3, ORC3, HMMR, SETD6, PRELP, PIGW, HSD17B6, and GNG7) were identified and a model based on the internal training group constructed. From this, patients in the low-risk group had a higher survival rate when compared with the high-risk group. Time-dependent receiver operating characteristic (tROC) and Cox regression analyses showed the model was efficient and accurate. Clinical relevance analysis and the HPA database showed that DEGs were significantly dysregulated in LSCC tissue. CONCLUSION: Our model predicted the prognosis of early-stage LSCC patients and demonstrated potential applications for clinical decision-making and individualized therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Studies have shown that P3H4 is a key gene underlying the malignant progression of LUAD. A potential biomarker and therapeutic target, P3H4 is involved in various cancers, but its molecular mechanism in LUAD remains unclear. Based on a series of experiments, we found that it significantly promoted the metastasis and proliferation of LUAD in vivo and in vitro. Lung cancer is associated with the greatest number of cancer-related deaths worldwide. Lung adenocarcinoma (LUAD) accounts for 85% of all cases of lung cancer. Despite recent advances in treatment, the 5-year survival rate remains less than 15%. Thus, the diagnostic and therapeutic role of LUAD remain to be further studied. The prolyl 3-hydroxylase family member 4 (P3H4) is involved in various cancers, but little is known about its role in LUAD. Our study demonstrated that the P3H4 gene was upregulated in LUAD. Clinically, the expression of P3H4 was positively correlated with an advanced TNM stage and shorter survival. Functionally, P3H4 plays a significant role in the metastasis and proliferation of LUAD both in vitro and in vivo. Mechanistically, P3H4 might interact with EGFR to regulate the metabolic substances. Our study indicated that P3H4 is a critical gene in the malignant progression of LUAD and represents a potential biomarker and therapeutic target. [ABSTRACT FROM AUTHOR]

Olfactory ensheathing cells (OECs) serve as a bridge by migrating at the site of spinal cord injury (SCI) to facilitate the repair of the neural structure and neural function. However, OEC migration at the injury site not only faces the complex and disordered internal environment but also is closely associated with the migration ability of OECs. We extracted OECs from the olfactory bulb of SD rats aged <7 days old. We verified the micro ribonucleic acid (miR)-145a-5p expression level in the gene chip after SCI and OEC transplantation using quantitative reverse transcription (qRT)-polymerase chain reaction (PCR). The possible target gene Plexin-A2 of miR-145a-5p was screened using bioinformatics and was verified using dual-luciferase reporter assay, Western blot, and qRT-PCR. The effect of miR-145a-5p/plexin-A2 on OEC migration ability was verified by wound healing assay, Transwell cell migration assay, and immunohistochemistry. Nerve repair was observed at the injured site of the spinal cord after OEC transplantation using tissue immunofluorescence and magnetic resonance imaging, diffusion tensor imaging, and the Basso–Beattie–Bresnahan locomotor rating scale were further used for imaging and functional evaluation. miR-145a-5p expression in the injured spinal cord tissue after SCI considerably decreased, while Plexin-A2 expression significantly increased. OEC transplantation can reverse miR-145a-5p and Plexin-A2 expression after SCI. miR-145a-5p overexpression enhanced the intrinsic migration ability of OECs. As a target gene of miR-145a-5p, Plexin-A2 hinders OEC migration. OEC transplantation overexpressing miR-145a-5p after SCI can increase miR-145a-5p levels in the spinal cord, reduce Plexin-A2 expression in the OECs and the spinal cord tissue, and promote OEC migration and distribution at the injured site. OEC transplantation overexpressing miR-145a-5p can promote the repair of neural morphology and neural function. Our study demonstrated that miR-145a-5p could promote OEC migration by down-regulating the target gene Plexin-A2, and transplantation of miR-145a-5p engineered OECs was beneficial to enhance neural structural and functional recovery in SCI rats. • miR-145a-5p/Plexin-A2 promote migration of OECs. • miR-145a-5p engineered OECs promotes functional recovery of SCI rats. [ABSTRACT FROM AUTHOR]

Panax japonicus C. A. Meye (PJ) has unique effects on diseases by "qi" stagnation and blood stasis in ancient. Modern studies have shown that PJ can treat diabetic kidney disease (DKD) caused by deficiency and blood stasis. This study evaluated the potential effects of PJ on DKD, a microvascular complication, and investigated its possible mechanisms. In this study, the chemical constituents of PJ were analyzed by HPLC. In vivo studies, we constructed a diabetic mice model by HDF combined with STZ, then administered PJ to diabetic mice for 6 weeks. Blood lipid, BUN, 24h urine protein, and renal tissue HE staining were detected to comprehensively evaluate the protective effect of PJ on DKD. Metabolomics investigated the metabolic pathways influenced by PJ in the treatment of DKD. Moreover, the potential targets and signal pathways were investigated using network pharmacology. Finally, molecular docking predicts affinity of active compounds and core targets, and western blotting was used to detect core target expression levels. In vivo study, PJ can reduce hyperlipidemia, serum BUN, and 24-h urinary protein in diabetic mice, and protect the pathological changes in renal tissue. Metabolomics results showed that PJ had significant regulatory effect on unsaturated fatty acids, glycerophospholipid metabolism, and purine metabolism. Network pharmacology showed that MAPK1, MAPK8, Bcl-2, and Caspase 3 were the core targets in PJ against DKD. Molecular docking revealed that Bcl-2 and Caspase 3 have a strong affinity for Chikusetsusaponin Iva, Ginsenoside Rb1, and Ginsenoside Rg1. Moreover, when compared to the model group, the PJ group had higher levels of anti-apoptosis protein Bcl-2 and lower levels of pro-apoptosis protein Caspase 3. PJ can reduce blood lipids, regulate the biosynthesis of unsaturated fatty acids and purine metabolism, thereby alleviating the renal injury of diabetic mice. Moreover, it can regulate the Bcl-2/caspase 3 apoptosis signaling pathway to prevent the apoptosis of renal cells and protect the renal function of diabetic mice. [Display omitted] • Panax japonicus can alleviate renal ectopic fat deposition to protect renal function in diabetic mice. • Panax japonicus involved glycerophospholipid metabolism and biosynthesis of unsaturated fatty acids in diabetic mice to protect renal function. • Panax japonicus can prevent the progression of diabetic kidney disease via anti-apoptosis in HDF combined with STZ-induced diabetic mice. [ABSTRACT FROM AUTHOR]

[Display omitted] • We employ a synthetic hybrid that mimics natural bone development but which employs PEKK in place of collagen. • The synthetic hybrid was made by using nanostructured Al2O3 and HA as seedbeds to grow PEKK molecules onto them. • HA hybrids increase the number of S-phase cells by elevating both mRNA and protein levels of cell cycle. • HA hybrids and S-PEKK/Al 2 O 3 promote cellular osteogenic differentiation by upregulating mRNA and protein expression of osteogenic-related genes. PEKK has good biocompatibility as an implantable material, but its mechanical properties and osseointegration are not satisfied enough. Aluminum oxide (Al 2 O 3) is highly wear-resistant, while hydroxyapatite (HA) is a biologically active. However all previous biocomposites made via mechanical mixing of these two bioceramic materials have not been able to meet clinical standards. The aim of this work is to resolve these problems by using newly synthesized bioceramic hybrids. In vitro and in vivo experiments have demonstrated that these new biomaterials have significantly improved biocompatibility and biomechanical properties when compared to neat PEKK. Surface sulfonation of the hybrids also leads to further improvements of these two properties. S-PEKK/Al 2 O 3 and S-PEKK/HA promote MC3T3-E1 adhesion. PEKK/HA and S-PEKK/HA significantly promote cell proliferation by upregulating both mRNA and protein levels of cell cycle genes to facilitate cells shift from G0/G1 phase to S phase. PEKK/HA hybrids and S-PEKK/Al 2 O 3 promote cell differentiation by upregulating the expression of osteogenic differentiation genes and proteins. PEKK/HA, S-PEKK/Al 2 O 3 and S-PEKK/HA are able to strongly bind to the new bone and exhibit good in vivo osseointegration properties. We conclude that PEKK/HA, S-PEKK/Al 2 O 3 and S-PEKK/HA show good osteogenic ability, especially S-PEKK/HA, and could be promising materials for bone implants. [ABSTRACT FROM AUTHOR]