Expression of stathmin in asbestos-like fibers-induced mesothelioma: A preliminary report

Background. Mesothelioma is strongly associated with exposure to asbestos fibers, however, recent studies have also linked exposure to "naturally occurring asbestos" fibers with this disease. Fluoroedenite, a silicate mineral found in the southeast of Biancavilla (Sicily, Italy), has been identified as a potential risk factor for mesothelioma. Unfortunately, this cancer often has a poor prognosis, and current diagnostic and prognostic biomarkers are inadequate. Histological subtype, gender, and age at diagnosis are the most significant parameters for mesothelioma. Stathmin, a cytosolic protein that regulates cell growth and migration and is overexpressed in many human malignancies, has not yet been linked to mesothelioma survival or clinical-pathological variables. Aim. The aim of this study was to investigate the immunohistochemical expression of stathmin in ten mesothelioma tissue samples with available clinical and follow-up data. Material and Methods. Paraffin-embedded tissue samples from ten mesothelioma patients were processed for immunohistochemical analyses to evaluate stathmin expression. Results. Our findings suggest that stathmin overexpression is associated with shorter overall survival in patients with mesothelioma. Furthermore, stathmin expression was significantly correlated with the survival time of mesothelioma patients. Conclusion. Our results suggest that stathmin expression may serve as a potential prognostic biomarker for mesothelioma. This biomarker could be used to promptly identify patients with poor prognosis and to guide clinicians in the selection of treatment options

Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy

none67si: Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in genes such as TYMP and POLG, have been linked to these rare diseases. The human genome encodes three DNA ligases, of which only one, ligase III (LIG3), has a mitochondrial splice variant and is crucial for mitochondrial health. We investigated the effect of reduced LIG3 activity and resulting mitochondrial dysfunction in seven patients from three independent families, who showed the common occurrence of gut dysmotility and neurological manifestations reminiscent of mitochondrial neurogastrointestinal encephalomyopathy. DNA from these patients was subjected to whole exome sequencing. In all patients, compound heterozygous variants in a new disease gene, LIG3, were identified. All variants were predicted to have a damaging effect on the protein. The LIG3 gene encodes the only mitochondrial DNA (mtDNA) ligase and therefore plays a pivotal role in mtDNA repair and replication. In vitro assays in patient-derived cells showed a decrease in LIG3 protein levels and ligase activity. We demonstrated that the LIG3 gene defects affect mtDNA maintenance, leading to mtDNA depletion without the accumulation of multiple deletions as observed in other mitochondrial disorders. This mitochondrial dysfunction is likely to cause the phenotypes observed in these patients. The most prominent and consistent clinical signs were severe gut dysmotility and neurological abnormalities, including leukoencephalopathy, epilepsy, migraine, stroke-like episodes, and neurogenic bladder. A decrease in the number of myenteric neurons, and increased fibrosis and elastin levels were the most prominent changes in the gut. Cytochrome c oxidase (COX) deficient fibres in skeletal muscle were also observed. Disruption of lig3 in zebrafish reproduced the brain alterations and impaired gut transit in vivo. In conclusion, we identified variants in the LIG3 gene that result in a mitochondrial disease characterized by predominant gut dysmotility, encephalopathy, and neuromuscular abnormalities.This work was supported by Telethon Grant GGP15171 to E.B. and R.D.G. and by a donation from Kobe city to the Department of General Pediatrics, Kobe University Graduate School of Medicine (K550003302). S.C. was supported by a Dutch Cancer Foundation grant (KWF11011). V.C. and A.M. were supported by the Italian Ministry of Health (“Ricerca Corrente” funding). R.D.G. is the recipient of grants from University of Ferrara (FAR and FIR funds).openBonora, Elena; Chakrabarty, Sanjiban; Kellaris, Georgios; Tsutsumi, Makiko; Bianco, Francesca; Bergamini, Christian; Ullah, Farid; Isidori, Federica; Liparulo, Irene; Diquigiovanni, Chiara; Masin, Luca; Rizzardi, Nicola; Cratere, Mariapia Giuditta; Boschetti, Elisa; Papa, Valentina; Maresca, Alessandra; Cenacchi, Giovanna; Casadio, Rita; Martelli, Pierluigi; Matera, Ivana; Ceccherini, Isabella; Fato, Romana; Raiola, Giuseppe; Arrigo, Serena; Signa, Sara; Sementa, Angela Rita; Severino, Mariasavina; Striano, Pasquale; Fiorillo, Chiara; Goto, Tsuyoshi; Uchino, Shumpei; Oyazato, Yoshinobu; Nakamura, Hisayoshi; Mishra, Sushil K; Yeh, Yu-Sheng; Kato, Takema; Nozu, Kandai; Tanboon, Jantima; Morioka, Ichiro; Nishino, Ichizo; Toda, Tatsushi; Goto, Yu-Ichi; Ohtake, Akira; Kosaki, Kenjiro; Yamaguchi, Yoshiki; Nonaka, Ikuya; Iijima, Kazumoto; Mimaki, Masakazu; Kurahashi, Hiroki; Raams, Anja; MacInnes, Alyson; Alders, Mariel; Engelen, Marc; Linthorst, Gabor; de Koning, Tom; den Dunnen, Wilfred; Dijkstra, Gerard; van Spaendonck, Karin; van Gent, Dik C; Aronica, Eleonora M; Picco, Paolo; Carelli, Valerio; Seri, Marco; Katsanis, Nicholas; Duijkers, Floor A M; Taniguchi-Ikeda, Mariko; De Giorgio, RobertoBonora, Elena; Chakrabarty, Sanjiban; Kellaris, Georgios; Tsutsumi, Makiko; Bianco, Francesca; Bergamini, Christian; Ullah, Farid; Isidori, Federica; Liparulo, Irene; Diquigiovanni, Chiara; Masin, Luca; Rizzardi, Nicola; Cratere, Mariapia Giuditta; Boschetti, Elisa; Papa, Valentina; Maresca, Alessandra; Cenacchi, Giovanna; Casadio, Rita; Martelli, Pierluigi; Matera, Ivana; Ceccherini, Isabella; Fato, Romana; Raiola, Giuseppe; Arrigo, Serena; Signa, Sara; Sementa, Angela Rita; Severino, Mariasavina; Striano, Pasquale; Fiorillo, Chiara; Goto, Tsuyoshi; Uchino, Shumpei; Oyazato, Yoshinobu; Nakamura, Hisayoshi; Mishra, Sushil K; Yeh, Yu-Sheng; Kato, Takema; Nozu, Kandai; Tanboon, Jantima; Morioka, Ichiro; Nishino, Ichizo; Toda, Tatsushi; Goto, Yu-Ichi; Ohtake, Akira; Kosaki, Kenjiro; Yamaguchi, Yoshiki; Nonaka, Ikuya; Iijima, Kazumoto; Mimaki, Masakazu; Kurahashi, Hiroki; Raams, Anja; MacInnes, Alyson; Alders, Mariel; Engelen, Marc; Linthorst, Gabor; de Koning, Tom; den Dunnen, Wilfred; Dijkstra, Gerard; van Spaendonck, Karin; van Gent, Dik C; Aronica, Eleonora M; Picco, Paolo; Carelli, Valerio; Seri, Marco; Katsanis, Nicholas; Duijkers, Floor A M; Taniguchi-Ikeda, Mariko; De Giorgio, Robert

High HOMA-IR Index in Healthcare Shift Workers

Background and objectives: Evidence shows that shift work may be correlated with insulin resistance (IR). Therefore its estimation in clinical and prevention practice is of great significance. A cross-sectional study was performed to examine the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) Index among healthcare shift workers (HCSW). Materials and Methods: A total of 272 healthcare workers (HCWs) were invited to participate in the study within an occupational surveillance framework, 137 were HCSW while 135 were healthcare non-shift workers (HCNSW). Fasting glucose, insulin, and HOMA-IR Index were evaluated in each participant and correlated with shift workers. Results: Indicators of glucose metabolism were significantly higher in HCSW p < 0.001, and logistic regression analysis confirmed a significant positive association between increased values of HOMA-IR Index and shift workers (p < 0.05). Conclusions: Shift work could be a risk factor in developing insulin resistance and metabolic syndrome

Cadmium exposure and prostate cancer: insights, mechanisms and perspectives

Cadmium (Cd) is a metal found in group 12 (IIB) of the periodic table of elements together with zinc, a metal with which it is often conjugated in nature. Occupational exposure to Cd occurs in many industrial settings, by cigarette smoking, diet and due to environmental pollution. International Agency for Research on Cancer and other epidemiological studies suggested that Cd can lead to prostate cancer and likely to kidney and lung cancers. Although epidemiological studies seem to point towards such an association, the in vitro studies have not been compelling. The aim of this article is to summarize current knowledge about the association of Cd exposure and prostate cancer, that suggests that new studies to show the role of Cd in the pathogenesis of prostatate cancer

Abnormal Plasma Cell Disorders in Refinery Waste Workers

A monoclonal gammopathy of undetermined significance (MGUS) may develop into a multiple myeloma or a correlated lymphoproliferative malignancy with a progress rate of 1% per year. The immune status, occupational-environmental risk factors, and hereditary factors may influence the risk of developing MGUS. We investigated the prevalence of MGUS in 77 refinery waste workers. They were all males, averagely aged 36, with a mean working history of 18.5 years and working in the dump for about 4.2 years. After analyzing the results of standard serum electrophoresis migrations, 16% of cases (n = 12) showed levels beyond the normal ranges. In all 12 samples we observed an increase of gamma component: 67%, IgG; 17%, IgM; 8%, IgA; 8%, oligoclonal. Workers were exposed to hazardous refinery waste. After the biological monitoring of urine samples for metals and t,t-muconic acid, no extra-range values were observed. The multivariate analysis shows, however, that cigarette smoking and residence near industrial sites are significantly (p < 0.001) associated with a high risk of MGUS development; while no association was found with occupational exposure. Additional attention might be paid in particular to these conditions in epidemiological studies and further larger, prospective, population-based researches appear warranted to evaluate the strength of any positive association

Acylated anthocyanins from sprouts of Raphanus sativus cv. Sango: Isolation, structure elucidation and antioxidant activity

Little is known on structure\u2013activity relationships of antioxidant anthocyanins. Raphanus sativus cv Sango sprouts are among the richest sources (270 mg/100 g fresh weight). We isolated from sprouts\u2019 juice 9 acylated anthocyanins, including 4 new compounds. All comprise a cyanidin core bearing 3\u20134 glucose units, multiply acylated with malonic and phenolic acids (ferulic and sinapic). All compounds were equally effective in inhibiting the autoxidation of linoleic acid in aqueous micelles, with rate constant for trapping peroxyl radicals kinh = (3.8 \ub1 0.7) 104 M\u20131 s\u20131 at 37 C. In acetonitrile solution kinh varied with acylation: (0.9\u20132.1) 105 M\u20131 s\u20131 at 30 C. Each molecule trapped a number n of peroxyl radicals ranging from 4 to 7. Anthocyanins bearing sinapic acid were more effective than those bearing the ferulic moiety. Under identical settings, deacylated cyanin, ferulic and sinapic acids had kinh of 0.4 105, 0.3 105 and 1.6 105 M\u20131 s\u20131 respectively, with n ranging 2\u20133. Results show the major role of acylation on antioxidant performance

Work Ability after Breast Cancer: Study of Healthcare Personnel Operating in a Hospital of South Italy

Breast cancer (BrC) treatment can produce disabilities that often impact the quality of daily life and impact the social and working relationships of the patient. This paper looked into the remaining work ability in a group of female healthcare personnel (HCPs) with BrC in Southern Italy. Each HCP was subjected to a medical check, routine blood tests, and a questionnaire on the work ability index (WAI). Of 980 (100%) HCWs undergoing health control, 6% (n = 54) had experienced BRC, and only 66.6% (n = 36) agreed to take part in the study. A total of 28 (78%) were on night shifts. The WAI score was quite low in 5 (13.8%) cases, moderate in 10 (27.7%) cases, good in 14 (38.8%) cases, and excellent in 7 (19.5%) HCWs. Among all health figures, in nurses as well as technical staff, lower WAI scores were observed. HCWs reported various comorbidities, which affected WAI score, such as limited mobility in the upper limbs, arm/shoulder pain, numbness, and lymphoedema. The main complication that negatively affects any work activity is the morbidity in the upper limbs. This seems to affect the ability to perform tasks, and the re-entry to work is highlighted on sick leave days

Work Ability after Breast Cancer: Study of Healthcare Personnel Operating in a Hospital of South Italy

Breast cancer (BrC) treatment can produce disabilities that often impact the quality of daily life and impact the social and working relationships of the patient. This paper looked into the remaining work ability in a group of female healthcare personnel (HCPs) with BrC in Southern Italy. Each HCP was subjected to a medical check, routine blood tests, and a questionnaire on the work ability index (WAI). Of 980 (100%) HCWs undergoing health control, 6% (n = 54) had experienced BRC, and only 66.6% (n = 36) agreed to take part in the study. A total of 28 (78%) were on night shifts. The WAI score was quite low in 5 (13.8%) cases, moderate in 10 (27.7%) cases, good in 14 (38.8%) cases, and excellent in 7 (19.5%) HCWs. Among all health figures, in nurses as well as technical staff, lower WAI scores were observed. HCWs reported various comorbidities, which affected WAI score, such as limited mobility in the upper limbs, arm/shoulder pain, numbness, and lymphoedema. The main complication that negatively affects any work activity is the morbidity in the upper limbs. This seems to affect the ability to perform tasks, and the re-entry to work is highlighted on sick leave days