MiR-205-5p promotes lung cancer progression and is valuable for the diagnosis of lung cancer.

BACKGROUND: MicroRNAs (miRNAs) function as potential diagnostic biomarkers in various cancers. This study aimed to evaluate the roles of miR-205-5p in lung cancer progression and diagnosis. MATERIALS AND METHODS: MiR-205-5p was detected by quantitative real-time PCR. The effect of miR-205-5p on cell proliferation and metastasis was estimated by MTT and flow cytometry. The expression of TP53INP1 and related genes was analyzed by immunoblotting. The diagnostic value of miR-205-5p was analyzed using receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity. RESULTS: The miR-205-5p was increased in lung cancer tissues. MiR-205-5p mimics were promoted but its inhibitor suppressed cell proliferation and metastasis compared with control treatment in vitro and in vivo. By regulating the 3' untranslated region, miR-205-5p could negatively regulate TP53INP1 expression, which further inhibited the expression of RB1 and P21, but increased that of cyclinD1. Moreover, the serum miR-205-5p levels of patients with lung cancer were significantly higher than those of normal controls, and they were correlated with patients' gender, drinking status, and clinical stage. The area under the ROC curve of serum miR-205-5p in the diagnosis of non-small-cell lung cancer was 0.8250, respectively. The finding supported its possession of high diagnostic efficiency for lung cancer. CONCLUSIONS: MiR-205-5p promoted lung cancer cell proliferation and metastasis by negatively regulating the novel target TP53INP1, which further affected the expression of P21, RB1, and cyclin D1. Serum miR-205-5p is a novel and valuable biomarker for lung cancer diagnosis.

Delivery of miR-320a-3p by gold nanoparticles combined with photothermal therapy for directly targeting Sp1 in lung cancer.

Lung cancer is the second most common tumor and has the highest mortality rate. Both novel therapeutic targets and approaches are needed to improve the overall survival of patients with lung cancer. MicroRNA-320a-3p belongs to the miR-320a family and has been reported as a tumor suppressor in multiple cancers. However, its definitive role and precise mechanism in the progression of lung cancer remain unclear. In this study, we developed a new type of gold nanorod modified with polyethyleneimine that targets cancer-specific nanoparticles by RGD peptide, which could condense miRNA to self-assemble supramolecular nanoparticles. The designed nanoparticles can achieve integrin αvß3-targeted cancer therapy, realize photosensitive therapy by laser irradiation and attain gene-targeted therapy by miRNAs. These nanoparticles could deliver miR-320a into lung cancer cells specifically and efficiently. Moreover, we demonstrated that Au-RGD-miR-320a nanoparticles combined with laser irradiation dramatically inhibited the proliferation and metastasis, and enhanced the apoptosis of lung cancer, both in vitro and in vivo. In terms of the mechanism, miR-320a inhibits Sp1 expression by directly binding to the 3'UTR of Sp1, and it eventually enhanced the expression of PTEN and inhibited the expression of matrix metallopeptidase 9 (MMP9). These findings provide a new and promising anticancer strategy via the use of Au-RGD-miR-320a nanoparticles, and identify miR-320a/Sp1 as a potential target for future systemic therapy against lung cancer.

Remdesivir for severe covid-19: a clinical practice guideline.

CLINICAL QUESTION: What is the role of remdesivir in the treatment of severe covid-19? This guideline was triggered by the ACTT-1 trial published in the New England Journal of Medicine on 22 May 2020. CURRENT PRACTICE: Remdesivir has received worldwide attention as a potentially effective treatment for severe covid-19. After rapid market approval in the US, remdesivir is already being used in clinical practice. RECOMMENDATIONS: The guideline panel makes a weak recommendation for the use of remdesivir in severe covid-19 while recommending continuation of active enrolment of patients into ongoing randomised controlled trials examining remdesivir. HOW THIS GUIDELINE WAS CREATED: An international panel of patients, clinicians, and methodologists produced these recommendations in adherence with standards for trustworthy guidelines using the GRADE approach. The recommendations are based on a linked systematic review and network meta-analysis. The panel considered an individual patient perspective and allowed contextual factors (such as resources) to be taken into account for countries and healthcare systems. THE EVIDENCE: The linked systematic review (published 31 Jul 2020) identified two randomised trials with 1300 participants, showing low certainty evidence that remdesivir may be effective in reducing time to clinical improvement and may decrease mortality in patients with severe covid-19. Remdesivir probably has no important effect on need for invasive mechanical ventilation. Remdesivir may have little or no effect on hospital length of stay. UNDERSTANDING THE RECOMMENDATION: Most patients with severe covid-19 would likely choose treatment with remdesivir given the potential reduction in time to clinical improvement. However, given the low certainty evidence for critical outcomes and the fact that different perspectives, values, and preferences may alter decisions regarding remdesivir, the panel issued a weak recommendation with strong support for continued recruitment in randomised trials.

Evaluation of the TRPM protein family as potential biomarkers for various types of human cancer using public database analyses.

The Transient Receptor Potential Melastatin (TRPM) protein family members have been demonstrated to be involved in a variety of different types of human cancer. However, to the best of our knowledge, there has not yet been a systematic study regarding the mRNA expression of the TRPM protein family or its prognostic value in human cancer. The present study investigated TRPM expression and its prognostic value in various human cancer types via the Oncomine database, Kaplan-Meier plotter, and the PrognoScan and Gene Expression Profiling Interactive Analysis databases. It was revealed that the transcriptional levels of TRPM1, TRPM3 and TRPM6 were decreased in the majority of cancer tissues, while TRPM2 was increased in most cancer types. In addition, the high or low transcriptional levels of the TRPM protein family members were associated with survival outcomes of different types of solid tumors. The present study suggested that certain TRPM protein family members may serve as useful biomarkers for cancer prognosis and anticancer targets for cancer treatment.

Leptin enhances glycolysis via OPA1-mediated mitochondrial fusion to promote mesenchymal stem cell survival.

Transplantation of mesenchymal stem cells (MSCs) is emerging as a potential therapy for cardiovascular diseases. However, the poor survival of transplanted MSCs is a major obstacle to improving their clinical efficacy. Accumulating evidence indicates that hypoxic preconditioning (HPC) can improve the survival of MSCs. It has been previously reported that leptin plays a critical role in HPC­enhanced MSC survival through increasing optic atrophy 1 (OPA1)­dependent mitochondrial fusion. Survival of MSCs mainly relies on glycolysis as an energy source. The close relationship between leptin and glucose homeostasis has attracted intense scientific interest. Furthermore, emerging evidence indicates that mitochondrial dynamics (fusion and fission) are associated with alterations in glycolysis. The aim of the present study was to investigate whether leptin increases MSC survival through metabolic regulation. Leptin­modulated increased OPA1 expression was found to be associated with increased glycolysis. However, the glycolytic efficacy of leptin was abrogated after silencing OPA1 using a selective siRNA, suggesting that OPA1 directly regulates glycolysis. Furthermore, the activation of sodium­glucose symporter 1 (SGLT1) was markedly induced by leptin. However, leptin­induced glycolysis was primarily blocked by SGLT1 inhibitor treatment. Thus, leptin regulates OPA1­dependent glycolysis to improve MSC survival primarily through SGLT1 activation. We therefore identified a pivotal leptin/OPA1/SGLT1 signaling pathway for mitochondrial dynamic­mediated glycolysis, which may optimize the therapeutic efficiency of MSCs.

Contribution of IVIM to Conventional Dynamic Contrast-Enhanced and Diffusion-Weighted MRI in Differentiating Benign from Malignant Breast Masses.

BACKGROUND: The aim of this study was to determine whether the indicators obtained from intravoxel incoherent motion (IVIM) imaging can improve the characterization of benign and malignant breast masses compared with conventional dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted magnetic resonance imaging (DW-MRI). PATIENTS AND METHODS: This study included 23 benign and 31 malignant breast masses of 48 patients. Main indicators were initial enhancement ratio (IER), time-signal intensity curve (TIC), apparent diffusion coefficient (ADC), tissue diffusivity (D), pseudodiffusivity (D*), and perfusion fraction (f). The discriminative abilities of the different models were compared by means of receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) analysis. RESULTS: D had the highest AUC (0.980), sensitivity (93.55%), specificity (100%), and diagnostic accuracy (96.36%). Both D and TIC could provide the independent predicted features for malignant breast masses. The combination of D and TIC had an AUC of up to 0.990. CONCLUSION: D of IVIM can effectively complement existing conventional DCE-MRI and DW-MRI in differentiating malignant from benign breast masses. IVIM combined with DCE-MRI is a robust means of evaluating breast masses.