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Bone tissue engineering is a field to manufacture scaffolds for bone defects that cannot repair without medical interventions. Ceramic nanoparticles such as bredigite have importance roles in bone regeneration. We synthesized a novel strontium (Sr) doped bredigite (Bre) nanoparticles (BreSr) and then developed new nanocomposite scaffolds using polycaprolactone (PCL), poly lactic acid (PLA) by the 3D-printing technique. Novel functional nanoparticles were synthesized and characterized using field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), and energy dispersive spectroscopy (EDS: map). The nanoparticles were uniformly distributed in the polymer matrix composites. The 3D- printed scaffolds were investigated using scanning electron microscopy (SEM), X-ray diffraction (XRD), attenuated total reflection-fourier transform infrared (ATR-FTIR), degradation rate porosity, mechanical tests, apatite formation and cell culture. Degradation rate and mechanical strength were increased in the PLA/PCL/Bre-5%Sr nanocopmposite scaffolds. Hydroxyapatite crystals were also created on the scaffold surface in the bioactivity test. The scaffolds supported viability and proliferation of human osteoblasts. Gene expression and calcium deposition in the samples containing nanoparticles indicated statistical different than the scaffolds without nanoparticles. The nanocomposite scaffolds were implanted into the critical-sized calvarial defects in rat for 3 months. The scaffolds containing Bre-Sr ceramic nanoparticles exhibited the best potential to regenerate bone tissue.

The potential toxic effects of short chrysotile and amphibole asbestos fibers with lengths5 to ∼10 µm have been debated over the years. This stems from the large database of epidemiology, toxicology, and

Holton and colleagues have performed a risk assessment after measuring asbestos released from several samples of facial makeup. Unfortunately, it is not possible to interpret or generalize their findings because the authors have not described the source(s) of the talc tested or the asbestos concentrations of the samples. The concentration of amphiboles varies widely between sources, and the authors are urged to divulge the locations of the ore bodies providing the talc for their samples, as well as the asbestos concentration of the samples, so that the results may be interpreted and possibly generalized.

This study characterizes airborne asbestos exposures resulting from the adult application of cosmetic talc body powders spiked with known concentrations of tremolite. Raw talc ores were spiked with 0.005% and 0.1% asbestiform or non-asbestiform tremolite. Personal samples were collected during 16 simulated events, including puff and shaker application and associated clean-up activities. Airborne fiber levels (PCM) were not significantly different for simulations involving talc spiked with asbestiform and non-asbestiform tremolite (

Carcinogenic properties of particulates depend, among other factors, on dimensional characteristics that affect their ability to reach sensitive tissue, to be removed or retained, and to interact with the cells.To model mesothelioma and lung cancer potency of amphibole particles based on their dimensional characteristics and mineral habit (asbestiform vs. nonasbestiform) utilizing epidemiological data and detailed size information.The datasets from recently created depository of dimensional information of elongate mineral particles were used to correlate mesothelioma and lung cancer potency with the fraction of particles in a specific size range and the ratio of length and width in different powers. In addition, the cancer potency factors were estimated and compared for 30 asbestiform, 15 nonasbestiform, and 10 mixed datasets.For particles longer than 5 µm, the highest correlation with mesothelioma potency was achieved for width0.22 µm, and with lung cancer0.28 µm. The statistical power of the correlation was observed to lose significance at a maximum width of 0.6-0.7 µm. Mesothelioma potency correlated with length in the power of 1.9 divided by width in the power of 2.97, lung cancer potency with length in the power of 0.4 divided by width in the power of 1.17. The predicted cancer potencies of asbestiform, nonasbestiform, and mixed categories were significantly different.While additional studies in this direction are warranted, this paper should serve as an additional confirmation for the role of fiber dimensions in the carcinogenicity of amphibole elongate mineral particles (EMPs).

Background/Aims: The fluoro-edenite fibrous amphibole was identified as an environmental pollutant associate to risk of carcinogenicity. In Sicily (Italy), it represents a public health issue because fluoro-edenite fibers are present in the soil of Biancavilla, a town located on the south-west slopes of the volcano Etna. Since the relationship between exposure to fluoro-edenite and the onset of lung disorders have been documented, in vitro studies were performed to clarify the mechanisms of damage, but most aspects remain unknown. Here, we focus on the effects of mineral fibers in a primary culture of lung fibroblasts. We supposed that the cells react to fluoro-edenite exposure by establishing a process of adaption that could modify their metabolic activity, their proliferation, and their physiological functions, as the production of extracellular matrix (ECM) components. Methods: To verify our hypothesis, we used immunofluorescence, cell proliferation, senescence, apoptosis, scratch, Western blot, Reverse transcription-polymerase chain reaction (RT-PCR), and evaluation of extracellular matrix components assays. Results: Results demonstrated that lung fibroblasts react to fluoro-edenite by a down-regulation of mitochondrial activity, a reduction of cell growth and migration, and a resistance to apoptosis. These elements suggested the induction of a premature senescent phenotype that was confirmed by senescence-associated beta-galactosidase (SA-β-Gal) activity, and by the analysis of ECM elements. We found an unbalance of collagens ratio, and changes in matrix metalloproteinase3 production and release. Conclusion: Our data suggest that fluoro-edenite-induced senescence of lung fibroblasts could be an early and underestimated step that may drive fibroblasts toward a fibrotic and carcinogenic phenotype.

In Calabria (Southern Italy) naturally occurring asbestos (NOA) mainly occurs in the ophiolitic sequences cropping in the Mount Reventino area. The most common type of asbestos detected was the amphibole tremolite; fibrous antigorite and minor chrysotile were also found. The development of asbestos-related diseases depends on, among other things, the morphological characteristics of fibers, length and width, affecting the durability of asbestos fibers in the lung. In this work fifteen lung samples of sheep, goats and wild boars, grazing around the Mount Reventino area were collected and asbestos fibers analysed. Observed fibers (357), of which 97 % were tremolite and 3 % antigorite fibers, were grouped according to species, grazing area and age of the animals. The aim of this work was to highlight any differences among the groupings and to compare our size results with data in literature related to exposed populations. Principal Component Analysis (PCA) highlighted a positive correlation between tremolite fiber length and width and revealed groupings in terms of animal age. The Kruskal-Wallis test showed statistically significant differences between fiber mean widths in young and old animals. 63 % observed asbestiform fibers were longer than 5 μm and 7 % of the fibers were longer than 20 μm (critical fiber length connected to the frustrated phagocytosis by the macrophage). Fibers conforming to the Stanton Hypothesis size (predictor of the carcinogenic potency of fibers) were 1 %. Our size parameters of fibers detected in the animal lungs were in fairly good agreement with literature data for human asbestos exposure to tremolite. These results confirmed that an animal-sentinel system could be used to monitor the natural background of the airborne breathable fibers exposure. In addition, the size correlation of animal-human breathed fibers could be useful to study their potential toxicity. Additional data are necessary for improving the agreement with human exposure data.

Asbestos ore was sampled from a historical anthophyllite mine in Staten Island, New York. High-resolution transmission electron microscopy (HRTEM) was used to image the structure of nineteen fibers of the anthophyllite asbestos. The anthophyllite was characterized by a high level of chain width disorder, involving wide chain multiplicity faults (CMFs) that were frequent in fibers, randomly spaced, and ranged from one to eight chains in width. This chain width disorder was manifest by streaking of electron diffraction rows of chain width. The anthophyllite asbestos fibers were found to be produced by longitudinal splitting rather than crystal growth. Such splitting is a function of cleavage along CMFs rather than crystal boundaries. The morphology of the fibers is consistent with anthophyllite asbestos mined in Finland associated with lung cancer and mesothelioma. These findings may have regulatory implications.

Introduction: Asbestos, the most frequent cause of occupational cancer, continues to be consumed on a massive scale, with millions of people exposed on a daily basis. This review explains why we have failed in curtailing the silent epidemic of asbestos-related disease and why the numbers of asbestos victims are likely to remain high. Emerging and developed countries have to be reminded that asbestos exposure has yet to become a problem of the past. The worldwide spread of asbestos, followed by the surge of asbestos-related cancers, resembles the lung cancer epidemic caused by smoking and stimulated by manufacturers.Areas covered: Underreporting of malignant mesothelioma and asbestos-induced lung cancer, frequently-used arguments in the amphibole/chrysotile debate and the conclusion from bona-fide research organizations, that all forms of asbestos are carcinogenic, are reviewed. Special attention is paid to the consequences of ubiquitous environmental asbestos and the 'changing face' of malignant mesothelioma in countries with heavy asbestos use in the past.Expert opinion: Experts in oncology, respiratory medicine, occupational and public health, and basic researchers must take responsibility and acknowledge the ongoing silent epidemic of asbestos-related diseases. The call for a world-wide asbestos ban is more urgent than ever.

The onset of malignant mesothelioma (MM) is linked to exposure to asbestos fibers. Asbestos fibers are classified as serpentine (chrysotile) or amphibole, which includes the crocidolite, amosite, anthophyllite, tremolite, and actinolite types. Although few studies have been undertaken, anthophyllite has been shown to be associated with mesothelioma, and tremolite, a contaminant in talc and chrysotile, is a risk factor for carcinogenicity. Here, after characterizing the length and width of these fibers by scanning electron microscopy, we explored the cytotoxicity induced by tremolite and anthophyllite in cells from an immortalized human mesothelial cell line (MeT5A), murine macrophages (RAW264.7), and in a rat model. Tremolite and short anthophyllite fibers were phagocytosed and localized to vacuoles, whereas the long anthophyllite fibers were caught on the pseudopod of the MeT5A and Raw 264.7 cells, according to transmission electron microscopy. The results from a 2‐day time‐lapse study revealed that tremolite was engulfed and damaged the MeT5A and RAW264.7 cells, but anthophyllite was not cytotoxic to these cells. Intraperitoneal injection of tremolite in rats induced diffuse serosal thickening, whereas anthophyllite formed focal fibrosis and granulomas on peritoneal serosal surfaces. Furthermore, the loss of Cdkn2a/2b, which are the most frequently lost foci in human MM, were observed in 8 cases of rat MM (homozygous deletion [5/8] and loss of heterozygosity [3/8]) by array‐based comparative genomic hybridization techniques. These results indicate that tremolite initiates mesothelial injury and persistently frustrates phagocytes, causing subsequent peritoneal fibrosis and MM. The possible mechanisms of carcinogenicity based on fiber diameter/length are discussed., MeT5A (immortalized mesothelial cells) and RAW264.7 (macrophage lineage cells) were damaged by tremolite but not anthophyllite. Tremolite induced diffuse peritoneal thickening, whereas anthophyllite induced focal fibrosis. Furthermore, tremolite‐induced malignant mesothelioma frequently lost Cdkn2a/2b.

Tremolite–actinolite (TA) fibers from the lungs of deceased former Quebec mine workers were found to be coated with sub-nanometer particles. Qualitative chemical analyses were performed on the particles indicating that they were composed of silicon and oxygen. The crystal lattice structure of all amphibole minerals, including the TA series, is arranged as pairs of linear chains of SiO4 tetrahedra that are linked together to form double chains. Our observations of the TA fibers from miner’s lungs, made using a high-resolution transmission electron microscope, indicated that the tetrahedral silica chains were progressively split, forming dispersed sub-nanometer particles. The non-tetrahedral sites were removed at the surface of the TA fibers, presumably by the oxidation process involved in attempted phagocytosis, which also resulted in fragmentation of the tetrahedral chains. It was found that the silicon-rich particles (SRPs) were variable in diameter, consistent with fragments formed from the splitting of the tetrahedral chains. The TA fibers from lungs displayed coatings and linear interior zones of SRP parallel to the planes of longitudinal fiber splitting. The literature on very small nanoparticles is consistent with deep penetration of SRP into cell DNA interiors, oxidative stress, and carcinogenesis.

Two cases with diagnosis of mesothelioma were referred to our laboratories with a request for tissue burden analysis in order to determine the presence of ferruginous bodies and uncoated elongated mineral particles in tissue samples. The individuals shared in common a past background of working in tile manufacturing facilities where industrial talc was used in the production of the products. Both were found to have ferruginous bodies in their lung tissues as well as elongated talc fibers/ribbons and elevated numbers of noncommercial amphiboles in their tissues. To our knowledge, this is the first report of tissue assessment for the presence of elongated mineral particles in individuals whose exposures to talc occurred were while working in the manufacture of tile products and who developed the fiber-related cancer - mesothelioma.

Amphibole asbestos is related to lung fibrosis and several types of lung tumors. The disease-triggering mechanisms still challenge our diagnostic capabilities and are still far from being fully understood. The literature focuses primarily on the role and formation of asbestos bodies in lung tissues, but there is a distinct lack of studies on amphibole particles that have been internalized by alveolar epithelial cells (AECs). These internalized particles may directly interact with the cell nucleus and the organelles, exerting a synergistic action with asbestos bodies (AB) from a different location. Here we document the near-atomic- to nano-scale transformations induced by, and taking place within, AECs of three distinct amphiboles (anthophyllite, grunerite, “amosite”) with different Fe-content and morphologic features. We show that: (i) an Fe-rich layer is formed on the internalized particles, (ii) particle grain boundaries are transformed abiotically by the internal chemical environment of AECs and/or by a biologically induced mineralization mechanism, (iii) the Fe-rich material produced on the particle surface does not contain large amounts of P, in stark contrast to extracellular ABs, and (iv) the iron in the Fe-rich layer is derived from the particle itself. Internalized particles and ABs follow two distinct formation mechanisms reaching different physicochemical end-states.

Objective: What are the levels of asbestos exposure that cause each type of health effect? The objective of this study was to review the available scientific evidence on exposure levels for asbestos and their relationship to health effects. Method: An umbrella review of English-language reviews and meta-analyses, from 1980 to March 2021 was conducted. We included reviews involving quantified asbestos exposures and health outcomes. The review has been adapted to the indications of the PRISMA declaration. Methodological quality of the selected studies was assessed using the AMSTAR instrument. Results: We retrieved 196 references. After applying the search strategy and quality analysis, 10 reviews were selected for in-depth analysis. For lung cancer, the highest risk was observed with exposure to amphiboles. Longer, thinner fibers had the greatest capacity to cause lung cancer, especially those > 10 μm in length. For mesothelioma, longer and thinner fibers were also more pathogenic; amphiboles ≥ 5 μm are especially associated with increased mesothelioma risk. No studies observed an increased risk for lung cancer or mesothelioma at asbestos exposure levels 10μm. Para el mesotelioma, las fibras más largas y delgadas también fueron más patógenas; los anfíboles ≥ 5μm se asociaron con un mayor riesgo de mesotelioma. Ningún estudio observó mayor riesgo de cáncer de pulmón o de mesotelioma con niveles de exposición al asbesto

This work reviews the bio-chemical mechanisms leading to adverse effects produced when mineral fibres are inhaled and transported in the lungs from the perspective of a mineralogist. The behaviour of three known carcinogenic mineral fibres (crocidolite, chrysotile, and fibrous-asbestiform erionite) during their journey through the upper respiratory tract, the deep respiratory tract and the pleural cavity is discussed. These three fibres have been selected as they are the most socially and economically relevant mineral fibres representative of the classes of chain silicates (amphiboles), layer silicates (serpentine), and framework silicates (zeolites), respectively. Comparison of the behaviour of these fibres is made according to their specific crystal-chemical assemblages and properties. Known biological and subsequent pathologic effects which lead and contribute to carcinogenesis are critically reviewed under the mineralogical perspective and in relation to recent progress in this multidisciplinary field of research. Special attention is given to the understanding of the cause-effect relationships for lung cancer and malignant mesothelioma. Comparison with interstitial pulmonary fibrosis, or "asbestosis", will also be made here. This overview highlights open issues, data gaps, and conflicts in the literature for these topics, especially as regards relative potencies of the three mineral fibres under consideration for lung cancer and mesothelioma. Finally, an attempt is made to identify future research lines suitable for a general comprehensive model of the carcinogenicity of mineral fibres.

Vermiculite ore from Libby, Montana contains on average 24% of a mixture of toxic and carcinogenic amphibole asbestiform fibers. These comprise primarily winchite (84%), with smaller quantities of richterite (11%) and tremolite (6%), which are together referred to as Libby amphibole (LA).A total of 1883 individuals who were occupationally and/or environmentally exposed to LA and were diagnosed with asbestos-related pleuropulmonary disease (ARPPD) following participation in communitywide screening programs supported by the Agency for Toxic Substances and Disease Registry (ATSDR) and followed up at the Center for Asbestos Related Disease (CARD) between 2000 and 2010. There were 203 deaths of patients with sufficient records and radiographs. Best clinical and radiologic evidence was used to determine the cause of death, which was compared with death certificates.Asbestos-related mortality was 55% (n = 112) in this series of 203 patients. Of the 203 deaths, 34 (17%) were from asbestos-related malignancy, 75 (37%) were from parenchymal asbestosis, often with pleural fibrosis, and 3 (1.5%) were from respiratory failure secondary to pleural thickening.Asbestos is the leading cause of mortality following both occupational and nonoccupational exposure to LA in those with asbestos-related disease.

Exposure to Libby amphibole (LA) asbestos-like fibers is associated with increased risk of asbestosis, mesothelioma, pulmonary disease, and systemic autoimmune disease. LGM2605 is a small molecule antioxidant and free radical scavenger, with anti-inflammatory effects in various disease models. The current study aimed to determine whether the protective effects of LGM2605 persist during the late inflammatory phase post-LA exposure. Male and female C57BL/6 mice were administered daily LGM2605 (100 mg/kg) via gel cups for 3 days before and 14 days after a 200 µg LA given via intraperitoneal (i.p.) injection. Control mice were given unsupplemented gel cups and an equivalent dose of i.p. saline. On day 14 post-LA treatment, peritoneal lavage was assessed for immune cell influx, cytokine concentrations, oxidative stress biomarkers, and immunoglobulins. During the late inflammatory phase post-LA exposure, we noted an alteration in trafficking of both innate and adaptive immune cells, increased pro-inflammatory cytokine concentrations, induction of immunoglobulin isotype switching, and increased oxidized guanine species. LGM2605 countered these changes similarly among male and female mice, ameliorating late inflammation and altering immune responses in late post-LA exposure. These data support possible efficacy of LGM2605 in the prolonged treatment of LA-associated disease and other inflammatory conditions.

Comprehending heavy mineral composition of the sandy land in Northeast China (NESL) is of great significance for interpreting generation, pathways, source and geochemistry of sediments in this area. To this end, the fine-grained (μm) aeolian-fluvial sediments and loess deposits, which were taken from the Onqin Daga Sandy Land, the Horqin Sandy Land, the Hulun Buir Sandy Land and the Songnen Sandy Land, and from the downwind loess section (L1), respectively, were analyzed to construct the heavy mineral data set of NESL source and sink and to evaluate feasibility of the heavy mineral method in tracing the source of aeolian dust in Northeast China. Additionally, the

Biodurability is one of the main determinants of asbestos hazardousness for human health. Very little is known about the actual persistence of asbestos in lungs and its clearance, nor about differences in this regard between the different mineralogical types of asbestos. The aim of the present study was to evaluate the amount, the dimensional characteristics and the mineralogic kinds of asbestos in lungs (measured using SEM-EDS) of a series of 72 deceased subjects who were certainly exposed to asbestos (mainly crocidolite and chrysotile) during their life. Moreover, we investigated possible correlations between the lung burden of asbestos (in general and considering each asbestos type), as well as their dimension (length, width, and l/w ratio) and the duration of exposure, the latency- in case of malignant mesothelioma (MM), the survival and the time since the end of exposure. In 62.5% of subjects, asbestos burden in lungs was lower that the threshold considered demonstrative for occupational exposure. In 29.1% of cases no asbestos was found. Chrysotile was practically not detected. The mean length of asbestos fibers and the length to width ratio were significantly related to the duration of exposure to asbestos. No other statistically significant correlations were found between the amount and dimensional characteristics of asbestos (nor with the relative amount of each asbestos type) and the other chronological variables considered. In conclusion, it was pointed out that chrysotile can be completely removed from human lungs in

The Serine and Arginine-Rich Splicing Factor 1 (SRSF1) has a proto-oncogenic function, being associated with angiogenesis and frequently overexpressed in many human malignant neoplasms. Its immunohistochemical expression has never been investigated in malignant pleural mesothelioma (MPM). We evaluated SRSF1 immunoexpression and its possible relation to angiogenesis in a selected cohort of 10 fluoro-edenite(FE)-induced MPM cases. Methods: Immunohistochemical analyses with an anti-SRSF1 antibody were performed. We interpreted the cases as positive if tumor cell nuclei were stained, a semi-quantitative analysis of the cases was performed by evaluating the intensity of staining and the percentage of tumor positive cells. A microvessel density (MVD) count was also performed. Results: High and low immunoexpressions of SRSF1 were seen in six and four MPMs, respectively. A trend of shorter overall survival was found in FE-induced MPM patients with SRSF1 overexpression. In addition, a significant association between high-MVD and high SRSF1 immunoexpression (p = 0.0476) was found. Conclusions: SRSF1 appears to be involved in MPM pathogenesis and its immunoexpression may represent a prognostic biomarker capable of identifying subgroups of patients with different prognosis. However, given the preliminary nature of the present study, further investigations on larger series, and additional in vitro studies, are required to validate our findings.

Background: The relationship between pleural plaques and cumulative asbestos exposure is controversial. Objectives: To evaluate the relationship between lung asbestos bodies (AB) and fibres (AF) and plaques presence and extension. Methods: In a necropsy series of shipyard workers with asbestos-related diseases, we measured counts (per g of dry lung tissue) of AB (thousands) and AF>1 μm (millions). Pleural plaques were classified into three extension grades. We fitted univariate and multivariable linear (dependent variables: AB and AF, log10 transformed) and multinomial (dependent variable: plaques grade) regression models. Results: We analysed 124 subjects, 13 without plaques 20 with grade 1, 69 with grade 2, and 22 with grade 3 plaques. Geometric means (GM) of AB were 10.6, 23.3, 126, and 140 in the four groups respectively (P=0.0001). GMs for AF (mostly amphiboles) were 1.2, 1.4, 7.3, and 12.9 (P=0.0001). AB and AF were strongly correlated (r=0.81). The likelihood of no plaques and grade 1 plaques decreased with increasing AB and AF doses, with a corresponding increase of grade 2 and 3 plaques. Plaque presence and extension was also associated with histologically verified asbestosis (P

Background Lung cancer screening with low‐dose computed tomography (CT) scanning (LDCT) is accepted as a screening tool, but its application to populations exposed to recognized occupational or environmental carcinogens is limited. We apply LDCT to a population with a predominantly nonoccupational exposure to a recognized human lung carcinogen, Libby amphibole asbestos (LA). Methods Patients in an asbestos disease clinic in Libby, Montana who were aged 50 to 84 years, greater than or equal to 20 pack‐year history of tobacco use (irrespective of quit date), and asbestos‐related pleuropulmonary disease on high‐resolution CT scan were offered free annual lung cancer screening over a 39‐month period. Results Of 2897 clinic patients, 1149 (39.7%) met eligibility criteria, and 567 (49%) were screened with 1014 low‐dose CT scans. Most screened patients had principally environmental (333 or 59%) or household exposure (145 or 25%) to LA. Seventeen primary lung cancers were identified, mostly in early stages: 10 at stage 1, two at stage 2, three at stages 3 to 4, and two at limited small‐cell cancers. The screening yield was 1.9 at baseline scan and 1.5% on the first annual scan. Conclusions Consistent with the guidelines of the National Comprehensive Cancer Network and American Association of Thoracic Surgery, LDCT for early lung cancer detection should be offered to people with significant exposure to occupational or environmental human lung carcinogens.

OBJECTIVE To evaluate the frequency and severity of pleuropulmonary alterations in anthophyllite-exposed former workers in Itapira, Sao Paulo, Brazil. The amphibole anthophyllite, a magnesium-iron silicate, had its mining, marketing, and use forbidden in Brazil in 1995. METHODS Former workers were followed from 1999 to 2011. All completed chest X-ray interpreted using the International Labour Office (ILO) classification. High-resolution computed tomography was used at the final evaluation. Spirometry assessed forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and FEV1/FVC throughout the follow-up period. Samples from the mined ore were analyzed by X-ray diffraction (XRD) and scanning electron microscopy coupled to energy dispersive spectroscopy (SEM-EDS). RESULTS XRD and SEM-EDS confirmed the presence in ore of anthophyllite at a concentration of 75%, in addition to tremolite and other amphiboles in lower concentrations. Twenty-eight subjects were evaluated. Median time of exposure was 3 years (minimum = 1; maximum = 18; interquartile interval = 1-4). Twenty cases of pleural abnormalities were diagnosed in 26 evaluated (77%). The average latency time was 25.6 ± 7.4 years. Two individuals (7.7%) showed progressive worsening of diffuse pleural thickening (DPT) and exhibited an annual FVC decrease of 85 mL and 150 mL, respectively. CONCLUSION This small sample showed a very high index of nonmalignant pleural abnormalities in anthophyllite-exposed workers compared with workers exposed to other kinds of fibers. Rapidly progressive DPT, defined by the severity of pleural compromise, was possibly secondary to the presence of other amphibole types in the inhaled dust. No significant loss of FVC was found in the studied group as a whole. No cases of asbestosis, lung carcinoma, and mesothelioma were diagnosed in this cohort.

Context: The potency of various mineral fiber types to produce mesothelioma was previously evaluated for numerous cohorts, but the differences in potencies for distinct fiber types have yet to be e...

BACKGROUND Temporal trends and broad geographical distributions of asbestos use and the incidence of malignant mesothelioma (MM) in the US still need to be studied. METHODS Data on asbestos consumption and production between 1900 and 2015 and MM mortality and incidence rates between 1975 and 2015 in the US were examined. Spatial distributions of MM mortality and incidence rates and their association with climate zone were analyzed. RESULTS Decline of MM incidence and mortality rates in the US occurred about 20 years after the peak of asbestos consumption-production in 1973. There are apparent north-south (N-S) gradients in MM mortality and incidence rates in the US. CONCLUSION Recent decline of MM incidence and mortality rates in the US may be associated with reduced US asbestos consumption. N-S MM gradients between 1999 and 2015 were likely related to larger asbestos requirements in building materials in the northern states.

This paper presents a geologic and mineralogical investigation of asbestiform amphibole from blueschist in the Diablo Range, northern California. The analysis of fibers in air samples shows that the dominant blueschist amphibole composition ranges from glaucophane to subordinate winchite. In outcrop, blueschist amphibole exhibits a velvety luster, and its occurrence ranges from crosscutting veins to highly deformed foliated and lineated tectonites. TEM and SEM photographs reveal a highly fibrous habit typically associated with asbestiform amphiboles. Dimensional analysis reveals a mean fiber width of 0.27 μm, and lengths and aspect ratios are shorter than reported for commercially exploitable asbestos, with a mean length of 2.8 μm and mean aspect ratio of 11.5. The data are consistent with other research showing that the width population of fibers, and not length or aspect ratio, is the key indicator of the asbestiform habit. The blueschist data are compared to non-asbestiform hornblende amphibole in granitic rocks. The fiber concentration of the hornblende (458 MFG) is low compared to the blueschist amphibole (107,880 MFG) and chrysotile in serpentinite (196,066 MFG), indicating that under similar conditions, the exposure potential from cleaved particles could be several orders of magnitude lower than from asbestiform particles. The asbestiform habit of glaucophane is present at two other locations in the Franciscan Complex, suggesting that asbestiform blueschist amphibole may be characteristic within blueschist terranes, and rock formations containing asbestiform amphibole may be more common and widespread than previously assumed.

In this study by considering the advantages of bredigite (Br) and titanium dioxide (TiO2) bioceramics, composite scaffolds of bredigite/titanium dioxide were prepared by the gelcasting method, then, to improve the mechanical, biological and antibacterial properties, scaffolds were coated with chitosan (Ch) polymer phase. The phase structure, fundamental groups, chemical composition, and elemental distribution analysis, morphology and the form of porosity were respectively characterized by XRD, FTIR, EDS, and SEM. Mechanical properties and porosity percentage of scaffolds were also measured by the compressive strength test and Archimedean method, respectively. In order to verify the cell compatibility, MG63 bone marrow cells were cultured on the surface of the specimens. The results showed that the addition of titanium dioxide to the scaffold of bredigite resulted in decrease of porosity and increase of compressive strength of scaffolds from 0.299 to 0.687 MPa. Furthermore, the coated scaffold with chitosan polymer reduced porosity from 83 to 63 percent and a remarkable improvement in compressive strength from 0.585 to 2.339 MPa. The results of the antibacterial test showed that in composite scaffolds, The diameter of the inhibition zone is 22 and 29 mm, in the culture media of Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive), respectively. On the other hand, the results of cell compatibility and cell adhesion tests showed that the scaffolds had no toxicity and the growth, proliferation, and adhesion of MG63 bone cells adjacent to the scaffolds was desirable. Therefore, the scaffold in this study can be used as an ideal scaffold for use in bone tissue engineering.

Literature evidence has demonstrated a high incidence of asbestos-related malignant pleural mesothelioma (MPM) in a Sicilian town (Biancavilla, Italy), where fluoro-edenite (FE) fibers were discovered some decades ago. As ATG7 immunohistochemical analysis has been ascribed as a prognostic tool of improved survival, we decided to investigate, in MPM patients, exposed and not exposed to FE fibers, the immunohistochemical expression of this autophagy-related protein named ATG7. We analyzed the correlation between ATG7 immunohistochemical level and clinicopathological parameters. Twenty MPM tissue samples, from patients with available clinical and follow-up data, were included in paraffin and processed for immunohistochemistry. The immunohistochemical results confirmed activation of the autophagic process in MPM. Densitometric and morphometric expressions of ATG7 were significantly increased in MPMs when compared to the control tissues. A significant association of a high level of ATG7 with increased survival was demonstrated, with a mean overall survival (OS) of 12.5 months for patients with high expression vs. a mean OS of 4.5 months for patients with low ATG7 expression. In addition, a significant correlation between ATG7 expression and the survival time of MPM patients was observed. This study represents a starting point to hypothesize the prognostic role of ATG7 which could be a reliable prognostic indicator in MPM.

Occupational chrysotile asbestos exposure data in Zimbabwe is limited. The aim of this study was therefore to develop a job exposure matrix (JEM) specific to the chrysotile asbestos cement manufacturing industry using the available personal exposure concentration data. Quantitative personal exposure chrysotile fibre concentration data collected by the two factories from 1996 to 2020 were used to construct the JEM. Exposure groups from which data was extracted were classified based on the Zimbabwe Standard Classification of Occupations (ZSCO), 2009–2019. Analysis of amphiboles in raw chrysotile was done by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). Descriptive statistics, namely mean, standard deviation and range were computed for the main variable, job/occupation. All jobs/occupations in both factories had annual mean personal exposure concentrations exceeding the OEL of 0.1 f/mL, except for the period from 2009 to 2016 in the Harare factory and the period from 2009 to 2020 in the Bulawayo factory. Despite the Harare factory having no AC manufacturing activity since 2017, personal exposure concentrations showed elevated levels for the period 2018–2020. Amphiboles were detected in almost all bulk samples of chrysotile asbestos analysed. The established JEM, which has been generated from actual local quantitative exposure measurements, can be used in evaluating historical exposure to chrysotile asbestos fibre, to better understand and predict occurrence of ARDs in future.

Human exposures to asbestiform elongate mineral particles (EMP) may lead to diffuse fibrosis, lung cancer, malignant mesothelioma and autoimmune diseases. Cleavage fragments (CF) are chemically identical to asbestiform varieties (or habits) of the parent mineral, but no consensus exists on whether to treat them as asbestos from toxicological and regulatory standpoints. Alveolar macrophages (AM) are the first responders to inhaled particulates, participating in clearance and activating other resident and recruited immunocompetent cells, impacting the long-term outcomes. In this study we address how EMP of asbestiform versus non-asbestiform habit affect AM responses. Max Planck Institute (MPI) cells, a non-transformed mouse line that has an AM phenotype and genotype, were treated with mass-, surface area- (s.a.), and particle number- (p.n.) equivalent concentrations of respirable asbestiform and non-asbestiform riebeckite/tremolite EMP for 24 h. Cytotoxicity, cytokines secretion and transcriptional changes were evaluated. At the equal mass, asbestiform EMP were more cytotoxic, however EMP of both habits induced similar LDH leakage and decrease in viability at s.a. and p.n. equivalent doses. DNA damage assessment and cell cycle analysis revealed differences in the modes of cell death between asbestos and respective CF. There was an increase in chemokines, but not pro-inflammatory cytokines after all EMP treatments. Principal component analysis of the cytokine secretion showed close clustering for the s.a. and p.n. equivalent treatments. There were mineral- and habit-specific patterns of gene expression dysregulation at s.a. equivalent doses. Our study reveals the critical nature of EMP morphometric parameters for exposure assessment and dosing approaches used in toxicity studies.

Worldwide studies have been published on the mortality of workers employed in asbestos-based materials for the production of clutches and brakes. However no one of these studies is related to Italian cases. Furthermore, not even surveys have been conducted in Italy to characterize the correlation between asbestos exposures and the possible occurring of asbestos-related disease. Our objectives are the following: i) to assess and quantify the asbestos exposure cases, ii) to describe the nature and the frequency of asbestos-related diseases among blue collar employees of an important factory producing brakes and clutches with chrysotile asbestos content from 1971 to 1993 and iii) to provide preliminary data on cumulative asbestos exposure estimated using lung fibre burden analysis. Critical appraisal of airborne asbestos fibre measurements and identification of cases of asbestos-related diseases between the blue collar employees, either notified to the local health authority or recovered from the Italian national Mesothelioma registry was investigated. Lung fibre burden analysis using the lung tissue samples from two deceased blue collar employees was also performed. Airborne asbestos fibre measurements (carried out in 1982) suggested asbestos fibres average concentrations of about 0.3 f/ml, while all 1992 measurements showed results below 0.1 f/ml. Furthermore, since 1988, we identified four cases of pleural plaques, three cases of asbestosis and seven cases of lung cancer. No case of malignant mesothelioma was found. In both lung cancer cases, analysed to measure the lung fibre burden, commercial amphiboles were absent or in limited concentration but chrysotile and, especially, tremolite asbestos were present in noticeable amount. In conclusion, since 1971 and up to early 1980s, exposure to chrysotile asbestos and talc, likely contaminated by tremolite, had been significant and comparable to levels causing asbestosis long-term risk. No case of malignant mesothelioma was found, that is consistent with the absence of amphiboles and with the lower risk of mesothelioma associated with the chrysotile asbestos. However a subset of the blue collar employees, the ones employed later on, could still have not reached the full risk condition, and so being still at risk of developing malignant mesothelioma. In the two lung cancer cases studied, the lung fibre burden was essentially made of chrysotile and tremolite. Lastly, lung cancer occurrence in the population of blue collar employees has been likely underestimated and the correct determination of lung cancer risk should be done through the mortality analysis of this population.Nella letteratura scientifica sono presenti studi epidemiologici di mortalità su coorti di lavoratori addetti alla produzione di materiali di attrito in amianto ma non in Italia, dove neppure sono disponibili indagini conoscitive per caratterizzare l’esposizione ad amianto e la possibile presenza di patologie asbesto-correlate. Per questa ragione si è ricostruita la natura e l’entità dell’esposizione ad amianto, la frequenza e la tipologia delle patologie asbesto-correlate in lavoratori di una importante industria di materiali di attrito in asbesto crisotilo utilizzato dal 1971 al 1993; si sono inoltre forniti iniziali elementi per una stima dell’esposizione cumulativa ad asbesto dei lavoratori attraverso l’analisi del carico polmonare di fibre di amianto. Si è operata una valutazione dei monitoraggi ambientali e una rilevazione dei casi di patologie asbesto-correlate diagnosticati tra lavoratori della fabbrica, oltre all’analisi di campioni di tessuto polmonare di due lavoratori per la determinazione del carico residuo di fibre di amianto. Monitoraggi ambientali eseguiti nel 1982 indicavano concentrazioni medie di 0,3 fibre/cc e nel 1992 inferiori a 0,1 fibre/cc per tutti i campioni. Dal 1988 sono stati osservati 4 casi di placche pleuriche, 3 casi di asbestosi, 7 casi di tumore polmonare, nessun caso di mesotelioma maligno. In ambedue i casi di tumore polmonare con analisi delle fibre di amianto gli anfiboli erano assenti o con valori modesti mentre per il crisotilo e soprattutto per la tremolite le concentrazioni rilevate erano consistenti. In conclusione, dagli anni ’70 ai primi anni ’80 l’esposizione ad amianto crisotilo e a talco, in parte contaminati da tremolite, è risultata consistente e compatibile con casi di asbestosi. Non sono stati osservati casi di mesotelioma maligno. Non essendo stati usati anfiboli questo può essere dovuto al più basso rischio di mesotelioma associato al crisotilo, ma parte dei lavoratori assunti in anni successivi potrebbero non essere ancora a pieno rischio. Il carico polmonare di fibre nei due casi di tumore polmonare è essenzialmente dato dal crisotilo e dalla tremolite. La frequenza di tumori polmonari incidenti in questa coorte è verosimilmente sottostimata; il rischio di questa neoplasia dovrebbe essere valutato attraverso uno studio della mortalità della coorte.

The interactions between six anthocyans (cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, malvidin-3-O-glucoside, cyanidin-3-O-rutinoside, delphinidin-3-O-rutinoside, malvidin-3-O-rutinoside) and cyclodextrins were investigated by means of computational techniques. Four different structures of the aforementioned anthocyans were considered, as a result of the dependence structure – pH value (flavylium cations in acidic medium, hemiketals in neutral solutions and two tautomeric quinones in alkaline environment). The results outlined that the anthocyanidin-3-O-rutinoside are favored for the obtaining of inclusion complexes with the cyclodextrins, mostly due to the larger number of OH groups involved in the formation of hydrogen bonds. For all the four types of structures, best results have been obtained for β- and γ-cyclodextrins.

International audience; Introduction: Asbestos-related diseases and cancers represent a major public health concern.Objective: To conduct a systematic review and meta-analysis to demonstrate that asbestos exposure increases the risk of prostate cancer.Methods: The PubMed, Cochrane Library, Embase, and ScienceDirect databases were searched using the keywords (prostate cancer OR prostatic neoplasm) AND (asbestos* OR crocidolite* OR chrysotile* OR amphibole* OR amosite*). To be included, articles needed to describe our primary outcome: Risk of prostate cancer after any asbestos exposure.Results: We included 33 studies with 15,687 cases of prostate cancer among 723,566 individuals. Asbestos exposure increased the risk of prostate cancer (effect size = 1.10, 95% confidence interval [CI] = 1.05-1.15). When we considered mode of absorption, respiratory inhalation increased the risk of prostate cancer (1.10, 95% CI = 1.05-1.14). Both environmental and occupational exposure increased the risk of prostate cancer (1.25, 95% CI = 1.01-1.48; and 1.07, 1.04-1.10, respectively). For type of fibers, the amosite group had an increased risk of prostate cancer (1.12, 95% CI = 1.05-1.19), and there were no significant results for the chrysotile/crocidolite group. The risk was higher in Europe (1.12, 95% CI = 1.05-1.19), without significant results in other continents.Discussion: Asbestos exposure seems to increase prostate cancer risk. The main mechanism of absorption was respiratory. Both environmental and occupational asbestos exposure were linked to increased risk of prostate cancer.Conclusion: Patients who were exposed to asbestos should possibly be encouraged to complete more frequent prostate cancer screening.

Fluoro-edenite (FE), an asbestiform fiber, is responsible for many respiratory pathologies: chronic obstructive diseases, pleural plaques, fibrosis, and malignant mesothelioma. Macrophage migration inhibitory factor (MIF) is one of the first cytokines produced in response to lung tissue damage. Heme oxygenase-1 (HO-1) is a protein with protective effects against oxidative stress. It is up regulated by several stimuli including pro-inflammatory cytokines and factors that promote oxidative stress. In this research, the in vivo model of sheep lungs naturally exposed to FE was studied in order to shed light on the pathophysiological events sustaining exposure to fibers, by determining immunohistochemical lung expression of MIF and HO-1. Protein levels expression of HO-1 and MIF were also evaluated in human primary lung fibroblasts after exposure to FE fibers in vitro. In exposed sheep lungs, MIF and HO-1 immunoexpression were spread involving the intraparenchymal stroma around bronchioles, interstitium between alveoli, alveolar epithelium and macrophages. High MIF immunoexpression prevails in macrophages. Similar results were obtained in vitro, but significantly higher values were only detected for HO-1 at concentrations of 50 and 100 μg/mL of FE fibers. MIF and HO-1 expressions seem to play a role in lung self-protection against uncontrolled chronic inflammation, thus counteracting the strong link with cancer development, induced by exposure to FE. Further studies will be conducted in order to add more information about the role of MIF and HO-1 in the toxicity FE-induced.

Fluoro-edenite (FE) is a silicate mineral identified in the lava products of Monte Calvario from stone quarries located in the southeast of Biancavilla, a small city of the Etnean volcanic complex (Sicily, Italy). Inhalation of FE fibers has been associated with a higher incidence of Malignant Mesothelioma (MM), a highly aggressive neoplasm of the serosal membranes lining the pleural cavity. Only 5% of MM patients are diagnosed at an early stage and the median survival is approximate 6–12 months. Many diagnostic biomarkers have been proposed for MM. Several studies demonstrated that microRNAs (miRNAs) may be used as good non-invasive diagnostics, as well as prognostic biomarkers for various human diseases, including cancer. On these bases, the aim of the present study was to identify a set of miRNAs involved in the development and progression of MM and potentially used as diagnostic biomarkers. For these purposes, in silico analyses were performed on healthy/exposed to asbestos fibers subjects vs. patients with MM. These analyses revealed a set of miRNAs strictly involved in MM by merging the lists of miRNAs found differentially expressed in the three miRNA expression datasets analyzed. The result of these computational evaluations allowed the execution of functional in vitro experiments performed on normal pleural mesothelial cell line (MeT-5A) and MM cell line (JU77) in order to test the carcinogenetic effects and epigenetic modulation induced by FE exposure. The in vitro results showed that the expression levels of hsa-miR-323a-3p vary significantly in both supernatant- and cell-derived miRNAs derived from treated and untreated cells. Secreted and cellular hsa-miR-101–3p in MeT-5A treated with FE fibers and JU77 cells showed different trends of expression. As regard hsa-miR-20b-5p, there was no differential expression between secreted and cellular hsa-miR-20b-5p. This miRNA has been shown a significant up-regulation in JU77 cells vs. control and treated MeT-5A. As a future plan, translational analyses will be performed on a subset of patients chronically exposed to FE fibers to further verify the clinical role of such miRNAs in high-risk individuals and their possible use as biomarkers of FE exposure or MM early onset.