The role of MicroRNAs as early biomarkers of asbestos-related lung cancer: A systematic review and meta-analysis.

BACKGROUND: Asbestos is still the leading cause of occupational cancer mortality worldwide. Asbestos-related lung cancer (LC) and malignant pleural mesothelioma (MPM) prognosis is still poor especially at advanced stage, so early diagnosis biomarkers are needed. MicroRNAs (miRNAs) have been proposed as potential early diagnostic biomarkers of asbestos-related LC and MPM. AIM: To evaluate the role of miRNAs as diagnostic and prognostic biomarkers of asbestos-related LC and MPM by performing a literature systematic review and meta-analysis. METHODS: MEDLINE, EMBASE via Ovid, PUBMED and Cochrane library databases were systematically searched up to April 2023 to identify relevant articles. A grey literature search was also conducted using the Google Scholar platform. MeSH and free text terms for 'asbestos', 'occupational exposure', 'lung cancer', 'mesothelioma' and 'miRNAs' were used to search the literature. Our systematic review protocol was registered in the PROSPERO database. Study quality was assessed via the Newcastle-Ottawa Scale. RESULTS: From the search, 331 articles were retrieved, and, after applying our selection criteria, and exclusion of one study for poor quality, 27 studies were included in the review. Most of the studies were hospital-based case-control, conducted in Europe, and evaluated MPM among men only. MiRNAs expression was measured mainly in plasma or serum. MiR-126, miR-132-3p, and miR-103a-3p were the most promising diagnostic biomarkers for MPM, and we estimated a pooled area under the curve (AUC) of 85 %, 73 %, and 50 %, respectively. In relation to MPM prognosis, miR-197­3p resulted associated with increased survival time. MiR-126, alone and combined with miR-222, was confirmed associated also to LC diagnosis, together with miR-1254 and miR-574-5p; no miRNA was found associated to LC prognosis. CONCLUSION: Based on our systematic literature review there is suggestive evidence that the expression of specific miRNAs in the blood serum or plasma are associated with asbestos-related LC and MPM diagnosis and prognosis. Further large longitudinal studies are urgently needed to validate these findings and elucidate the underlying mechanisms given the potential important implications for patients' survival.

Microbial quality of equine frozen semen.

Bacteriological surveillance is little applied in management of equine frozen semen but it is quite important to verify the microbial contamination in order to find out the chance of transmission of pathology to the mare in AI. Authors describe a qualitative and quantitative analysis for bacterial contamination on long time (3-17 years) equine frozen semen stored in liquid nitrogen. The semen checked, produced in Italy and in another Europe country, was cryopreserved in liquid nitrogen inside sealed plastic straws. One hundred and ten straws were checked out for pathogenic and no pathogenic bacteria, aerobes and anaerobes and fungi (moulds and yeasts). The Total Microbial Charge was quite variable with an average of about 1.4 x 10(5)CFU/ml. Mostly the microbial agents identified were fungi (17.5%), Enterobacter-coccus spp. (15%), Pseudomonas spp. (6.25%), Stenothophomonas maltophila (6.25%) and anaerobic bacteria like Propionibacterium granulosum (7.5%) and Clostridium spp. (3.75%). 3.75% were unidentified Gram-negative rod and cocci. Streptococcus spp., Staph. aureus, E. coli, Th. equigenitalis and Mycoplasma spp. were not detected. The most represented species were Enterobacter-coccus spp. (1.1 x 10(5)CFU/ml), St. maltophila (8 x 10(4)CFU/ml) and Pr. granulosum (7 x 10(4)CFU/ml) while yeast and even more moulds were little abundant (4.7 x 10(4) and 3.4 x 10(4)CFU/ml respectively). The knowledge of equine frozen semen microbial quality is essential to check out transmission of venereal disease and improve the quality of cryopreserved germplasm.

A novel PSEN2 mutation associated with a peculiar phenotype.

BACKGROUND: Mutations of presenilin 2 gene are a rare cause of familial Alzheimer disease (AD). We describe an Italian family with hereditary dementia associated with a novel mutation in the presenilin 2 gene. METHODS: Clinical investigations of the diseased subjects; interviews with relatives; studies of medical records; pedigree analysis; and neuroradiologic, neuropathologic, and molecular genetic studies were carried out in the pedigree. RESULTS: Genetic analysis showed a novel PSEN2 A85V mutation present in the proband and in all analyzed affected members, in a subject presenting with an amnesic mild cognitive impairment, and in a young, still asymptomatic subject. The proband showed a clinical phenotype indicative of Lewy body dementia and the neuropathologic examination demonstrated the presence of unusually abundant and widespread cortical Lewy bodies in addition to the hallmark lesions of AD. Other affected members exhibited a clinical phenotype typical of AD. CONCLUSIONS: Our findings add complexity to the spectrum of atypical phenotypes associated with presenilin mutations and should then be taken into account when considering the nosography of neurodegenerative diseases. They also support previous data that specific mutations of genes associated with familial Alzheimer disease may influence the presence and extent of Lewy bodies.

PEN-2 gene mutation in a familial Alzheimer's disease case.

Genetic evidence indicates a central role of cerebral accumulation of beta-amyloid (Abeta) in the pathogenesis of Alzheimer's disease (AD). Beside presenilin 1 and 2, three other recently discovered proteins (Aph 1, PEN 2 and nicastrin) are associated with gamma-secretase activity, the enzymatic complex generating Abeta. Alterations in genes encoding these proteins were candidates for a role in AD. The PEN 2 gene was examined for unknown mutations and polymorphisms in sporadic and familial Alzheimer patients. Samples from age-matched controls (n=253), sporadic AD (SAD, n=256) and familial AD (FAD, n=140) were screened with DHPLC methodology followed by sequencing. Scanning the gene identified for the first time a missense mutation (D90N) in a patient with FAD. Three intronic polymorphisms were also identified, one of which had a higher presence of the mutated allele in AD subjects carrying the allele epsilon4 of apolipoprotein E than controls. The pathogenic role of the PEN-2 D90N mutation in AD is not clear, but the findings might lead to new studies on its functional and genetic role.

P300 and executive function alterations: possible links in a case of Morgagni-Stewart-Morel syndrome.

To evaluate possible cause-effect relationships between hyperostosis frontalis interna and cognitive dysfunction, we performed a neurophysiological (event-related potentials, ERPs) and neuropsychological study in a case of Morgagni-Stewart-Morel (MSM) syndrome associated with frontal lobe compression. Neuropsychological evaluation evidenced selective impairment of executive function. Visual and auditory oddball ERPs revealed delayed P300 latency and reduced auditory P300 amplitude with multi-peaked morphology. ERP abnormalities and cognitive dysfunction could be due to the frontal bone-cortex conflict documented by neuroradiological investigations.

Problems of inference from hypothesis-generating studies on lung cancer and occupation based on routine hospital records.

This paper discusses inference from hypothesis-generating studies on occupational risks for lung cancer based on routine hospital records. A hospital-based case-control study on 567 male lung cancer patients and 906 controls provided a practical example. Among possible causes of bias, the effects of poor detail in the occupational information, of a large proportion of exclusions due to incomplete information, of cardiovascular diseases as the prevalent diagnosis among controls, of selecting cases and controls from different hospitals with likely differences in referring areas, and the problem of multiple comparisons are highlighted. Significant excess lung cancer risks were found for farmers, miners, crushers, stonemasons and cement plant workers, and stock handlers and stevedores. Positive findings with small numbers of observations are more likely to be artificially generated, but also the precision of more robust risk estimates may be affected. The limits to inference from hypothesis generating case-control studies based upon routine hospital records, such as in the example described, outweigh the advantage of the ready availability of these data-bases.

Altered pattern of lipid metabolism in patients with lung cancer.

Cholesterol distribution in tumoral tissues and lipid composition in the plasma compartment were determined in patients affected by different histologic types of lung cancer. The results showed that tumoral lung tissues contained 2-fold more total cholesterol and 3.5-fold more esterified cholesterol than normal lung tissues. In the patients the alterations in intracellular cholesterol were also associated with peculiar changes in cholesterol distribution in the plasma compartment. Serum high-density lipoprotein (HDL) cholesterol levels were markedly lower in than in controls. No significant changes in other lipid parameters were observed in these patients. We suggest that the reduced levels of serum HDL cholesterol observed in patients with lung tumors may be a consequence of the disease, probably mediated by the greater utilization of cholesterol for new membrane biogenesis and by the accumulation of esterified cholesterol in tumoral tissues.

Glucose-6-phosphate dehydrogenase deficiency and lung cancer: a hospital based case-control study.

A hospital based case-control study was conducted to test the hypothesis of a lower lung cancer risk in G6PD-deficient subjects. Cases were 156 male patients with lung cancer, admitted to "Binaghi" Hospital, Local Health Unit (USL) 20, Cagliari (Italy), between January 1984 and November 1986. Controls were 235 male patients, admitted to the same hospital in the same time period, for diseases other than cancer (all types) and hemolytic anemia. No decrease of the lung cancer risk was found in G6PD-deficient subjects. This result, in line with recent reports in the literature, suggests that the genetic condition of G6PD deficiency does not provide significant protection against the development of lung cancer in humans.

[Osteoclastoma-like giant cell tumor of the lung]. / Tumore a cellule giganti osteoclastosimili del polmone.

Osteoclastoma-like giant cell tumor of lung. A case of osteoclastoma-like giant cell tumor of the lung is reported. This is an unusual tumor too described in the heart, thyroid, skin, soft tissues and pancreas. AA. studied the tumor's structure and are of opinion that it concerns a primitive nonepithelial neoplasm of the lung.

Hexose monophosphate shunt enzymes in lung tumors from normal and glucose-6-phosphate-dehydrogenase-deficient subjects.

Glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate, dehydrogenase the key enzymes of the hexose monophosphate shunt pathway, were measured in both surrounding and tumoral lung tissues from normal and G6PD-deficient subjects. A significant increase of these enzymatic activities in tumoral tissue was found not only in G6PD-normal patients, but also in G6PD-deficient patients with very low or nonmeasurable G6PD activity in both erythrocytes and normal lung tissue.