Diana Lelli

CURCUMIN USE IN PULMONARY DISEASES: STATE OF THE ART AND FUTURE PERSPECTIVES

Curcumin (diferuloylmethane) is a yellow pigment present in the spice turmeric (Curcuma longa). It has been used for centuries in Ayurveda (Indian traditional medicine) for the treatment of several diseases. Over the last several decades, the therapeutic properties of curcumin have slowly been elucidated. It has been shown that curcumin has pleiotropic effects, regulating transcription factors (e.g., NF-kB), cytokines (e.g., IL6, TNF-alpha), adhesion molecules (e.g., ICAM-1), and enzymes (e.g., MMPs) that play a major role in inflammation and cancerogenesis. These effects may be relevant for several pulmonary diseases that are characterized by abnormal inflammatory responses, such as asthma or chronic obstructive pulmonary disease, acute respiratory distress syndrome, pulmonary fibrosis, and acute lung injury. Furthermore, some preliminary evidence suggests that curcumin may have a role in the treatment of lung cancer. The evidence for the use of curcumin in pulmonary disease is still sparse and has mostly been obtained using either in vitro or animal models. The most important issue with the use of curcumin in humans is its poor bioavailability, which makes it necessary to use adjuvants or curcumin nanoparticles or liposomes. The aim of this review is to summarize the available evidence on curcumins effectiveness in pulmonary diseases, including lung cancer, and to provide our perspective on future research with curcumin so as to improve its pharmacological effects, as well as provide additional evidence of curcumins efficacy in the treatment of pulmonary diseases.

Systematic review of telemonitoring in COPD: an update.

Telemedicine may support individual care plans in people with chronic obstructive pulmonary disease (COPD), potentially improving the clinical outcomes. To-date there is no clear evidence of benefit of telemedicine in this patients. The aim of this study is to provide an update on the effectiveness of telemedicine in reducing adverse clinical outcomes. We searched the Pubmed database for articles published between January 2005 and December 2014. We included only randomized controlled trials exclusively focused on patients with COPD and with a telemedicine intervention arm. Evaluated outcomes were number of exacerbations, ER visits, COPD hospitalizations, length of stay and death. We eventually included 12 randomized controlled trials. Most of them had a small sample size and was of poor quality, with a wide heterogeneity in the parameters and technologies used. Most studies reported a positive effect of telemonitoring on hospitalization for any cause, with risk reductions between 10% and 63%; however only three studies reached statistical significance. The same trend was observed for COPD-related hospital admission and ER visits. No significative effects of telemedicine was evidenced in reducing length of hospital stay, improving quality of life and reducing deaths. In conclusion, our study confirms that the available evidence on the effectiveness of telemedicine in COPD does not allow to draw definite conclusions; most evidence suggests a positive effect of telemonitoring on hospital admissions and ER visits. More trials with adequate sample size and with adequate consideration of background clinical services are needed to definitively establish its effectiveness.

Curcumin and treatment of melanoma: The potential role of microRNAs.

Melanoma is the most aggressive type of skin cancer and is characterized by poor prognosis in its advanced stages because treatments are poorly effective and burdened with severe adverse effects. MicroRNAs (miRNAs) are small non-coding RNAs that are implicated in several cellular processes; they are categorized as oncogenic and tumor suppressor miRNAs. Several miRNAs are implicated in the pathogenesis and progression of melanoma, such as the tumor suppressor miR-let7b that targets cyclin D and regulates cell cycle. Curcumin is a natural compound derived from Curcuma longa L. (turmeric) with anti-cancer properties, documented also in melanoma, and is well tolerated in humans. Pharmacological activity of curcumin is mediated by modulation of several pathways, such as JAK-2/STAT3, thus inhibiting melanoma cell migration and invasion and enhancing apoptosis of these cells. The low oral bioavailability of curcumin has led to the development of curcumin analogues, such as EF24, with greater anti-tumor efficacy and metabolic stability. Potential anti-cancer activity of curcumin and its analogues is also mediated by modulation of miRNAs such as miR21, that is implicated in cell cycle regulation and apoptosis through down-regulation of PTEN and PDCD4 proteins. Curcumin has a potential role in the treatment of melanoma, though further studies are necessary to explore its clinical efficacy.

Curcumin and Lung Cancer: the Role of microRNAs.

BACKGROUND Lung cancer is one of the most common types of cancer worldwide and is characterized by a poor prognosis, related to both late diagnosis and lack of effective treatments. In the last years, microRNAs (miRNAs) have been demonstrated to have an important role in tumor microenvironment and immune regulation. These RNAs can be categorized into tumor-suppressor genes, such as let-7 family and miR-34, and oncogenes such as miR-221 and miR-222. Curcumin is a bioactive polyphenol that is documented to have promising anticancer activity, and to be well tolerated in humans. METHODS The present review aims to gather available evidence on the involvement of mRNAs in the therapeutic effects of curcumin against lung cancer. RESULTS The anti-cancer properties of curcumin against lung cancer have been shown in both cellular and experimental models and are mediated by modulation of several molecular targets that regulate the expression of transcription factors, inflammatory cytokines, enzymes, growth factors, receptors, adhesion molecules, antiapoptotic proteins, and cell cycle proteins, leading to cell apoptosis, inhibition of cell proliferation and migration, and also chemo- and radio-sensitization of lung cancer cells. Recent studies have documented that pharmacological effects of curcumin in lung cancer are also mediated by modulation of several miRNAs, such as downregulation of oncogenic miR-21 and upregulation of oncosuppressive miR-192-5p and miR-215. CONCLUSION Further studies are necessary to explore this very promising field and the link between regulation of oncogenic and tumor-suppressive miRNAs and putative anti-cancer properties of curcumin.

Analysis of volatile organic compounds: an innovative approach to heart failure characterization in older patients

BACKGROUND Analysis of exhaled volatile organic compounds (VOCs) may be applied for diagnostic purposes in some chronic diseases, but there are no data on their role for discriminating people with congestive heart failure (CHF), particularly in older patients where natriuretic peptides have lower accuracy. We evaluated whether VOCs analysis can discriminate patients with or without CHF, stratify CHF severity and predict the response to therapy of decompensated CHF. METHODS AND RESULTS We recruited 89 subjects admitted to an acute care ward with acutely decompensated CHF, 117 healthy controls and 103 chronic obstructive pulmonary disease (COPD) controls. CHF patients performed echocardiography. VOCs were collected using the Pneumopipe® and analyzed with the BIONOTE electronic nose. Partial least square analysis was used to evaluate the discriminative capacity of VOCs. Accuracy in discrimination of CHF versus healthy and COPD controls was 81% and 69%, respectively; accuracy did not decrease in a sensitivity analysis excluding subjects younger than 65 and older than 80 years. In CHF patients VOCs pattern could predict with fair precision ejection fraction and systolic pulmonary arterial pressure, but not changes in weight due to therapy. CONCLUSIONS VOCs pattern is able to discriminate older CHF patients from healthy people and COPD patients and correlates with cardiac function markers.

Breath-Printing of Heart Failure in Elderly

Comorbidity represents a confounding factor in exhaled breath analysis, in particular with elderly population, which often shows both respiratory and heart diseases. Congestive heart failure (CHF) is the first cause of hospitalization and a primary cause of death and disability in the elderly population. CHF has important metabolic implications, thus exhaled VOCs analysis may support CHF severity assessment and CHF discrimination against controls. VOCs pattern in CHF has not been yet investigated so far, even if an increase in acetone and pentane has been observed. Here, breathprint based CHF diagnosis and severity classification have been studied. Moreover, studying an elderly population, Chronic Obstructive Pulmonary Disease (COPD) patients have been enrolled, being COPD an important comorbidity in aged population.

Hemoglobin Concentration Influences N‐Terminal Pro B‐Type Natriuretic Peptide Levels in Hospitalized Older Adults with and without Heart Failure

To investigate the relationship between hemoglobin and N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) concentration in hospitalized older adults with or without a diagnosis of heart failure (HF).