Pro-inflammatory and anti-inflammatory circulating cytokines and periprosthetic osteolysis

We investigated the circulating levels of the main cytokines involved in bone resorption (IL-1β, IL-6, TNF-α), prostaglandins (PGE2) and metalloproteases (MMP-1), as possible early markers of osteolysis, in the serum of eight patients with periprosthetic osteolysis and ten patients without osteolysis. All had received a cementless hip prosthesis (ABG-1). We also assessed the serum levels of IL-11 and TGF-β anti-inflammatory cytokines exerting protective effect on bone resorption. The mean serum levels of IL-1β, IL-6, TNF-α, TGF-β, MMP-1, and PGE2 in patients with periprosthetic osteolysis did not differ significantly from those of patients without osteolysis or from those of normal controls. IL-11 serum levels were not detectable at all in any of the patients, while they were detected within normal reference values in the control subjects (significant inverse correlation). We believe that circulating cytokines cannot be regarded as markers of osteolysis, a condition characterised by a local inflammation without systemic signs of inflammation. On the contrary, the undetectable levels of IL-11 in implanted patients could provide evidence for a lack of balance between pro- and anti-inflammatory cytokines in these patients

Biocompatibility and applications of carbon nanotubes in medical nanorobots

The set of nanoelectromechanical systems (NEMS) based on relative motion of carbon nanotubes walls is proposed for use in medical nanorobots. This set includes electromechanical nanothermometer, jet nanoengine, nanosyringe (the last can be used simultaneously as nanoprobe for individual biological molecules and drug nanodeliver). Principal schemes of these NEMS are considered. Operational characteristics of nanothermometer are analyzed. The possible methods of these NEMS actuation are considered. The present-day progress in nanotechnology techniques which are necessary for assembling of NEMS under consideration is discussed. Biocompatibility of carbon nanotubes is analyzed in connection with perspectives of their application in nanomedicine

Biocompatibility and applications of carbon nanotubes in medical nanorobots

The set of nanoelectromechanical systems (NEMS) based on relative motion of carbon nanotubes walls is proposed for use in medical nanorobots. This set includes electromechanical nanothermometer, jet nanoengine, nanosyringe (the last can be used simultaneously as nanoprobe for individual biological molecules and drug nanodeliver). Principal schemes of these NEMS are considered. Operational characteristics of nanothermometer are analyzed. The possible methods of these NEMS actuation are considered. The present-day progress in nanotechnology techniques which are necessary for assembling of NEMS under consideration is discussed. Biocompatibility of carbon nanotubes is analyzed in connection with perspectives of their application in nanomedicine

Inflammatory status and cartilage regenerative potential of synovial fibroblasts from patients with osteoarthritis and chondropathy.

OBJECTIVES: To evaluate the inflammatory status and the cartilage regenerative potential of pathological synovial fibroblasts from patients with osteoarthritis (OA) compared with non-inflamed synovium (NS)-derived cells from patients with chondropathy. METHODS: The inflammatory cell phenotype was investigated based on the constitutive and inducible surface expression and secretion of various effector molecules using flow cytometry or ELISA assays. The capacity of cells to produce cartilage-like extracellular matrix was assessed using acid Alcian blue staining and type II collagen immunostaining after treatment with transforming growth factor beta1 (TGF-beta1). RESULTS: OA and NS fibroblasts consistently expressed CD29, CD44, CD49e, CD54, CD90 and CD106. Expression of high-affinity receptors for IL-4, IL-15, CXCL8 and CXCL12 was also detected but only intracellularly. All types of fibroblasts spontaneously released abundant amounts of CXCL12, CCL2, IL-6 and tissue inhibitor of metalloproteinase 1, while the production of IL-11, TGF-beta1, matrix metalloproteinase 1 (MMP-1) and MMP-9 was detected at moderate levels. Several other secreted factors remained undetectable. No statistically significant differences were noted between the two groups of fibroblasts. Treatment with the proinflammatory cytokine tumour necrosis factor alpha (TNF-alpha) up-regulated the same set of surface and secreted molecules, including CD54, CD106, membrane IL-15, CCL2 and CCL5. Under TGF-beta1 treatment and adipogenic culture conditions, both OA and NS fibroblasts displayed chondrogenic and adipocytic activities that were reduced in OA compared with NS cells. CONCLUSIONS: OA synovial fibroblasts did not display a distinct activated inflammatory phenotype compared with NS cells. However, they did differ in their reduced ability to produce cartilage-like matrix. This difference may be an additional important factor contributing to OA pathogenesis

Is the epithelial barrier hypothesis the key to understanding the higher incidence and excess mortality during COVID-19 pandemic? The case of Northern Italy

The high incidence and increased mortality of COVID-19 make Italy among the most impacted countries by SARS-CoV-2 outbreak. In the beginning of the pandemic, Northern regions accounted for 40% of cases and 45% of deaths from COVID-19 in Italy. Several factors have been suggested to explain the higher incidence and excess mortality from COVID-19 in these regions. It is noticed that Northern Italian regions, and particularly the cities in Po Valley, are the areas with the highest air pollution due to commercial vehicle traffic, industry and a stagnant meteorological condition, with one of the highest levels in Italy and Europe of fine particulate matter 2.5 micron or smaller in size (PM2.5). PM2.5, the major environmental pollutant deriving mainly by factory and automobile exhaust emissions and coal combustion, increases the expression of angiotensin-converting enzyme 2, the epithelial cell entry receptor for SARS-CoV-2, and thus increase the susceptibility to this virus. The epithelial barrier hypothesis proposes that many diverse diseases may rise from the disruption of epithelial barrier of skin, respiratory tract and gastrointestinal system, including allergic diseases, metabolic and autoimmune diseases, and chronic neuropsychiatric conditions. There is evidence of a close correlation between air pollution and airway epithelial barrier dysfunction. Air pollution, causing lung epithelial barrier dysfunction, may contribute to local chronic inflammation, microbiome dysbiosis and impaired antiviral immune response against SARS-CoV-2, all of which contribute to the high incidence and excess mortality from COVID-19. In addition, air pollution and epithelial barrier dysfunction contribute also to the higher prevalence of several comorbidities of COVID-19, such as diabetes, chronic obstructive pulmonary disease and obesity, which have been identified as risk factors for mortality of COVID-19. In this article, on the basis of epidemiological and environmental monitoring data in Northern Italy, it is suggested that epithelial barrier hypothesis may help to understand the excess burden and mortality from COVID-19

Switching on microglia with electro-conductive multi walled carbon nanotubes

We explored the mechanisms underlying microglia cell-carbon nanotube interactions in order to investigate whether electrical properties of Carbon-Nanotubes (CNTs) could affect microglia brain cells function and phenotype. We analyzed the effects induced by highly electro-conductive Multi-Walled-Carbon-Nanotubes (a-MWCNTs), on microglia cells from rat brain cortex and compared the results with those obtained with as prepared not conductive MWCNTs (MWCNTs) and redox-active Double-Walled-Carbon-Nanotubes (DWCNTs). Cell viability and CNT capacity to stimulate the release of nitric oxide (NO), pro-inflammatory (IL-1b, TNF-a) and anti-inflammatory (IL-10, TGF-b1) cytokines and neurotrophic factors (mNGF) were assessed. Electro-conductive MWCNTs, besides not being cytotoxic, were shown to stimulate, at 24 h cell exposure, classical "M100 microglia activation phenotype, increasing significantly the release of the main pro-inflammatory cytokines. Conversely, after 48 h cell exposure, they induced the transition from classical "M100 to alternative "M200 microglia phenotype, supported by anti-inflammatory cytokines and neuroprotective factor mNGF release. The analysis of cell morphology change, by tubulin and CD-206 þ labelling showed that M2 phenotype was much more expressed at 48 h in cells exposed to a-MWCNTs than in untreated cells. Our data suggest that the intrinsic electrical properties of CNTs could be exploited to modulate microglia phenotype and function stimulating microglia anti-inflammatory potential

Evaluation of the efficacy of carbon nanotubes for delivering peptides into mitochondria

Mitochondrial (mt) diseases are devastating neurodegenerative pathologies due tomutations in nuclear or mt genes. Among mtDNA pathogenic mutations, more than one half have been identified in transfer RNA (tRNA) genes. These are responsible for a wide range of pathologies including myopathies, encephalopathies, cardiomyopathies and deafness for which no effective treatment is available at present. Therefore, new strategies to suppress their damaging effects are required to envisage therapeutic approaches for these diseases. Here we report data for carbon nanotube (CNT) derivatives showing that the conjugates bearing a specific peptide sequence are able to target the mitochondria in yeast and human monocyte cells while the control derivative without the peptide diffuses into the cytoplasm. Moreover the compounds do not affect cellular viability and cytotoxicity both in vitro and in vivo. Toxicity of the constructs is also assessed on the simple pluricellular model Caenorhabditis elegans

Lentigo maligna and lentigo maligna melanoma in vivo differentiation with dermoscopy and reflectance confocal microscopy. a retrospective, multicentre study

IntroductionDermoscopic predictors of lentigo maligna (LM) and lentigo maligna melanoma (LMM) have been recently reported, but these have not been reported in reflectance confocal microscopy (RCM). Objectives(i) To validate dermoscopic predictors for LM/LMM, (ii) to identify RCM patterns in LM and LMM, and (iii) correlations between dermoscopic and RCM features in LM and LMM. Materials and MethodsA retrospective, multicentre study of consecutive lesions with histologically proven LM or LMM subtypes of the head and face, with complete sets of dermoscopic and RCM images. ResultsA total of 180 lesions were included (n = 40 LMM). Previously reported differential dermoscopic features for LM subtypes were confirmed. Other features significantly associated with LMM diagnosis included irregular hyperpigmented areas, shiny white streaks, atypical vessels and light brown colour at dermoscopy and medusa head-like structures, dermal nests and nucleated cells within the papillae at RCM (p < 0.05). Correlations among LM lesions between dermoscopic and RCM features included brown to-grey dots and atypical cells (epidermis), grey colour and inflammation and obliterated follicles and medusa head-like structures. Among LMM lesions, significant correlations included obliterated follicles with folliculotropism, both irregular hyperpigmented areas and irregular blotches with widespread atypical cell distribution (epidermis), dermal nests and nucleated cells within the papillae (dermis). Irregular blotches were also associated with medusa head-like structures (dermal epidermal junction [DEJ]). ConclusionsDermoscopic and RCM features can assist in the in vivo identification of LM and LMM and many are correlated. RCM three-dimensional analysis of skin layers allows the identification of invasive components in the DEJ and dermis

Redox active Double Wall Carbon Nanotubes show intrinsic anti-proliferative effects and modulate autophagy in cancer cells

In Double-Walled-Carbon-Nanotubes (DWCNTs) the outer shell screens the inner one from the external environment. As a consequence, the electronic properties of the smaller tube are enhanced and DWCNTs have therefore been advocated for a number of uses. In their raw form theymay contain small metallic clusters, left over from the catalytic process, that can give them a redox activity characterized by redox potentials in the range of one hundred millivolts and able to affect biological systems. Indeed, we find that redox active raw-DWCNTs inhibit rat colorectal cancer cell proliferation by blocking cells in the G2 phase through ROS generation by tumor cells. We show that raw-DWCNTs could also modulate autophagy in tumor cells through induction of intracellular acidification. To the best of our knowledge, this is the first time that DWCNTs have been found to inhibit proliferation and modulate autophagy in cancer cells. Our work further supports previous studies that provided promising results on the possibility of future applications of Carbon Nanotubes (CNTs) in nanomedicine