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Introduction Mast cells are regarded as a kind of classical anaphylaxis cells. However autoimmune diseases and allergic reactions have many similarities or overlaps. A large number of papers have proved that mast cells play a significant role in the pathogenesis of systemic lupus erythematosus (SLE). It is speculated that IgE, anti‐IgE antibodies, FcεRI, and anti‐FcεRI antibodies activate mast cells through autoimmune pathways and participate in the disease process of SLE. Naturally occurring protein molecules not only exist in monomer form, but also in polymer of protein molecules. Therefore, whether IgE, FcεRIα, anti‐IgE antibodies, and anti‐FcεRI antibodies also exist in polymeric forms in the natural state is worthy of further investigation. Methods The serum samples and clinical data of 131 patients with SLE were collected from Qilu Hospital (Qingdao). Sixty healthy individuals were collected as the control group. Serum FcεRIα, anti‐IgE, and anti‐FcεRI were detected by enzyme‐linked immunosorbent assay. Serum IgE was detected by rate scatter nephelometry. A Chinese hamster ovarian cancer cell line CHO3D10 transfected with human FcεRIα was cultured and the cell protein extract was prepared. The existence forms of FcεRIα in the cell protein extract were detected by the native‐page method. Results The serum FcεRIα in SLE patients was significantly higher than that in control group (3.52 [2.18, 4.71] µg/ml and 1.87 [1.52, 2.33] µg/ml, respectively; p, First, as autoimmune diseases and allergic reactions have many similarities or overlaps, we compared the differences in serum IgE, FcεRIα, anti‐IgE, and anti‐FcεRI levels of systemic lupus erythematosus group and healthy control group for the first time. The serum FcεRIα in SLE patients is significantly higher than that in the control group and anti‐IgE is significantly lower than that in the control group, which provides a new reference basis for the understanding and further discussion of the inflammatory mechanism of the disease. Second, this study has revealed that the FcεRIα has one kind of monomer and two kinds of polymers in the degeneration conditions, which is worthy of further investigation.

Backgrounds Salivary biomarkers hold huge potential for the non-invasive diagnosis of oral squamous cell carcinoma. Angiogenic factors and matrix-metalloproteinases (MMPs) are highly expressed in OSCC tissue, but their expression patterns in the saliva are unknown. This study aimed to analyze the levels of angiogenic factors and MMPs in tumor tissue and saliva of OSCC patients. Methods OSCC-tissue, adjacent normal tissue (ANT), saliva from OSCC patients, and healthy controls were obtained. The expression patterns of angiogenic factors and MMPs were analyzed by immunohistochemistry, protein chip array, and RT-qPCR. Results Results showed higher expression of ANG, ANG-2, HGF, PIGF, VEGF, MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, TIMP-1, and TIMP-2 in OSCC-tissues compared to the ANT. Among the overexpressed markers in OSCC-tissues, HGF, VEGF, PIGF, PDGF-BB, MMP-1, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, and TIMP-2 were significantly upregulated in the saliva of OSCC patients compared to healthy controls. Conclusions The levels of HGF, VEGF, PIGF, MMP-1, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, and TIMP-2 were upregulated both in OSCC tissue and saliva of OSCC patients. Bioinformatic analysis revealed the correlation of these factors with patient survival and cancer functional states in head and neck cancer, indicating these factors as possible saliva-based non-invasive diagnostic/prognostic markers and therapeutic targets of OSCC.

In this study, a three-phased multiwalled scaffold, composed of carbon nanotube (mwCNT), nanocrystalline hydroxyapatite (nHA), and polycaprolactone (PCL), was fabricated by the solvent evaporation technique. The structure character, mechanical properties, and degradation activity in simulated body fluid (SBF), along with osteoproductive ability in human osteosarcoma cell MG63, were investigated thoroughly. Results showed that the three phases in mwCNT/nHA/PCL composite presented excellent miscibility and stronger interfacial force when the weight content was 1/15/84 (wt%). Simultaneously, the composite had smaller porosity and slower degradation rate, and there was massive crystallized hydroxyapatite formed on the surface after being soaked in SBF. With regard to bioactivity, MG63s on this scaffolds presented good proliferation performance and differentiated into the osteogenic lineage by expressing high levels of ALP. It was concluded that mwCNTs/nHA/PCL composite scaffolds might be beneficial for bone tissue engineering at a relatively low concentration of mwCNTs and nHA.

P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs), a novel class of noncoding RNAs, are involved in the carcinogenesis. However, the functional significance of piRNAs in oral squamous cell carcinoma (OSCC) remains unknown. In the present study, we used chemical carcinogen 4-nitroquinoline-1-oxide (4NQO) induced OSCC mouse model. piRNAs and mRNAs were profiled using next-generation sequencing in the tongue tumor tissues from 4NQO induction and healthy tongue tissues from control mice. Furthermore, we analyzed the differential gene expression of human OSCC in Gene Expression Omnibus (GEO) database. According to the common differentially expressed genes in the 4NQO model and human OSCC tissues, piRNAs and mRNAs network were established based on informatics method. A total of 14 known piRNAs and 435 novel predicted piRNAs were differently expressed in tumor tissue compared to healthy tissue. Among differently expressed piRNAs 260 were downregulated, and 189 were upregulated. The mRNA targets for the differentially expressed piRNAs were identified using RNAhybrid software. Primary immunodeficiency and herpes simplex infection were the most enriched pathways. A total of 22 mRNAs overlapped in human and mice OSCC. Moreover, we established the regulatory network of 11 mRNAs, including Tmc5, Galnt6, Spedf, Mybl2, Muc5b, Six31, Pigr, Lamc2, Mmp13, Mal, and Mamdc2, and 11 novel piRNAs. Our data showed the interaction between piRNAs and mRNAs in OSCC, which might provide new insights in the development of diagnostic biomarkers and therapeutic targets of OSCC.

Endometrial cancer (EC) is one of the most common malignant gynecological tumors in women. The main treatments for EC (surgery, chemotherapy and radiation therapy) produce significant side effects. Thus, it is urgent to identify promising therapeutic targets and prognostic markers. CACNA2D3, as a member of the calcium channel regulatory α2δ subunit family, is reported to exert a tumor suppressive effect in numerous cancers. However, the function of CACNA2D3 in EC is not well known. In the present study, CACNA2D3 was lowly expressed in EC tissues and cells. The overexpression of CACNA2D3 via lentiviral particle injection significantly blocked the tumor growth in an in vivo xenograft model. In vitro, the overexpression of CACNA2D3 markedly inhibited cell proliferation and migration, and promoted cell apoptosis and calcium influx. These data revealed that CACNA2D3 functions as a tumor suppressor in EC. It was also revealed that the addition of progesterone (P4) blocked tumor growth in Ishikawa‑injected nude mice. P4 induced the expression of CACNA2D3 in vivo and in vitro, and the silencing of CACNA2D3 affected P4‑inhibited cell proliferation and P4‑induced cell apoptosis and calcium influx. In Ishikawa cells, P4 enhanced the expression of phosphorylated (p)‑p38 MAPK and PTEN, but blocked the levels of p‑PI3K and p‑AKT. The knockdown of CACNA2D3 blocked the function of P4. These data revealed that P4 promoted cell apoptosis via the activation of the CACNA2D3/Ca2+/p38 MAPK pathway, and blocked cell proliferation via suppression of the PI3K/AKT pathway. Collectively, these findings indicated the antitumor role of CACNA2D3 in EC, and revealed the mechanism of P4 inhibition of EC progression, which provided a new target for EC therapy and new evidence for P4 in EC therapy.

Purpose: Metastasis is the hallmark of gastric cancer (GC) and is the most widely recognized reason for GC-related deaths. However, the underlying mechanism of GC metastasis remains unknown. Herein we sought to investigate the biologic function of Gpx3 in gastric tumor metastasis and the underlying mechanism. Methods: Cell migration and invasion was determined with Transwell chamber assay. Western blotting was used to determine protein expression levels of Gpx3, EMT markers and Wnt signaling related molecules. In vivo metastasis was determined with experiment lung metastasis model in tumor xenografts. Results: Gpx3 expression was lower in GC patients and GC cell lines when compared with normal tissues and cells. Further studies showed that overexpression of Gpx3 was able to inhibit GC cell migration and invasion whereas Gpx3 knockdown promoted cell migration and invasion. Furthermore, AGS cells overexpressing Gpx3 showed lower metastatic potential when compared with the parental cells. Gpx3 was also found to regulate the expression of EMT markers. Mechanistic study showed that Gpx3 selectively inhibited Wnt/JNK signaling pathway over canonical Wnt/β-catenin pathway. The data revealed that blockade of NFкB and JNK signaling pathway abolished siGpx3-induced cell migration and invasion. Conclusions: Taken together, we identify Gpx3 as a suppressor of GC metastasis. Above results provide the rationale that regulation of Gpx3 serves as a potential therapeutic option for GC.

Background: Hepatocellular carcinoma results in high cancer mortality and is difficult to eradicate because of its late stage at the time of diagnosis, multicentricity, and cirrhotic background. It is therefore urgent to explore effective and economical therapeutic methods to treat this disease. Objectives: We aimed to investigate the antitumor activity of exogenous opioid growth factor (OGF), as well as the effect of the combination of OGF and cisplatin on hepatocellular carcinoma. The possible underlying mechanisms were also explored. Materials and Methods: RT-PCR and immunohistochemistry were employed to determine the expression of OGF receptor (OGFr) in hepatocellular carcinoma. MTT assays were used to explore the effect of OGF on cell migration and proliferation. Animal experiments were performed to explore the effect of OGF and DDP on tumors. Results: OGFr is present in human HCC cells and was differentially expressed between HCC tumor and non-tumor tissues. OGF inhibited HCC cell proliferation and migration. The silencing of OGFr blocked the expression of p21 and p53. Treatment using OGF, DDP and OGF+DDP all suppressed the growth of HCC tumors, with the maximum effect in the OGF+DDP group. Conclusion: Our study clarified that OGF inhibits cell migration and proliferation of HCC in animal experiments and that exogenous OGF enhances the anti-tumor activity of cisplatin on HCC by upregulating p21 and p53. These findings may provide a new strategy for future HCC therapeutics.

Epithelial-mesenchymal transition (EMT) plays a crucial role in colorectal cancer (CRC) metastasis. Soluble E-cadherin (sE-cadherin) is a peptide degradation product of the E-cadherin, a key epithelial molecule of EMT. However, it is not known if elevated levels of sE-cadherin also occur during EMT. And the study of sE-cadherin in colorectal cancer is rare. The purpose of the study was to evaluate the relationship between sE-cadherin and EMT in CRC and to evaluate the diagnostic value of sE-cadherin as a serum marker for CRC. Transforming growth factor-β1 (TGF-β1) was used to induce EMT in HT29 and SW480 cells. The cells treated with TGF-β1 showed morphological and biological behavior changes consistent with EMT. Western blot and ELISA showed the levels of sE-cadherin were increased during EMT in CRC cells. In addition, we intravenously injected luciferase-labeled SW480 cells into nude mice to construct CRC metastasis model. Following the elongation of time, the fluorescence intensity of the experimental group was gradually increased. Correspondingly, the serum concentration of sE-cadherin also increased during CRC metastasis in mice. Furthermore, compared to healthy subjects, significantly higher levels of serum sE-cadherin were also observed in CRC patients and correlated with clinicopathological features. For discriminating CRC from healthy controls, the area under the receiver operating characteristic (ROC) curve (AUC) of sE-cadherin was 0.853, while the optimal cut-off point was set at 5928.16 ng/ml, the diagnostic sensitivity was 73.9% and the specificity was 80%. Compared with current commercial biomarkers (CEA, CA19-9 and CA125), the diagnostic performance of sE-cadherin was highest. Combined sE-cadherin and CEA raised the sensitivity to 82.4%. Serum sE-cadherin level can be used as a potential diagnostic biomarker of CRC.

Indirubin, a traditional Chinese medicine, is currently used to treat certain autoimmune diseases such as primary immune thrombocytopenia (ITP) in clinics. However, the effects of indirubin on expression of related genes in peripheral blood mononuclear cells (PBMCs) from ITP patients have not been investigated. In the present study, PBMCs were isolated from 19 adult patients with well-characterized active ITP and 20 healthy controls (HCs) and then treated with increasing concentrations of indirubin. The mRNA expression levels of thrombopoietin receptor (MPL), GATA binding protein 3 (GATA3), DNA methyltransferase 3B (DNMT3B), interleukin-6 (IL6), tumor necrosis factor (TNF), and interferon gamma (IFN-γ) were determined by quantitative real-time polymerase chain reaction (PCR). We found that indirubin had no cytotoxic effect on PBMC viability. Significantly lower MPL (p0.05) and GATA3 (p0.05) expression together with markedly higher IL6 (p0.05), TNF (p0.0001), and IFN-γ (p0.001) mRNA levels were observed in ITP patients compared with HCs. Notably, indirubin significantly enhanced MPL expression and inhibited TNF expression in PBMCs from ITP patients (p0.05). In summary, indirubin may play a direct role in thrombopoiesis by activating cellular MPL and normalizing TNF expression to suppress inflammation in ITP. This study may thus improve our understanding of indirubin and provide important information for optimizing therapeutic strategies for ITP patients.