Breast cancer (BRCA) is a malignant tumor with a high incidence and poor prognosis in females. However, its pathogenesis remains unclear. In this study, based on bioinformatic analysis, we found that LINC00467 was highly expressed in BRCA and was associated with tumor metastasis and poor prognosis. The genomic and epigenetic analysis showed that LINC00467 may also be regulated by copy number amplification (CNA), chromatin openness, and DNA methylation. In vitro experiments showed that it could promote the proliferation, migration, and invasion of BRCA cells. Competitive endogenous RNA (ceRNA) regulatory network analysis and weighted gene coexpression network analysis (WGCNA) suggested that LINC00467 may play a role in signaling pathways of peroxisomal lipid metabolism, immunity, and others through microRNAs (miRNAs) targeting transforming growth factor beta 2 (TGFB2). In addition, copy number amplification and high expression of LINC00467 were associated with the low infiltration of CD8+ and CD4+ T cells. In conclusion, we found that LINC00467, driven by copy number amplification and DNA demethylation, may be a potential biomarker for the diagnosis and prognosis of BRCA and a tumor promoter acting as a potential therapeutic target for BRCA as well.

Excessive scars affect a patient's quality of life, both physically and psychologically, by causing pruritus, pain and contractures. Because there is a poor understanding of the complex mechanisms underlying the processes of hypertrophic scar formation, most therapeutic approaches remain clinically unsatisfactory. In this study, we found that miR-138 was downregulated and peroxisome proliferator-activated receptor (PPARβ) was inversely upregulated in hypertrophic scar tissues compared to in paired normal skin tissues. Using a dual-luciferase assay, we validated that miR138 directly targets PPARβ and regulates its expression at the transcriptional and translational levels. In gain-and-loss experiments, we found that miR-138/PPARβ signaling regulated human hypertrophic scar fibroblast proliferation and movement, and affected scarring-related protein expression, which suggests that miR-138/PPARβ signaling is important for hypertrophic scarring. Thus, our study provides evidence to help determine whether miR-138/PPARβ signaling may be a potential target for hypertrophic scarring management.

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Background Neuropathic pain belongs to chronic pain and is caused by the primary dysfunction of the somatosensory nervous system. Long noncoding RNAs (lncRNAs) have been reported to regulate neuronal functions and play significant roles in neuropathic pain. DLEU1 has been indicated to have close relationship with neuropathic pain. Therefore, our study focused on the significant role of DLEU1 in neuropathic pain rat models. Methods We first constructed a chronic constrictive injury (CCI) rat model. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were employed to evaluate hypersensitivity in neuropathic pain. RT-qPCR was performed to analyze the expression of target genes. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect the concentrations of interleukin‐6 (IL-6), tumor necrosis factor‐α (TNF-α) and IL-1β. The underlying mechanisms of DLEU1 were investigated using western blot and luciferase reporter assays. Results Our findings showed that DLEU1 was upregulated in CCI rats. DLEU1 knockdown reduced the concentrations of IL‐6, IL‐1β and TNF‐α in CCI rats, suggesting that neuroinflammation was inhibited by DLEU1 knockdown. Besides, knockdown of DLEU1 inhibited neuropathic pain behaviors. Moreover, it was confirmed that DLEU1 bound with miR-133a-3p and negatively regulated its expression. SRPK1 was the downstream target of miR-133a-3p. DLEU1 competitively bound with miR-133a-3p to upregulate SRPK1. Finally, rescue assays revealed that SRPK1 overexpression rescued the suppressive effects of silenced DLEU1 on hypersensitivity in neuropathic pain and inflammation of spinal cord in CCI rats. Conclusion DLEU1 regulated inflammation of the spinal cord and mediated hypersensitivity in neuropathic pain in CCI rats by binding with miR-133a-3p to upregulate SRPK1 expression.

Hypertrophic scar (HTS) is a complicated pathological process induced mainly by burns and wounds, with abnormal proliferation of fibroblasts and the transformation of fibroblasts to myofibroblasts. PAPPA-AS1, a differentially expressed long noncoding RNA (lncRNA) in the HTS tissues, attracted our interests in its potential role and mechanism in the development and process of HTS. In the present study, the regulatory effect of lncRNA PAPPA-AS1 on the Toll-like receptor 4 (TLR4) signal pathway, as well as the molecular mechanism, was investigated. Bioinformatics analysis was utilized to screen the differentially expressed lncRNAs in HTS tissues. PAPPA-AS1 was significantly upregulated in both HTS tissues and hypertrophic scar fibroblast (HTsFb) cells. The expression levels of TLR4, MyD88, TGF-β1, collagen I, collagen III, and α-SMA were greatly elevated in HTsFb cells. By knocking down PAPPA-AS1, the proliferation of HTsFb cells, TLR4, and TGF-β1 signal pathway and the expression of fibrosis markers both in HTsFb cells and HTS tissues were suppressed. It was accompanied by the alleviated pathological state in the HTS tissues, which were significantly reversed by cotransfecting with the pcDNA3.1-TLR4 vector. Positive correlation and interaction were observed between PAPPA-AS1 and TAF15 and between TAF15 and the promoter of TLR4, respectively. In conclusion, lncRNA PAPPA-AS1 might induce the development of HTS by upregulating TLR4 through interacting with TAF15.

Malignant melanoma is one of the most leading forms of skin cancer associated with a low patient survival rate. There is an urgent need to illustrate risk factors that can trigger the motility of melanoma cancer cells. Our present study revealed that mono-(2ethylhexyl)phthalate (MEHP) exposure can significantly increase the in vitro migration and invasion of WM983A and A375 cells. Among the tested cytokines, MEHP can increase the expression of transforming growth factor β (TGF-β). Inhibition of TGF-β via its neutralization antibody can attenuate MEHP-induced cell migration and invasion. Further, upregulation of TGF-β mediated MEHP-induced activation of Smad signals and upregulation of Snail in melanoma cells. Blocking the TGF-β/Smad signal pathway can attenuate MEHP-induced cell migration. Estrogen receptor α (ERα) was essential for MEHP-induced expression of TGF-β. In addition, MEHP can increase the expression of ERα in melanoma cells. Collectively, our study found that MEHP can stimulate the progression of melanoma via TGF-β signals. Significance: Mono-(2-ethylhexyl)phthalate (MEHP) is the active and most toxic metabolite of di(2-ethylhexyl)phthalate (DEHP). Our present study revealed that MEHP can trigger the in vitro migration and invasion of melanoma cells via upregulation of TGF-β/Snail signals. It revealed that daily exposure to MEHP might be a risk factor for melanoma patients.

Background A low survival rate is one of the main challenges in fat grafting. Objectives This study aimed to evaluate whether the microfat obtained using a novel strategy promoted the survival and retention of fat grafts. Methods A 5 mm diameter blunt tip cannula with larger side holes (~30 mm 2 per hole) was used to obtain macrofat. Subsequently, a novel strategy based on a newly invented extracorporeal cutting device was used to cut the macrofat into microfat, which was named adipose-derived progenitor cells enrichment fat (AER fat); Coleman fat was used as the control. Aliquots (0.5 mL) of both groups of fat were transplanted into 10 nude mice and analyzed 10 weeks later. Western blotting, flow cytometry, and immunofluorescence were performed to assess the AER characteristics and underlying mechanisms. Results The retention rate of fat grafts in AER fat-treated animals was significantly higher than that in the Coleman group (54.6±13% vs. 34.8±9%, P<0.05) after 10 weeks. AER fat contained more DPP4 + progenitor cells (3.3±0.61×10 3 vs. 2.0±0.46×10 3 cells/mL, P<0.05), adipose-derived plastic-adherent cells (6.0±1.10×10 4 vs. 2.6±0.17×10 4 cells/mL, P<0.001), and viable adipocytes as compared to Coleman fat. Moreover, histological analysis showed that AER fat graft had better histological structure and higher capillary density. Conclusions AER fat transplantation is a potential strategy to improve the survival and long-term retention of fat grafts. AER fat contained more DPP4 + progenitor cells.

Titanium cranioplasty is one of the well-established and widely used techniques for repairing cranial defects. In this paper, we present an improved way to design and create titanium meshes with more evaluation process. Computed tomography scan data of patients were used to create three-dimensional virtual models. Implants were designed with NX ImageWare 13.2 (Siemens PLM Software, Plano, TX). Final titanium meshes were assessed by Geomagic Studio 12 (Geomagic, Inc., Morrisville, NC) and NX ImageWare 13.2.Titanium meshes were designed and applied to cranioplasty surgery on 8 patients. Postoperative results were evaluated by computed tomography scanning and further analyzed with rainbow difference tomography. All patients were satisfied with the outcome. With this method, surgeons, engineers, and patients work together to evaluate and edit implant design. Our method provides better communication and comprehensive evaluation, which result in a satisfying outcome.