A growing body of evidence supports an association between systemic autoimmune disease and exposure to amphibole asbestos, a form of asbestos typically with straight, stiff, needle-like fibers that are easily inhaled. While the bulk of this evidence comes from the population exposed occupationally and environmentally to Libby Amphibole (LA) due to the mining of contaminated vermiculite in Montana, studies from Italy and Australia are broadening the evidence to other sites of amphibole exposures. What these investigations have done, that most historical studies have not, is to evaluate amphibole asbestos separately from chrysotile, the most common commercial asbestos in the United States. Here we review the current and historical evidence summarizing amphibole asbestos exposure as a risk factor for autoimmune disease. In both mice and humans, amphibole asbestos, but not chrysotile, drives production of both antinuclear autoantibodies (ANA) associated with lupus-like pathologies and pathogenic autoantibodies against mesothelial cells that appear to contribute to a severe and progressive pleural fibrosis. A growing public health concern has emerged with revelations that a) unregulated asbestos minerals can be just as pathogenic as commercial (regulated) asbestos, and b) bedrock and soil occurrences of asbestos are far more widespread than previously thought. While occupational exposures may be decreasing, environmental exposures are on the rise for many reasons, including those due to the creation of windborne asbestos-containing dusts from urban development and climate change, making this topic an urgent challenge for public and heath provider education, health screening and environmental regulations.

From 1954 to 1983, a vermiculite processing facility operated near the Honolulu airport and processed raw material from the Libby, Montana mine, which is now well known for the high asbestos content of its clay deposits. The factory was closed in 1983 due to health hazard concerns, and remediation was performed in 2001 as part of the Libby mine superfund project. However, because of close proximity of the closed-down facility to residential areas of metropolitan Honolulu, some concerns remain regarding the possible environmental persistence of the harmful contaminant. To assess the dispersion of asbestos-contaminated vermiculite and explore the impact of trade winds on its distribution, air samples, and soil samples were collected from multiple locations near the former vermiculite plant. Polarized light microscopy was employed to identify elongated minerals, including potential asbestos. Quantitative mineralogical analysis utilizing X-ray powder diffraction and Rietveld refinement revealed an average content of approximately 7% vermiculite and 4% tremolite at the site. The asbestiform nature of tremolite was confirmed through X-ray micro-diffraction. Detailed analysis of airborne samples using transmission electron microscopy revealed no detectable levels of asbestos fibers in the vicinity of the former processing facilities, but the possibility of asbestos fibers becoming airborne due to mechanical disturbance during dry weather cannot be ruled out.

Fluoroedenite-induced pleural mesothelioma (FE-induced-PM) is a rare and small subset of PM that shares with its asbestos-induced counterpart the same aggressive biological behavior and poor prognosis, but that differs from it from a pathogenetic point of view as it is associated with exposure to fluoroedenite, a carcinogenic agent that shows similarities with tremolite amphibolic asbestos fibers. Although it has been demonstrated that asbestos-induced PMs frequently harbor CDKN2A homozygous deletion and that the immunohistochemical loss of MTAP may represent a cheap and reliable surrogate marker for this molecular alteration, little is known about the molecular landscape and the reliability of MTAP immunohistochemistry in this peculiar subset of PM. The study herein presented investigated the prevalence of CDKN2A homozygous deletion and its concordance with MTAP immunohistochemical status on a cohort of 10 cases of FE-induced-PM from patients with environmental exposure to FE fibers, who were residents in the small town of Biancavilla (Sicily, Italy) or nearby areas. CDKN2A homozygous deletions were found in 3 out of 10 cases (30%) and all these cases showed concomitant cytoplasmic loss of MTAP with a concordance rate of 100%. Despite the relatively low number of cases included in our series, MTAP immunohistochemistry seemed to represent a reliable immunohistochemical surrogate marker of CDKNA homozygous deletion even in this subset of PMs.

Pleural mesothelioma is a devastating malignancy primarily associated with asbestos exposure. However, emerging evidence suggests that exposure to fluoro-edenite fibers, a naturally occurring mineral fiber, can also lead to the development of pleural mesothelioma. In this study, based on the hypothesis that pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-preferring receptor (PAC1R) expressions could be dysregulated in pleural mesothelioma samples and that they could potentially act as diagnostic or prognostic biomarkers, we aimed to investigate the immunohistochemical expression of PACAP and PAC1R in pleural biopsies from patients with pleural mesothelioma exposed to fluoro-edenite fibers. A total of 12 patients were included in this study, and their biopsies were processed for immunohistochemical analysis to evaluate the expression of PACAP and its receptor. The study revealed a correlation between the overexpression of PACAP and PAC1R and shorter overall survival in patients with malignant mesothelioma. These findings suggest that PACAP and PAC1R expression levels could serve as potential prognostic biomarkers for malignant mesothelioma. Furthermore, the immunohistochemical analysis of PACAP and PAC1R may provide valuable information for clinicians to guide therapeutic decisions and identify patients with poorer prognosis.

It has long been recognized that amphibole minerals, such as cleavage fragments of tremolite and anthophyllite, may exist in some talc deposits. We reviewed the current state of the science regarding the factors influencing mesotheliogenic potency of cleavage fragments, with emphasis on those that may co-occur in talc deposits, including dimensional and structural characteristics, animal toxicology, and the most well-studied cohort exposed to talc-associated cleavage fragments. Based on our review, multiple lines of scientific evidence demonstrate that inhaled cleavage fragments associated with talc do not pose a mesothelioma hazard.

Asbestos and BAP1 germline mutations are risk factors for malignant mesothelioma (MM). While it is well accepted that amphibole asbestos is carcinogenic, the role of serpentine (chrysotile) asbestos in MM has been debated. To address this controversy, we assessed whether minimal exposure to chrysotile could significantly increase the incidence and rate of MM onset in germline Bap1-mutant mice. With either crocidolite or chrysotile, and at each dose tested, MMs occurred at a significantly higher rate and earlier onset time in Bap1-mutant mice than in wild-type littermates. To explore the role of gene-environment interactions in MMs from Bap1-mutant mice, we investigated proinflammatory and protumorigenic factors and the tumor immune microenvironment (TIME). IHC and immunofluorescence staining showed an increased number of macrophages in granulomatous lesions and MMs. The relative number of CD163-positive (CD163+) M2 macrophages in chrysotile-induced MMs was consistently greater than in crocidolite-induced MMs, suggesting that chrysotile induces a more profound immunosuppressive response that creates favorable conditions for evading immune surveillance. MMs from Bap1-mutant mice showed upregulation of CD39/CD73-adenosine and C-C motif chemokine ligand 2 (Ccl2)/C-C motif chemokine receptor 2 (Ccr2) pathways, which together with upregulation of IL6 and IL10, promoted an immunosuppressive TIME, partly by attracting M2 macrophages. Interrogation of published human MM RNA sequencing (RNA-seq) data implicated these same immunosuppressive pathways and connections with CD163+ M2 macrophages. These findings indicate that increased M2 macrophages, along with upregulated CD39/CD73-adenosine and Ccl2/Ccr2 pathways, contribute to an immunosuppressive TIME in chrysotile-induced MMs of Bap1-mutant mice, suggesting that immunotherapeutic strategies targeting protumorigenic immune pathways could be beneficial in human BAP1 mutation carriers who develop MM.
UNASSIGNED: We show that germline Bap1-mutant mice have enhanced susceptibility to MM upon minimal exposure to chrysotile asbestos, not only amphibole fibers. Chrysotile induced a more profound immune tumor response than crocidolite in Bap1-mutant mice by upregulating CD39/CD73-adenosine and Ccl2/Ccr2 pathways and recruiting more M2 macrophages, which together contributed to an immunosuppressive tumor microenvironment. Interrogation of human MM RNA-seq data revealed interconnected immunosuppressive pathways consistent with our mouse findings.

OBJECTIVE: In Italy, the highest pleural cancer mortality and incidence have been observed among Italian regions where the 2 largest Italian shipyards were (and are) located. The objective of this study was to assess the exposure-response relationship for mesothelioma among male workers employed in the Monfalcone, Italy, shipyard.
METHODS: We conducted a necropsy-based case-control study. Cases (N = 102) were mesothelioma decedents and controls were those with lung cancer (N = 84). Complete job histories were available; the lung fibre content was measured using a scanning electron microscope with X-ray fluorescence, after sample preparation according to the European Respiratory Society guidelines. Odds ratios and 95% confidence intervals of mesothelioma by fibre type and lung fibre burden, as a categorical or continuous variable, were assessed by unconditional logistic regression, adjusted for age and time since exposure cessation. Analyses for the amphibole and chrysotile lung fibre burden were mutually adjusted. We calculated a cumulative exposure index by applying a job-exposure matrix to the job histories of study cases and assessed its correlation with the lung fibre burden.
RESULTS: We found an odds ratio of 22.0 (confidence intervals 5.66-85.7) for the highest lung fibre burden category (mean 43.8 million total asbestos fibres per gram of dry tissue) compared with the reference (mean 0.48). Using log10-transformed lung fibre burden, we found that the odds ratio was 3.71 (confidence intervals 2.03-6.79) for a 10-fold lung fibre burden increase. Results for the amphibole lung fibre burden were similar. Odds ratios increased over chrysotile lung fibre burden categories (P-trend = 0.025), and the odds ratio for a 10-fold increase was 4.73 (confidence intervals 0.32-70.4).
CONCLUSIONS: The cumulative exposure index was correlated with total and amphibole lung fibre burden, but not with chrysotile lung fibre burden. Mesothelioma risk was proportional to total, amphibole, and chrysotile lung fibre burden in shipyard workers.

UNASSIGNED: Tissue from a 77-year-old man diagnosed with mesothelioma was referred with a request for identification of the presence of fibrous structures in tissue samples. The individual\'s work history including working as a \"mucker\" at a specific \"industrial\" talc mine.
UNASSIGNED: Ferruginous bodies in the tissue digests as well as asbestos fibers were found. A bulk sample of a talc containing product from that mine was also analyzed.
UNASSIGNED: The correlation between the unique asbestos mineral/fibrous content of the talc to which he was exposed and findings of the same type of asbestos found in his lung is discussed. The type of asbestos found (tremolite) is a \"non-commercial\" type of asbestos that has been identified in some talc deposits. Tremolite, like all forms of asbestos is a causative agent for mesothelioma-the disease from which this individual suffered.

Bone tissue engineering scaffolds may provide a potential strategy for onlay bone grafts for oral implants. For determining the fate of scaffold biomaterials and osteogenesis effects, the host immune response is crucial. In the present study, bredigite (BRT) bioceramic scaffolds with an ordered arrangement structure (BRT-O) and a random morphology (BRT-R) were fabricated. The physicochemical properties of scaffolds were first characterized by scanning electron microscopy, mechanical test and micro-Fourier transform infrared spectroscopy. In addition, their osteogenic and immunomodulatory properties in an onlay grafting model were investigated. In vitro, the BRT-O scaffolds facilitated the macrophage polarization towards a pro-regenerative M2 phenotype, which subsequently facilitated the migration and osteogenic differentiation of bone marrow-derived mesenchymal stem cells. In vivo, an onlay grafting model was successfully established in the cranium of rabbits. In addition, the BRT-O scaffolds grafted on rabbit cranium promoted bone regeneration and CD68 + CD206 + M2 macrophage polarization. In conclusion, the 3D-printed BRT-O scaffold presents as a promising scaffold biomaterial for onlay grafts by regulating the local immune microenvironment.

BACKGROUND: Nephrite is an asbestos mineral composed of tremolite and actinolite. Fengtian is a community where nephrite was mined between 1970 and 1980 and asbestos was mined between 1960 and 1985. The lung cancer risk to the surrounding community is unknown.
OBJECTIVE: To analyse the trend of lung cancer caused by environmental contamination from nephrite mining.
METHODS: We conducted a field survey of nephrite mines and tracked new cases of lung cancer from 1980 to 2019. We calculated the age-standardized incidence rates (ASIRs) and applied join-point regression to examine the lung cancer trend. We assessed the age effect, period effect, and birth cohort effect on lung cancer risk.
RESULTS: The nephrite mines were contaminated with chrysotile and tremolite/actinolite asbestos. A total of 278 new cases of lung cancer were reported during the study period. There was an apparent age effect and a slight period effect for lung cancer. After adjustment for the age and period effects, the birth cohort born between 1970 and 1980 during the period of nephrite mass production had the highest relative risk compared with other birth cohorts. The ASIR of lung cancer increased significantly from 1980 to 2010 (the annual percentage change = 6.8 %, 95 % CI: 4.0-9.7 %, P < 0.01) and then decreased 30 years after the cessation of nephrite jade mining.
CONCLUSIONS: Nephrite mining increases the risk of lung cancer in nearby communities.