The number of patients with chronic obstructive pulmonary disease (COPD) has been rising with continued exposure to environmental risk factors and aging of populations around the world. Frailty is a geriatric syndrome with a decline in physiological reserve and often coexists with chronic diseases such as COPD. Frailty is an independent risk factor for the development and progression of COPD, and COPD can lead to frailty; treating one might improve the other. Thus, there is an increasing interest in the assessment of frailty in patients with COPD. Furthermore, early identification and assessment of frailty in patients with COPD may affect the choice of intervention and improve its effectiveness. Based on the current literature, the intent of this review was to summarize and discuss frailty assessment tools used for COPD patients and the relevant clinical practices for predicting outcomes. We ascertain that using suitable frailty assessment tools could facilitate physicians to screen and stratify physically frail patients with COPD. Screening appropriately targeted population can achieve better intervention outcomes and pulmonary rehabilitation among frail COPD patients.

Background: To elucidate whether rapamycin, the inhibitor of mTOR (mammalian target of rapamycin), can potentiate the cytotoxic effect of docetaxel in lung cancer cells and to probe the mechanism underlying such enhancement. Methods: Lung cancer cells were treated with docetaxel and rapamycin. The effect on the proliferation of lung cancer cells was evaluated using the MTT method, and cell apoptosis was measured by flow cytometry. Protein expression and level of phosphorylation were assayed using Western Blot method. Results: Co-treatment of rapamycin and docetaxel was found to favorably enhance the cytotoxic effect of docetaxel in four lung cancer cell lines. This tumoricidal boost is associated with a reduction in the expression and phosphorylation levels of Survivin and ERK1/2, respectively. Conclusion: The combined application of mTOR inhibitor and docetaxel led to a greater degree of cancer cell killing than that by either compound used alone. Therefore, this combination warrants further investigation in its suitability of serving as a novel therapeutic scheme for treating advanced and recurrent lung cancer patients.

To investigate the effect of miR-188-5p overexpression on the invasion and migration of cultured lung cancer cells, and on related cellular mechanisms that underlie epithelial mesenchymal transition (EMT). Human lung cancer cell line 95D was transfected with miR-188-5p mimic. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to quantify the expression levels of genes including E-cadherin, Snail, α-SMA, and MGAT3. Changes in cell motility, invasion and proliferation were studied using scratch migration assay, transwell invasion assay, and colony formation assay, respectively. The expression levels of EMT-related proteins and MGAT3 protein were also determined via immunofluorescent staining. The ability of miR-188-5p to regulate its target gene, MGAT3, was assessed using dual luciferase activity assay. Lung cancer cell line 95D showed the lowest miR-188-5p expression level thus was used in this study. Transfection with miR-188-5p mimic significantly suppressed migration, invasion and clonal formation potency of 95D cells. Dual luciferase activity assay implicated that miR-188-5p exerts its negative regulatory effect on MGAT3 expression through recognizing the 3′ untranslated region (3′UTR) of the MGAT3 gene. Over-expression of miR-188-5p in 95D cells also remarkably increased E-cadherin protein expression and decreased the expression levels of Snail and α-SMA, which suppressed the EMT process. MiR-188-5p reduces the expression of MGAT3 and inhibits the metastatic properties of a highly invasive lung cancer cell line, probably via targeted regulation of EMT process. Further research to explore the potential therapeutic value of miR-188-5p, both as a biomarker and as a drug candidate for the management of metastatic lung cancer may be warranted.

Background: The aim of this study was to evaluate the function of RhoGDI2 in lung cancer epithelial-mesenchymal transition (EMT) process and to illustrate the underlying mechanisms that will lead to improvement of lung cancer treatment. Methods: The RhoGDI2 knock-down and overexpressing A549 cell lines were first constructed. The influence of RhoGDI2 on cytoskeleton in A549 cells was studied using two approaches: G-LISA-based Rac1 activity measurement and immunostaining-based F-actin distribution. The expression levels of key EMT genes were analyzed using real time quantitative polymerase chain reaction (RT-qPCR), western blot and immunostaining in untreated and RhoGDI2 knock-down or overexpressing A549 cells in both in vivo and in vitro experimental settings. Results: Our study showed that the activity of Rac1, a key gene that is crucial for the initiation and metastasis of human lung adenocarcinoma, causing the redistribution of F-actin with partial loss of cell-cell adhesions and stress fibers, was significantly suppressed by RhoGDI2. RhoGDI2 promoted the expression of EMT marker gene E-cadherin and repressed EMT promoting genes Slug, Snail, α-SMA in both A549 cells and lung and liver organs derived from the mouse models. Knocking-down RhoGDI2 induced abnormal morphology for lung organs. Conclusion: These findings indicate that RhoGDI2 repressed the activity of Rac1 and may be involved in the rearrangement of cytoskeleton in lung cancer cells. RhoGDI2 suppresses the metastasis of lung cancer mediated through EMT by regulating the expression of key genes such as E-cadherin, Slug, Snail and α-SMA in both in vivo and in vitro models.

As life expectancy increases, frailty and cognitive impairment have become major factors influencing healthy aging in elderly individuals. Frailty is a complicated clinical condition characterized by decreased physiological reserve and multisystem abnormalities. Cognitive frailty is a subtype of frailty that has aroused widespread concern among the scientific community and public health organizations. We herein review the pathogenesis of cognitive frailty, such as chronic inflammatory response, immunological hypofunction, imbalanced oxidative stress, reduced regenerative function, endocrine dysfunction, and energy metabolism disorder. Although existing interventions show some therapeutic effects, they do not meet the current clinical needs. To date, studies using stem cell technology for treating age-related diseases have achieved remarkable success. This suggests the possibility of applying stem cell treatment to cognitive frailty. We analyzed stem cell-based strategies for targeting anti-inflammation, antioxidation, regeneration, and immunoregulation using mesenchymal stem cells, as well as potential therapeutic targets for cognitive frailty. Based on this investigation, we propose a highly effective and low-cost stem cell-based replacement strategy. However, there is a lack of comprehensive research on the prospect of stem cell transplantation for improving cognitive frailty. In this review, we aim to provide the scientific background and a theoretical basis for testing cell therapy in future research.

With the acceleration of global aging, frailty syndrome has become an important public health challenge. This article reviews the new perspective of the microbiome-gut-brain axis (MGBA) in the pathogenesis and intervention strategies of frailty, and systematically analyzes the bidirectional association between the gut microbiome and frailty, the potential biological mechanisms, and the therapeutic progress targeting the microbiome. Evidence shows that microbiome-gut-brain axis (MGBA) plays a pivotal role in frailty, and its regulation not only helps to reveal the multidimensional nature of frailty, but also provides important directions for the development of novel biomarkers and personalized interventions. Multi-dimensional targeting of MGBA may be an effective way to promote healthy aging.