Reduced expression of RanBPM Is associated with poorer survival from lung cancer and increased proliferation and invasion of lung cancer cells in vitro

Background/Aim: Ran binding protein microtubule-organizing centre (RanBPM), also known as RanBP9, is a scaffold protein conserved through evolution. We investigated the role of RanBPM in human lung cancer. Materials and Methods: Transcripts of RanBPM were determined in 56 human lung cancers along with paired normal lung tissues using real-time PCR. Association with prognosis was analyzed by online Kaplan–Meier survival analysis. In vitro lung cancer cell functional assays examined the impact of RanBPM-knockdown on cellular growth and invasion. Results: Higher expression of RanBPM was observed in tumor when compared to paired normal lung tissues. Increased RanBPM expression was seen in patients with longer overall and disease-free survival. Knockdown of RanBPM in lung cancer cell lines resulted in increased growth and invasion in vitro. Conclusion: Increased expression of RanBPM associates with postponed disease progression and better prognosis. RanBPM plays an inhibitory role in regulating proliferation and invasion of lung cancer cells

The molecular impact of pigment epithelium-derived factor, PEDF, on lung cancer cells and the clinical significance

Pigment epithelium-derived factor (PEDF) is an endogenous protein factor that has been shown to act as anti-angiognesis factor. The present study aimed to determine the direct biological effects of PEDF on lung cancer cells and deduce a clinical relevance in patients with lung cancer, major cause of death worldwide in which the knowledge of PEDF remains poor. We constructed a mammalian expression system for human PEDF produced recombinant PEDF (rhPEDF) protein from 3T3 cells. The expression of PEDF was examined using SDS-PAGE and Western blot analysis. Using the rhPEDF protein, we investigated the biological function of PEDF in the lung cancer cells as well as endothelial cells. PEDF expression levels were assessed in a cohort of human lung cancer specimen (77 pairs of matched normal and tumour tissues), in association with patient clinical variables and survival, using quantitative analysis of PEDF. In vitro, we found that administration of rhPEDF on two lung cancer cell lines (A549 and SK-MES1) significantly reduced tumour cell growth (P<0.05) with no significant effect on the growth of vascular cell line (HECV). We also found that rhPEDF significantly decreased lung cancer motility and adhesion to extracellular matrix (Matrigel) when compared with the control cells (P<0.05). We showed that reduced PEDF levels in lung cancer tissues significantly correlated with lymph node metastasis and an overall poor prognosis in the lung cancer patients. PEDF suppresses the growth and motility of lung cancer cells and has a significant correlation with the clinical outcome of the patients. These results contribute to our understanding of the molecular mechanisms of PEDF and indicates a potential prognostic and therapeutic impact of PEDF in lung cancer

The impact of Metastasis Suppressor-1, MTSS1, on oesophageal squamous cell carcinoma and its clinical significance

<p>Abstract</p> <p>Background</p> <p>Metastasis suppressor-1 (MTSS1) has been proposed to function as a cytoskeletal protein with a role in cancer metastasis. Recent studies have demonstrated the clinical significance of MTSS1 in certain type of cancers, yet the clinical relevance of MTSS1 in oesophageal squamous cell carcinoma (ESCC) has not been reported.</p> <p>Methods</p> <p>In this study, we assessed the expression levels of MTSS1 in tumours and its matched adjacent non-tumour tissues obtained from 105 ESCC patients. We also used ESCC cells with differing MTSS1 expression and assessed the influence of MTSS1 on ESCC cells.</p> <p>Results</p> <p>Down-regulation of MTSS1 expression was observed both in oesophageal tumour tissues and ESCC cancer cell lines. We also reported that MTSS1 expression was associated with tumour grade (p = 0.024), lymph node metastasis (p = 0.010) and overall survival (p = 0.035). Patients with high levels of MTSS1 transcripts had a favorable prognosis in comparison with those who had reduced or absent expression levels. Using over-expression and knockdown approach, we created sublines from ESCC cells and further demonstrated that MTSS1 expression in ESCC cells significantly influenced the aggressiveness of the oesophageal cancer cells, by reducing their cellular migration and in vitro invasiveness.</p> <p>Conclusion</p> <p>MTSS1 serves as a potential prognostic indicator in human ESCC and may be an important target for cancer therapy.</p

Short chain fatty acids potently induce latent HIV-1 in T-cells by activating P-TEFb and multiple histone modifications

AbstractHIV patients with severe periodontitis have high levels of residual virus in their saliva and plasma despite effective therapy (HAART). Multiple short chain fatty acids (SCFAs) from periodontal pathogens reactivate HIV-1 in both Jurkat and primary T-cell models of latency. SCFAs not only activate positive transcription elongation factor b (P-TEFb), which is an essential cellular cofactor for Tat, but can also reverse chromatin blocks by inducing histone modifications. SCFAs simultaneously increase histone acetylation by inhibiting class-1/2 histone deacetylases (HDACs) and decrease repressive histone tri-methylation at the proviral LTR by downregulating expression of the class-3 HDAC sirtuin-1 (SIRT1), and the histone methyltransferases enhancer of Zeste homolog 2 (EZH2) and suppressor of variegation 3–9 homolog 1 (SUV39H1). Our findings provide a mechanistic link between periodontal disease and enhanced HIV-1 replication, and suggest that treatment of periodontal disease, or blocking the activities of SCFAs, will have a therapeutic benefit for HIV patients

Ru doping induced spin frustration and enhancement of the room-temperature anomalous Hall effect in La2/3Sr1/3MnO3 films

In transition-metal-oxide heterostructures, the anomalous Hall effect (AHE) is a powerful tool for detecting the magnetic state and revealing intriguing interfacial magnetic orderings. However, achieving a larger AHE at room temperature in oxide heterostructures is still challenging due to the dilemma of mutually strong spin-orbit coupling and magnetic exchange interactions. Here, we exploit the Ru doping-enhanced AHE in LSMRO epitaxial films. As the B-site Ru doping level increases up to 20 percent, the anomalous Hall resistivity at room temperature can be enhanced from nOhmcm to uOhmcm scale. Ru doping leads to strong competition between ferromagnetic double-exchange interaction and antiferromagnetic super-exchange interaction. The resultant spin frustration and spin-glass state facilitate a strong skew-scattering process, thus significantly enhancing the extrinsic AHE. Our findings could pave a feasible approach for boosting the controllability and reliability of oxide-based spintronic devices

Super-tetragonal Sr4Al2O7: a versatile sacrificial layer for high-integrity freestanding oxide membranes

Releasing the epitaxial oxide heterostructures from substrate constraints leads to the emergence of various correlated electronic phases and paves the way for integrations with advanced semiconductor technologies. Identifying a suitable water-soluble sacrificial layer, compatible with the high-quality epitaxial growth of oxide heterostructures, is currently the key to the development of large-scale freestanding oxide membranes. In this study, we unveil the super-tetragonal Sr4Al2O7 (SAOT) as a promising water-soluble sacrificial layer. The distinct low-symmetric crystal structure of SAOT enables a superior capability to sustain epitaxial strain, thus allowing for broad tunability in lattice constants. The resultant structural coherency and defect-free interface in perovskite ABO3/SAOT heterostructures effectively restrain crack formations during the water-assisted release of freestanding oxide membranes. For a variety of non-ferroelectric oxide membranes, the crack-free areas can span up to a few millimeters in length scale. These compelling features, combined with the inherent high-water solubility, make SAOT a versatile and feasible sacrificial layer for producing high-quality freestanding oxide membranes, thereby boosting their potential for innovative oxide electronics and flexible device designs.Comment: 5 figures and SI, it is the second version of this manuscrip

Metagenomic Next-Generation Sequencing in the Diagnosis of HHV-1 Reactivation in a Critically Ill COVID-19 Patient: A Case Report

Background: Secondary infections pose tremendous challenges in Coronavirus disease 2019 (COVID-19) treatment and are associated with higher mortality rates. Clinicians face of the challenge of diagnosing viral infections because of low sensitivity of available laboratory tests. Case Presentation: A 66-year-old woman initially manifested fever and shortness of breath. She was diagnosed as critically ill with COVID-19 using quantitative reverse transcription PCR (RT-qPCR) and treated with antiviral therapy, ventilator and extracorporeal membrane oxygenation (ECMO). However, after the condition was relatively stabled for a few days, the patient deteriorated with fever, frequent cough, increased airway secretions, and increased exudative lesions in the lower right lung on chest X-rays, showing the possibility of a newly acquired infection, though sputum bacterial and fungal cultures and smears showed negative results. Using metagenomic next-generation sequencing (mNGS), we identified a reactivation of latent human herpes virus type 1 (HHV-1) in the respiratory tract, blood and gastrointestinal tract, resulting in a worsened clinical course in a critically ill COVID-19 patient on ECMO. Anti-HHV-1 therapy guided by these sequencing results effectively decreased HHV-1 levels, and improved the patient\u27s clinical condition. After 49 days on ECMO and 67 days on the ventilator, the 66-year-old patient recovered and was discharged. Conclusions: This case report demonstrates the potential value of mNGS for evidence-based treatment, and suggests that potential reactivation of latent viruses should be considered in critically ill COVID-19 patients

Whole-genome sequencing of <em>Oryza brachyantha</em> reveals mechanisms underlying <em>Oryza</em> genome evolution

The wild species of the genus Oryza contain a largely untapped reservoir of agronomically important genes for rice improvement. Here we report the 261-Mb de novo assembled genome sequence of Oryza brachyantha. Low activity of long-terminal repeat retrotransposons and massive internal deletions of ancient long-terminal repeat elements lead to the compact genome of Oryza brachyantha. We model 32,038 protein-coding genes in the Oryza brachyantha genome, of which only 70% are located in collinear positions in comparison with the rice genome. Analysing breakpoints of non-collinear genes suggests that double-strand break repair through non-homologous end joining has an important role in gene movement and erosion of collinearity in the Oryza genomes. Transition of euchromatin to heterochromatin in the rice genome is accompanied by segmental and tandem duplications, further expanded by transposable element insertions. The high-quality reference genome sequence of Oryza brachyantha provides an important resource for functional and evolutionary studies in the genus Oryza