Disordered tumor cell metabolism is involved in the process of tumorigenesis. Proline metabolism is of critical importance for tumor cells, and pyrroline-5-carboxylate reductase 1 (PYCR1), a key proline biosynthesis enzyme, has been reported to be overexpressed in prostate cancer and to promote tumor cell growth in breast cancer. The present study investigated the relationship between PYCR1 and non-small cell lung cancer (NSCLC). The results revealed that PYCR1 was overexpressed in NSCLC tumor tissues compared with adjacent normal tissues. High PYCR1 expression was associated with poor prognosis in patients with NSCLC. Following knockdown of PYCR1 by small interfering RNA, cell proliferation was revealed to be significantly inhibited and the cell cycle was arrested, while apoptosis was increased in SPC-A1 and H1703 NSCLC cells. Furthermore, the silencing of PYCR1 resulted in the downregulation of expression of the cell cycle regulator cyclin D1, the regulator of the mitochondrial apoptotic pathway B-cell lymphoma-2, and B-cell lymphoma-extra large. The results of the present study indicated the involvement of PYCR1 in the proliferation and apoptosis of NSCLC. Therefore, PYCR1 may be a novel therapeutic target for inhibiting cell proliferation in lung cancer.

This study revealed the importance of Dsg2 in suppression of NSCLC development and progression. Further studies will explore whether restoration of Dsg2 expression is a novel strategy in control of NSCLC.

Background: The kinesin family member C1 (KIFC1, also known as HSET) is a kinesin superfamily protein (KIFs). Although KIFC1 acts as a crucial role in the development of several human cancers, the KIFC1 expression profile and functional remain unclear in non-small cell lung cancer (NSCLC). Methods:We collected the fresh NSCLC samples and paired normal lung tissue in patients with lung cancer operation, and detected KIFC1 expression using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting. To expand on previous smaller-scale studies, NSCLC tissue microarrays (TMA) were analyzed by IHC. Finally, cell lines were employed to further probe the potential mechanisms, Results:In this study, we described that KIFC1 was significantly upregulated in NSCLC tissues compared with the corresponding normal tissues. Moreover, KIFC1 overexpression was associated with the poor overall survival (OS) of NSCLC patients, and siRNA-mediated knockdown of KIFC1 significantly suppressed tumor cell proliferation in vitro. Further verification showed that inhibition of KIFC1 gene expression caused the upregulation of the cyclin-dependent kinases inhibitor p21 and downregulation of the cell cycle driver protein cdc2, which arrested cells in the G2-M phase.Conclusions: we report that increased KIFC1 expression may promote cell proliferation and identified it as a biomarker of unfavorable prognosis in NSCLC patients.Keywords: Kinesin family member C1 (KIFC1); non-small cell lung cancer (NSCLC); cyclin-dependent kinase inhibitor 1A (p21); cell division cycle protein 2 homolog (cdc2); prognostic

Background: Extracellular mitochondrial DNA (mtDNA) was demonstrated to be capable of inducing pulmonary inflammation through TLR9 while its role in NLRP3 inflammation activation remains unknown.Methods: C57BL/6 mice were challenged intratracheally with mtDNA. Pulmonary pathology, the NLRP3 and caspase-1 p20 in lung tissues were assayed. PMA-primed THP-1 macrophages were incubated with mtDNA in vitro and cell-free medium were concentrated to detect caspase-1 p20 subunit and NLRP3 by Western blotting. Additionally, IL-1β, L-18, TNF-α and caspase-1 activity in culture were also analyzed by ELISA kits and activity assay kit. Results: Intratracheal administration of mtDNA increased NLRP3 and caspase-1 p20 subunit in lung together with excessive inflammation and damage. Inhibition of caspase-1 substantially diminished mtDNAinduced lung injury and inflammation. Exposed to mtDNA in THP-1 macrophages resulted in significant up-regulation of NLRP3 and increased caspase-1 p20 subunit release in culture. It also led to significant increased transcripts of NLRP3, ASC, caspase-1 and release of IL-1β, IL-18 and TNF-α in culture media. Futhermore, mtDNA exposure resulted in significant up-regulation of phosho -p38 MAPK and nucleus translocation of NF-κB. mtDNA-induced Transcripts of NLRP3 and ASC were inhibited by p38 siRNA inhibitor or NF-κB inhibitor. Conclusions: Extracellular mtDNA promote NLRP3 inflammasome activation, acute pulmonary inflammation and injury through TLR9, p38 MAPK and NF-κB pathways.

A network meta-analysis was conducted to compare the short-term efficacy and adverse events of different drugs for the treatment of postmenopausal osteoporosis (PMO), providing a more effective treatment for PMO. We initially searched through various databases like PubMed, Cochrane Library, and EMBASE from inception till October 2016. All randomized controlled trials (RCTs) of drugs for the treatment of PMO were included for direct and indirect comparison. A combination of direct and indirect evidence of different inhibitors of anti-diabetic drugs for treatment of PMO were considered for calculating the weighted mean difference (WMD) value or odd ratio (OR) value and to draw surface under the cumulative ranking (SUCRA) curves. Twenty-seven RCTs were ultimately incorporated into this network meta-analysis comprising of 48 200 patients suffering from PMO. The network meta-analysis revealed that compared with placebo, alendronate had better efficacy on improving bone mineral density (BMD) at lumbar spine, femoral neck, and total hip. Risedronate and raloxifene had relatively lower incidence of new vertebral fractures. The SUCRA analysis showed that alendronate had better efficacy on improving BMD, risedronate could significantly decrease the incidence of fresh fracture and bazedoxifene was relatively safe. The available evidence suggested that alendronate and risedronate might be the superior choices for the treatment of PMO, while bazedoxifene was a comparatively safer option for patients.

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Background: Protein regulator of cytokinesis-1 (PRC1) has been shown to participate in the completion of cytokinesis, and it is dysregulated in cancer processes. However, its relevance in lung squamous cell carcinoma (SCC) remained largely unknown. We aimed to study the expression pattern of PRC1 and assess its clinical significance in lung SCC.Methods: PRC1 protein expression in human lung SCC and adjacent normal lung tissues was detected by immunohistochemistry. PRC1 expression was assessed in association with clinicopathological features and clinical outcomes of lung SCC patients. Results: In lung SCC tissues, PRC1 protein expression was significantly higher than those in paired normal lung tissues. The lung SCC patients with PRC1 overexpression had an advanced pathological stage (TNM stage), positive lymph node metastasis, and a shorter overall survival (OS) time more frequently than patients with low PRC1 expression. Additional, PRC1 expression was also shown to be poor as a prognostic factor for OS in patients with lung SCC. Conclusions: Our study indicated that aberrant expression of PRC1 may point to biochemical recurrence in lung SCC. This highlights its potential as a valuable prognostic marker for lung SCC.

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