Osteoporosis and alzheimer pathology: Role of cellular stress response and hormetic redox signaling in aging and bone remodeling

Alzheimer’s disease (AD) and osteoporosis are multifactorial progressive degenerative disorders. Increasing evidence shows that osteoporosis and hip fracture are common complication observed in AD patients, although the mechanisms underlying this association remain poorly understood. Reactive oxygen species (ROS) are emerging as intracellular redox signaling molecules involved in the regulation of bone metabolism, including receptor activator of nuclear factor-κB ligand-dependent osteoclast differentiation, but they also have cytotoxic effects that include lipoperoxidation and oxidative damage to proteins and DNA. ROS generation, which is implicated in the regulation of cellular stress response mechanisms, is an integrated, highly regulated, process under control of redox sensitive genes coding for redox proteins called vitagenes. Vitagenes, encoding for proteins such as heat shock proteins (Hsps) Hsp32, Hsp70, the thioredoxin, and the sirtuin protein, represent a systems controlling a complex network of intracellular signaling pathways relevant to life span and involved in the preservation of cellular homeostasis under stress conditions. Consistently, nutritional anti-oxidants have demonstrated their neuroprotective potential through a hormetic-dependent activation of vitagenes. The biological relevance of dose–response affects those strategies pointing to the optimal dosing to patients in the treatment of numerous diseases. Thus, the heat shock response has become an important hormetic target for novel cytoprotective strategies focusing on the pharmacological development of compounds capable of modulating stress response mechanisms. Here we discuss possible signaling mechanisms involved in the activation of vitagenes which, relevant to bone remodeling and through enhancement of cellular stress resistance provide a rationale to limit the deleterious consequences associated to homeostasis disruption with consequent impact on the aging process

Inflammation and Peripheral Arterial Disease

Peripheral arterial disease (PAD) is an atherosclerotic disease closely associated with high morbidity and mortality in cardiac events. Inflammation is crucial in atherosclerosis both at triggering and in progression. Numerous inflammatory biomarkers (cytokines, matrix metalloproteinases (MMPs), selectin, intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) C-reactive protein (CRP), fibrinogen) have been measured in atherosclerotic diseases including PAD. This paper summarizes the data on the inflammatory biomarkers for PAD pathophysiology and highlights the most useful markers in monitoring PAD outcomes

Pathophysiology of Chronic Peripheral Ischemia: New Perspectives

Peripheral arterial disease (PAD) affects individuals particularly over 65 years old in the more advanced countries. Hemodynamic, inflammatory, and oxidative mechanisms interact in the pathophysiological scenario of this chronic arterial disease. We discuss the hemodynamic, muscle tissue, and oxidative stress (OxS) conditions related to chronic ischemia of the peripheral arteries. This review summarizes the results of evaluating both metabolic and oxidative markers, and also therapy to counteract OxS. In conclusion, we believe different pathways should be highlighted to discover new drugs to treat patients suffering from PAD

Interferon-gamma, tumor necrosis factor-alpha, and lipopolysaccharide promote chitotriosidase gene expression in human macrophages

Human chitotriosidase (Chit), a chitinolytic enzyme, is a member of the chitinase family. In human plasma, Chit activity has been proposed as a biochemical marker of macrophage activation in several lysosomal diseases. Recently we found that Chit activity is higher in patients affected by Plasmodium falciparum malaria infection, suggesting that Chit may reflect induction of an immunological response. To assess this hypothesis, we evaluated the CHIT1 mRNA levels in human monocytes/macrophages (HMMs) following treatment with interferon-gamma (IFNϒ), tumor necrosis factor-alpha (TNFα), and lipopolysaccharide (LPS). Stimulation of macrophages with INF-ϒ, TNF-α, and LPS resulted in an increase in Chit activity as well as the levels of CHIT1 mRNA as measured by quantitative real-time PCR. The data presented in this article show that Chit plays a role in the response to the activation of INF-ϒ-, TNF-α-, and LPS-driven macrophages, suggesting that the production of Chit by macrophages could have biological relevance in the immune-response

Data supporting the role of electric field and electrode material on the improvement of the ageing effects in hydrogenated amorphous silicon solar cells

Hydrogenated amorphous Si (a­Si:H) solar cells are strongly affected by the well known Staebler–Wronski effect. This is a worsening of solar cell performances under light soaking which results in a substantial loss of cell power conversion efficiency compared to time zero performance. It is believed not to be an extrinsic effect, but rather a basic phenomenon related to the nature of a­Si:H and to the stability and motion of H­related species in the a­Si:H lattice. This work has been designed in support of the research article entitled “Role of electric field and electrode material on the improvement of the ageing effects in hydrogenated amorphous silicon solar cells” in Solar Energy Materials & Solar Cells (Scuto et al. [1]), which discusses an electrical method based on reverse bias stress to improve the solar cell parameters, and in particular the effect of temperature, electric field intensity and illumination level as a function of the stress time. Here we provide a further set of the obtained experimental data results

Regression of bilateral orbital inflammation with anti-CD20 in a patient with relapsing granulomatosis with polyangiitis: A case report

To describe a case of bilateral orbital inflammation in a patient with relapsing granulomatosis with polyangiitis as only sign of disease recurrency treated with anti-CD20 antibodies

Measurements and Simulations on the Mechanisms of Efficiency Losses in HIT Solar Cells

We study the electrical and the optical behavior of HIT solar cell by means of measurements and optoelectrical simulations by TCAD simulations. We compare the HIT solar cell with a conventional crystalline silicon solar cell to identify the strengths and weaknesses of the HIT technology. Results highlight different mechanisms of electrical and optical efficiency losses caused by the presence of the amorphous silicon layer. The higher resistivity of the a-Si layers implies a smaller distance between the metal lines that causes a higher shadowing. The worst optical coupling between the amorphous silicon and the antireflective coating implies a slight increase of reflectivity around the 600 nm wavelength

Modulation of NLRP3 Inflammasome through Formyl Peptide Receptor 1 (Fpr-1) Pathway as a New Therapeutic Target in Bronchiolitis Obliterans Syndrome

Chronic rejection is the major leading cause of morbidity and mortality after lung transplantation. Bronchiolitis obliterans syndrome (BOS), a fibroproliferative disorder of the small airways, is the main manifestation of chronic lung allograft rejection. We investigated, using transgenic mice, the mechanisms through which the deficiency of IL-1β/IL-18, Casp-1, or Fpr-1 genes could be protective in an experimental model of BOS, induced in mice by allogeneic heterotopic tracheal transplantation. Fpr-1 KO mice showed a marked reduction in histological markers of BOS and of mast cell numbers compared to other groups. Molecular analyses indicated that the absence of the Fpr-1 gene was able to decrease NF-κB nuclear translocation and modulate NLRP3 inflammasome signaling and the mitogen-activated protein kinase (MAPK) pathway in a more significant way compared to other groups. Additionally, Fpr-1 gene deletion caused a reduction in resistance to the apoptosis, assessed by the TUNEL assay. Immunohistochemical analyses indicated changes in nitrotyrosine, PARP, VEGF, and TGF-β expression associated with the pathology, which were reduced in the absence of the Fpr1 gene more so than by the deletion of IL-1β/IL-18 and Casp-1. We underline the importance of the NLRP3 inflammasome and the pathogenic role of Fpr-1 in experimental models of BOS, which is the result of the modulation of immune cell recruitment together with the modulation of local cellular activation, suggesting this gene as a new target in the control of the pathologic features of BOS

Key Mechanisms and Potential Implications of <i>Hericium erinaceus</i> in NLRP3 Inflammasome Activation by Reactive Oxygen Species during Alzheimer’s Disease

Alzheimer’s disease (AD) is the principal cause of dementia, and its incidence increases with age. Altered antioxidant systems and inflammation have an important role in the etiology of neurodegenerative disorders. In this study, we evaluated the effects of Hericium erinaceus, a nutritional mushroom with important antioxidant effects, in a rat model of AD. Animals were injected with 70 mg/Kg of AlCl3 daily for 6 weeks, and Hericium erinaceus was administered daily by gavage. Before the experiment’s end date, behavioral test training was performed. At the end of the study, behavioral changes were assessed, and the animals were euthanized. Brain tissues were harvested for further analysis. AlCl3 mainly accumulates in the hippocampus, the principal region of the brain involved in memory functions and learning. Hericium erinaceus administration reduced behavioral changes and hippocampal neuronal degeneration. Additionally, it reduced phosphorylated Tau levels, aberrant APP overexpression, and β-amyloid accumulation. Moreover, Hericium erinaceus decreased the pro-oxidative and pro-inflammatory hippocampal alterations induced by AD. In particular, it reduced the activation of the NLRP3 inflammasome components, usually activated by increased oxidative stress during AD. Collectively, our results showed that Hericium erinaceus has protective effects on behavioral alteration and histological modification associated with AD due to the modulation of the oxidative and inflammatory pathways, as well as regulating cellular brain stress