Pore Size of 3D-Printed Polycaprolactone/Polyethylene Glycol/Hydroxyapatite Scaffolds Affects Bone Regeneration by Modulating Macrophage Polarization and the Foreign Body Response.

3D-printed porous bioactive ceramic scaffolds have been widely used in bone defect repair. However, material implantation is often accompanied by a foreign body response (FBR), which may affect host tissue regeneration. The physical properties of biomaterials, including shape, pore size, and porosity, control the relevant immune responses during tissue regeneration. To the best of our knowledge, the effect of the pore size of 3D-printed scaffolds on the immune response and bone-biomaterial integration has not been studied in vivo. Polycaprolactone/polyethylene glycol/hydroxyapatite (PCL/PEG/HA) bioactive scaffolds with different pore sizes, including 209.9 ± 77.1 µm (P200), 385.5 ± 28.6 µm (P400), and 582.1 ± 27.2 µm (P600), were prepared with a pneumatic extrusion 3D printer. Compared with other pore sizes, P600 significantly reduced the FBR and induced more M2 macrophage infiltration, vascular ingrowth, and new bone formation. Immunohistochemical staining revealed that the MyD88 protein might be involved in macrophage polarization-related signal transduction in response to the pore size. Based on these results, bone regeneration requires the active participation of the immune response, and the P600 PCL/PEG/HA scaffold is a preferable candidate for the repair of bone defects.

Huge solitary necrotic nodule of the liver: a rare case report with review of literature.

Solitary necrotic nodule of the liver (SNNL) is an uncommon disease in clinical practice, and its pathogenesis is still unclear. Here, we report the case of a 35-year-old woman. After physical examination, the patient was found to have a liver neoplasm, and there were no other physical complaints. Abdominal contrast-enhanced computed tomography (CT) showed the presence of a hypodense lesion. The patient opted for surgery to eliminate the lesion. Pathologic examination revealed an isolated necrotic nodular lesion with a size of 12 cm×10 cm×10 cm. The patient had a history of hepatitis B infection. To our knowledge, this is the largest SNNL ever reported and the first case with a history of hepatitis B infection.

Two different patients with pulmonary pleomorphic carcinoma response to PD-1 inhibitor plus anlotinib.

Pulmonary pleomorphic carcinoma (PPC) is a rare and highly malignant subtype of non-small-cell lung cancer (NSCLC), and chemotherapy and radiotherapy are insensitive. Some clinical trials have shown that targetable driver gene mutations, such as EGFR, ALK or BRAF, have rarely been detected in PPC patients, but the incidence of MET exon 14 mutations is more frequent. For these patients with driver gene mutations, corresponding molecular targeted therapy may be valid. In addition, limited cases have suggested that immunotherapy may be effective for PPC without sensitising EGFR or ALK alterations, but the efficacy in patients with other driver mutations remains unclear. Herein, we reported two PPC patients with different targetable gene mutations who both responded dramatically to the PD-1 inhibitor camrelizumab combined with the oral anti-angiogenic drug anlotinib: one harbouring a BRAF V600E mutation with positive PD-L1 expression, few tumour-infiltrating lymphocytes (TILs) and abundant tumour blood vessels; and the other exhibiting a MET exon 14 skipping mutation with PD-L1 overexpression, scattered TILs and abundant tumour blood vessels. Our findings suggest that PD-1 inhibitor combined with anlotinib may be a potential treatment for PPC patients, and abundant tumour vessels should be investigated as a possible therapeutic biomarker.

Long noncoding RNA MINCR regulates cellular proliferation, migration, and invasion in hepatocellular carcinoma.

PURPOSE: Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are aberrantly expressed in many cancer types, including hepatocellular carcinoma (HCC). lncRNA MYC-induced long non-coding RNA (MINCR) were revealed to be markedly up-regulated in gallbladder cancer and Burkitt lymphoma cells. However, the biological role and function of MINCR in HCC progression are still unknown. METHODS: The expression of MINCR in HCC tissues and cell lines was determined using quantitative real-time polymerase chain reaction assays. The effects of MINCR in HCC cell proliferation, migration, and invasion were determined using cell-counting kit 8 (CCK8) assay, wound healing assay, and Transwell assays in vitro. RESULTS: MINCR expression was up-regulated in HCC tissues and cell lines as compared with that in the negative control. The decreased expression of MINCR in vitro markedly inhibited HCC cell proliferation, migration, and invasion. Our results showed that MINCR is important in HCC development and may act as a therapeutic target that regulates HCC cellular proliferation, migration, and invasion, which are involved in HCC tumorigenesis. CONCLUSIONS: To the best of our know ledge, MINCR in HCC has not been studied. Our findings showed that this study is the first to reveal that MINCR may act as a therapeutic target in HCC. The in-depth exploration of the molecular mechanism is required to illuminate the molecular mechanisms of MINCR in HCC development.

Long noncoding RNA PCAT-1 promotes invasion and metastasis via the miR-129-5p-HMGB1 signaling pathway in hepatocellular carcinoma.

OBJECTIVE: The long non-coding RNA (lncRNA) prostate cancer-associated transcript 1(PCAT-1) has been shown to be dysregulated and exert vital roles in tumorigenesis and progression of various malignancies. However, the precise molecular mechanism in the metastasis and invasion of HCC remain unclear. METHODS: The expression levels of PCAT1 derived from human HCC tissues and cell lines were analyzed through quantitative real-time PCR. QRT-PCR was also applied to detect the expression of HMGB1 and miR-129-5p. Wound healing assay and transwell assays were performed to analyze cell migration and invasion ability. The mRNA levels and protein expression of HMGB1 were detected by western-blotting analysis and immunohistochemistry, respectively. Luciferase assays were used to investigate binding seeds beteen miRNA-129-5p and other transcripts, such as PCAT-1, HMGB1. RESULT: In this study, our founding demonstrated that PCAT-1 was not only aberrantly upregulated in HCC tissues and cell lines, but also associated with TNM stage, metastasis and Histological grade. In vitro, downregulation of PCAT-1 could reduce the invasion and migration of HCC cells. Moreover, our results showed that PCAT-1 could act as an endogenous RNA by directly binding to miR-129-5p. In addition, Luciferase reporter assay and western blotting analyses showed that PCAT-1 repressed inhibitory effect of miR-129-5p and reverse high mobility group box 1 (HMGB1) expression, a target gene of miR-129-5p. CONCLUSION: PCAT-1 functions as competing endogenous RNA (ceRNA) to provide a better understanding for HCC metastasis, and serves as a potential diagnostic and therapeutic target via PCAT-1/miR-129-5p/HMGB1 regulatory crosstalk for the deadly disease.

Special AT-rich DNA-binding protein-1 expression is associated with liver cancer metastasis.

To aim of the present study was to investigate the association between special AT-rich DNA-binding protein-1 (SATB1) expression and liver cancer metastasis. SATB1 mRNA and protein expression in hepatocellular carcinoma tissues was analyzed by immunohistochemistry, and in two hepatocellular cancer cell lines, MHCC-97H (high metastatic potential) and HepG2 (low metastatic potential), by reverse transcription-polymerase chain reaction and western blot analysis. Transwell migration and wound-healing assays were also performed to investigate the metastasis of liver cancer following upregulation or silencing of SATB1 expression. The results revealed that SATB1 expression was significantly higher in hepatocellular carcinoma tissues compared with carcinoma-adjacent tissues. Furthermore, SATB1 expression was correlated with tumor size, differentiation degree, hemorrhage and/or necrosis, invasion and/or metastases and TNM stage. Both the mRNA and protein expression of SATB1 was higher in MHCC-97H cells than HepG2 cells. In addition, the migration capability of MHCC-97H cells was decreased after SATB1 silencing, whereas the migration capability of HepG2 cells was increased after SATB1 upregulation. SATB1 expression was demonstrated to be positively correlated with liver cancer metastasis. These results indicate that liver cancer metastasis is regulated by SATB1 expression. Thus, immunohistochemical SATB1 expression may present an independent risk factor for the metastasis of liver cancer.

Diabetes mellitus potentiates diffuse large B­cell lymphoma via high levels of CCL5.

There is much evidence suggesting that CCL5 is one of the chemoattractant cytokines involved in diabetes mellitus (DM) with diffuse large B­cell lymphoma (DLBCL). However, the pathological impact is unclear. In the current study, in order to improve understanding regarding the role of CCL5 in DM with DLBCL, the expression levels of CCL5 mRNA were examined in normal B cells, human DLBCL cell lines (Ly1, Ly8 and Ly10) and a mouse DLBCL cell line (A20), as well as those in cells cultured with either 5 or 30 mmol/l glucose. A20­CCL5+ (CCL5 overexpression) and A20­CCL5­ (CCL5 knockdown) subclones were obtained through cell transduction with a lentiviral vector, and were subcutaneously injected into BALB/c DM mice and normal mice. Tumor growth was observed by calculating the tumor volume. The results demonstrated that CCL5 mRNA levels in DLBCL cells were significantly higher than those in the normal cells (P<0.05); and levels in DLBCL cells in 30 mmol/l Glu were significantly higher than in those of DLBCL cells in 5 mmol/l Glu (P<0.05). A20­CCL5+ cells led to tumor formation in DM mice compared with A20 and A20­CCL5­ cells. These results indicate that high levels of CCL5 expression may accelerate DLBCL formation in DM.