The aim of this study was to determine whether the serum level of irisin can be a candidate to predict the spinal metastasis in patients with breast cancer.In a cross-sectional study, 148 patients were recruited. Of those, 53 (35.8%) had spinal metastasis. The baseline characteristics were compared by status of spinal metastasis. Multiple logistic regression analysis was used to determine whether the serum irisin can be a candidate for predicting breast cancer to spinal metastasis. The correlation coefficient analysis was used to confirm the correlation between the serum irisin and lipid metabolic parameters and body mass index (BMI), respectively.The serum irisin was higher in patients without spinal metastasis (7.60 ± 3.80). Multivariable analysis showed that the serum irisin was protective to the presence of spinal metastasis in patients with breast cancer after adjustments of age and BMI (odds ratio, 0.873; 95% confidence interval, 0.764–0.999). Furthermore, there was a positive correlation between the serum irisin and BMI (r = 0.263). The patients with metabolisc syndrome (MetS) had a higher level in serum irisin. In addition, the higher numbers of MetS components were associated with higher serum irisin.Higher serum irisin can be a protective factor of spinal metastasis in patients with breast cancer. The BMI is positively associated with the serum level of irisin. Furthermore, patients with MetS tended to have a higher level of serum irisin.

JHDM1D antisense 1 (JHDM1D-AS1), a long non-coding RNA (lncRNA), has been shown to promote pancreatic cancer growth by inducing an angiogenic response. However, its biological and clinical significance in non-small-cell lung cancer (NSCLC) is still unclear. In this study, we examined the expression and prognostic significance of JHDM1D-AS1 in NSCLC. The effects of JHDM1D-AS1 knockdown or overexpression on NSCLC growth and metastasis were investigated. We show that JHDM1D-AS1 is upregulated in NSCLC relative to adjacent normal lung tissues. High JHDM1D-AS1 expression is significantly correlated with advanced tumor, node, and metastasis (TNM) stage and lymph node metastasis. JHDM1D-AS1 expression serves as an independent prognostic factor for overall survival of patients with NSCLC. Functionally, JHDM1D-AS1 knockdown inhibits NSCLC cell aggressiveness both in vitro and in vivo, which is rescued by ectopic expression of JHDM1D-AS1. JHDM1D-AS1 binding stabilizes DHX15 protein in NSCLC cells. DHX15 overexpression enhances NSCLC cell proliferation and invasion, whereas knockdown of DHX15 exerts opposite effects. JHDM1D-AS1-mediated aggressive phenotype is impaired when DHX15 is silenced. Ectopic expression of DHX15 restores the defects in proliferation and invasion of JHDM1D-AS1-depleted NSCLC cells. Collectively, the interaction between JHDM1D-AS1 and DHX15 accounts for NSCLC growth and metastasis. This work provides potential additional therapeutic targets for treatment of NSCLC.

Inflammasomes are protein complexes responsible for the release of IL-1 family cytokines, and they play critical roles in immunity and inflammation. The best-characterized inflammasome, the NOD-like receptor protein 3 (NLRP3) inflammasome, is involved in the development of multiple autoimmune diseases. However, the underlying mechanisms of abnormal NLRP3 inflammasome activation in systemic lupus erythematosus (SLE) remain elusive. Here, western blot analysis was used to detect the level of NLRP3 components and mTORC1/2 substrate in the kidney tissues from B6.MRL-FASlpr/J lupus mice and C57BL/6 mice, and the results showed that mammalian target of rapamycin (mTOR) complex 1/2 (mTORC1/2) and the NLRP3 inflammasome were hyperactivated in B6.MRL-FASlpr/J lupus mice. The inhibition of mTOR by INK128, a novel mTORC1/2 inhibitor, suppressed LPS/ATP and LPS/nigericin-induced NLRP3 inflammasome activation in bone marrow-derived macrophages (BMDMs) in vitro. INK128 decreased both the mRNA and protein levels of NLRP3 in an NF-κB-independent manner. Moreover, we reported for the first time that the inhibition of mTOR suppressed mitochondrial reactive oxygen species (ROS) production in BMDMs stimulated by an NLRP3 agonist. Furthermore, N-acetyl-L-cysteine, a ROS inhibitor, decreased NLRP3 expression, and rotenone, a robust ROS inducer, partially reversed the inhibitory effect of INK128 on NLRP3. These results demonstrated that mTOR regulated the activation of the NLRP3 inflammasome at least partially via ROS-induced NLRP3 expression. Importantly, in vivo data demonstrated that INK128 treatment prominently attenuated lupus nephritis and suppressed NLRP3 inflammasome activation in B6.MRL-FASlpr/J lupus mice. Taken together, our results suggest that activation of mTOR/ROS/NLRP3 signaling may contribute to the development of SLE.

Background/Aim: Women with advanced ovarian carcinoma are less likely to receive platinum-based chemotherapy and surgery due to a greater risk of cytotoxicity and poorer outcomes. We attempted to improve a promising therapy against ovarian cancer by using a combination of dihydroartemisinin (DHA) and curcumin (Cur). Methods: Human ovarian cancer SKOV3 cells were treated with DHA, Cur alone, or a combination of both. The viability of SKOV3 cells was measured by Cell Counting Kit-8 (CCK-8) and a colony formation assay. The cell cycle and apoptosis of SKOV3 cells were monitored by flow cytometry. The mRNA and protein expression levels of target genes were respectively examined by qRT-PCR and western blot. The biological effects of miR-124 on midkine (MK) were verified by a luciferase activity analysis. Results: Combined treatment of DHA and Cur synergistically decreased cell viability, arrested cell cycle, and promoted apoptosis in SKOV3 cells. Moreover, it significantly attenuated the expression of oncogene MK and synergistically upregulated the expression of miR-124. Furthermore, miR-124 was verified to bind directly to the 3ʹ-untranslated region of MK mRNA, resulting in mRNA degradation and reduced MK protein levels. The combination of DHA with Cur significantly inhibited tumor growth in xenograft nude mice without obvious toxicity. Conclusion: Co-treatment with DHA and Cur exhibited a synergistic anti-tumor effect on SKOV3 cells both in vitro and in vivo.

The increased death of macrophages has been considered as a pathogenic factor for systemic lupus erythematosus (SLE), and dysfunction of autophagy may contribute to improper cell death. However, the effect of autophagy on macrophage during the pathogenesis of SLE is still unclear. Here we found that the death rate and autophagy level of macrophages significantly increased in MRL/lpr lupus-prone mice. Activation of toll-like receptor 7 (TLR7) triggered macrophage death in an autophagy-dependent but caspase-independent way in vitro. Moreover, P62/SQSTM1 is thought to have an essential role in selective autophagy. We also demonstrated that P62/SQSTM1 was required for TLR7-induced autophagy, and knockdown of P62 suppressed R848-induced cell death and LC3II protein accumulation. As an important mediator for cell–cell communication, Notch signaling is responsible for cell-fate decisions. Our results showed that activation of TLR7 also upregulated the expression of Notch1, especially its downstream target gene Hairy and enhancer of split 1 (Hes-1) in macrophages. Of note, we found that Hes-1, as a transcriptional factor, controlled TLR7-induced autophagy by regulating P62 expression. Furthermore, to confirm the above results in vivo, TLR7 agonist imiquimod (IMQ)-induced lupus mouse model was prepared. Splenic macrophages from IMQ-treated mice exhibited increased autophagy and cell death as well as enhanced expressions of Notch1 and Hes-1. Our results indicate that Notch1-Hes-1 signaling controls TLR7-induced autophagic death of macrophage via regulation of P62 in mice with lupus.

If there is a medullary canal in the C1 pedicle, a 3.5- or 4.0-mm-diameter pedicle screw can be safely inserted into the atlas and C1 pedicle screw fixation can be performed without any impact on fixation stability and clinical efficacy, even if the C1 pedicle height is less than 4.0 mm.

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Background: The incidence of nasopharyngeal carcinoma is increasing gradually, but the pathogenesis is not completely clear. MicroRNA, a highly conserved endogenous noncoding small molecule RNA, plays an essential role in the regulation of gene expression and is a hotspot in cancer research worldwide. Objectives: Although previous studies have confirmed that the abnormal expression of microRNAs is closely related to the progression of nasopharyngeal carcinoma, the role of miRNA-331-3p in nasopharyngeal carcinoma has not been studied. The purpose of this study was to explore the role and mechanism of miRNA-331-3p in the progression of nasopharyngeal carcinoma. Materials and Methods: Real-time quantitative reverse transcription polymerase chain reaction was performed to detect the expression of miRNA-331-3p in nasopharyngeal carcinoma clinical samples and cell lines (CNE-1 and 5-8F cells). After overexpression of miRNA-331-3p in CNE-1 cells, cell proliferation was measured by Cell Counting Kit-8 assay, cell invasion was detected by Transwell assay, and apoptosis was tested by flow cytometry. In addition, the dual-luciferase reporter assay was used to identify the target gene of miRNA-331-3p and Western blotting was performed to measure the relative protein expression. Results: The expression of miRNA-331-3p in nasopharyngeal carcinoma clinical samples and cells was decreased significantly. Overexpression of miRNA-331-3p markedly inhibited the proliferation and invasion of CNE-1 cells and promoted cell apoptosis. Moreover, overexpression of miRNA-331-3p reduced the expression of target gene elF4B, leading to inhibition of the phosphorylation of Phosphoinositide 3-kinase (PI3K) and Serine/ threonine kinase (AKT). Conclusion: miRNA-331-3p inhibited cell proliferation and induced cell apoptosis in nasopharyngeal carcinoma by targeting elF4B gene and then blocked the PI3K-AKT signaling pathway. Significance: The role of miRNA-331-3p in the development of NPC and its mechanism provide new ideas for the treatment of nasopharyngeal carcinoma.