The telomerase activator TA-65 protects from cigarette smoke-induced small airway remodeling in mice through extra-telomeric effects.

Small airway remodeling (SAR) is a key phenomenon of airflow obstruction in smokers, leading to chronic obstructive pulmonary disease (COPD). SAR results in an increased thickness of small airway walls, with a combination of peribronchiolar fibrosis with increased fibrous tissue and accumulation of mesenchymal and epithelial cells. SAR pathogenesis is still unclear but recent data suggest that alterations in telomerase activity could represent a possible underlying mechanism of SAR.

Lack of Transcription Factor p53 Exacerbates Elastase-Induced Emphysema in Mice.

The transcription factor p53 is overexpressed in the lung of patients with emphysema, but it remains unclear if it has a deleterious or protective effect in disease progression. We investigated the role of p53 in the elastase-induced emphysema model and the molecular underlining mechanisms. Wild-type (WT) and p53(-/-) mice were instilled with pancreatic porcine elastase.

The role of p53 in lung macrophages following exposure to a panel of manufactured nanomaterials.

Manufactured nanomaterials (MNMs) have the potential to improve everyday life as they can be utilised in numerous medical applications and day-to-day consumer products. However, this increased use has led to concerns about the potential environmental and human health impacts. The protein p53 is a key transcription factor implicated in cellular defence and reparative responses to various stress factors.

The cyclooxygenase-2-prostaglandin E2 pathway maintains senescence of chronic obstructive pulmonary disease fibroblasts.

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with lung fibroblast senescence, a process characterized by the irreversible loss of replicative capacity associated with the secretion of inflammatory mediators. However, the mechanisms of this phenomenon remain poorly defined.

Objectives: The aim of this study was to analyze the role of prostaglandin E2 (PGE2), a prostaglandin known to be increased in COPD lung fibroblasts, in inducing senescence and related inflammation in vitro in lung fibroblasts and in vivo in mice.

Longitudinal and noninvasive assessment of emphysema evolution in a murine model using proton MRI.

Ultrashort echo time (550 μs) MR imaging was implemented to track the emphysema development in mice lung challenged with elastase. Two parameters, namely, signal intensity and T 2, were used to monitor the disease evolution. Nine mice were imaged before and at 24 h as well as at 3 and 8 weeks after elastase instillation.

Blood glutathione decrease in subjects carrying lamin A/C gene mutations is an early marker of cardiac involvement.

Dominant inherited Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy type 1B are due to mutations in the LMNA gene encoding lamin A/C and present similar life-threatening cardiac disease, the early diagnosis of which lacks reliable biomarkers. Glutathione depletion characterizes subjects with cardiac diseases of non-genetic aetiology. We examined blood glutathione in 22 LMNA-mutated subjects without altered left ventricular ejection fraction (LVEF>40%) measured by conventional echocardiography.

Role of nitric oxide synthases in elastase-induced emphysema.

Nitric oxide (NO) in combination with superoxide produces peroxynitrites and induces protein nitration, which participates in a number of chronic degenerative diseases. NO is produced at high levels in the human emphysematous lung, but its role in this disease is unknown. The aim of this study was to determine whether the NO synthases contribute to the development of elastase-induced emphysema in mice.

Delayed cardiomyopathy in dystrophin deficient mdx mice relies on intrinsic glutathione resource.

Oxidative stress contributes to the pathogenesis of Duchenne muscular dystrophy (DMD). Although they have been a model for DMD, mdx mice exhibit slowly developing cardiomyopathy. We hypothesized that disease process was delayed owing to the development of an adaptive mechanism against oxidative stress, involving glutathione synthesis.

Glutathione deficiency in cardiac patients is related to the functional status and structural cardiac abnormalities.

Background: The tripeptide glutathione (L-gamma-glutamyl-cysteinyl-glycine) is essential to cell survival, and deficiency in cardiac and systemic glutathione relates to heart failure progression and cardiac remodelling in animal models. Accordingly, we investigated cardiac and blood glutathione levels in patients of different functional classes and with different structural heart diseases.

Methods: Glutathione was measured using standard enzymatic recycling method in venous blood samples obtained from 91 individuals, including 15 healthy volunteers and 76 patients of New York Heart Association (NYHA) functional class I to IV, undergoing cardiac surgery for coronary artery disease, aortic stenosis or terminal cardiomyopathy.

The cannabinoid receptor type 2 promotes cardiac myocyte and fibroblast survival and protects against ischemia/reperfusion-induced cardiomyopathy.

Post-myocardial infarction (MI) heart failure is a major public health problem in Western countries and results from ischemia/reperfusion (IR)-induced cell death, remodeling, and contractile dysfunction. Ex vivo studies have demonstrated the cardioprotective anti-inflammatory effect of the cannabinoid type 2 (CB2) receptor agonists within hours after IR. Herein, we evaluated the in vivo effect of CB2 receptors on IR-induced cell death, fibrosis, and cardiac dysfunction and investigated the target role of cardiac myocytes and fibroblasts.

Neutral sphingomyelinase inhibition participates to the benefits of N-acetylcysteine treatment in post-myocardial infarction failing heart rats.

Deficiency in cellular thiol tripeptide glutathione (L-gamma glutamyl-cysteinyl-glycine) determines the severity of several chronic and inflammatory human diseases that may be relieved by oral treatment with the glutathione precursor N-acetylcysteine (NAC). Here, we showed that the left ventricle (LV) of human failing heart was depleted in total glutathione by 54%. Similarly, 2-month post-myocardial infarction (MI) rats, with established chronic heart failure (CHF), displayed deficiency in LV glutathione.

A 42-year-old man with a densely vascular spinal mass.

A 42-year-old man was admitted to the neurosurgery department because of paraparesis and sensory deficits of both feet. A solitary exophytic lesion of the thoracic spine was seen on MRI, and angiography further revealed the presence of feeding and draining vessels and intra-lesional shunting. The preoperative diagnosis was spinal hemangioblastoma.

In vivo fusion of circulating fluorescent cells with dystrophin-deficient myofibers results in extensive sarcoplasmic fluorescence expression but limited dystrophin sarcolemmal expression.

To investigate the therapeutic potential of bone marrow transplantation in Duchenne muscular dystrophy, green fluorescent protein-positive (GFP+) bone marrow cells were transplanted into irradiated wild-type and dystrophin-deficient mdx mice. Tibialis anterior muscles showed fivefold to sixfold more GFP+ mononucleated cells and threefold to fourfold more GFP+ myofibers in mdx than in wild-type mice. In contrast, dystrophin expression in mdx mice remained within the level of nontransplanted mdx mice, and co-expression with GFP was rare.

Adult bone marrow-derived stem cells in muscle connective tissue and satellite cell niches.

Skeletal muscle includes satellite cells, which reside beneath the muscle fiber basal lamina and mainly represent committed myogenic precursor cells, and multipotent stem cells of unknown origin that are present in muscle connective tissue, express the stem cell markers Sca-1 and CD34, and can differentiate into different cell types. We tracked bone marrow (BM)-derived stem cells in both muscle connective tissue and satellite cell niches of irradiated mice transplanted with green fluorescent protein (GFP)-expressing BM cells. An increasing number of GFP+ mononucleated cells, located both inside and outside of the muscle fiber basal lamina, were observed 1, 3, and 6 months after transplantation.

Peptides derived from the onconeural HuD protein can elicit cytotoxic responses in HHD mouse and human.

Anti-Hu syndrome is a paraneoplastic neurologic disease seemingly associated with an efficient antitumoral immune response against HuD protein expressed by both small cell lung cancer (SCLC) and neurons. Since anti-Hu antibodies are not pathogenic, and oligoclonal CD8(+) T cells infiltrate neoplastic and nervous tissues, we examined MHC class I-restricted immunogenicity of human HuD. Among 14 HuD-derived peptides potentially immunogenic in HLA-A*0201 restriction, 10 had actual in vitro binding capacity to the HLA molecule, 8 elicited specific cytotoxic T lymphocytes (CTLs) in a humanized murine model after peptidic vaccination, 2 also elicited specific CTLs in healthy humans, and 1 was naturally processed and presented to the immune system.