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Cytochrome C (cyt C), the protein involved in oxidative phosphorylation, plays several other crucial roles necessary for both cell life and death. Studying natural variants of cyt C offers the possibility to better characterize the structure-to-function relationship that modulates the different activities of this protein. Naturally mutations in human cyt C (G41S and Y48H) occur in the protein central Ω-loop and cause thrombocytopenia 4. In this study, we have investigated the binding of such variants and of wild type (wt) cyt C to synthetic cardiolipin-containing vesicles. The mutants have a lower propensity in membrane binding, displaying higher dissociation constants with respect to the wt protein. Compressibility measurements reveal that both variants are more flexible than the wt, suggesting that the native central Ω-loop is important for the interaction with membranes. Such hypothesis is supported by molecular dynamics simulations. A minimal distance analysis indicates that in the presence of cardiolipin the central Ω-loop of the mutants is no more in contact with the membrane, as it happens instead in the case of wt cyt C. Such finding might provide a hint for the reduced membrane binding capacity of the variants and their enhanced peroxidase activity in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The objectives of the systematic review were to: identify the work sectors at risk for exposure to formaldehyde; investigate the procedures applied to assess occupational exposure; evaluate the reported exposure levels among the different settings. An electronic search of Pubmed, Scopus, Web of Science and ToxNet was carried out for collecting all the articles on the investigated issue published from January 1, 2004 to September 30, 2019. Forty-three papers were included in the review, and evidenced a great number of occupational scenarios at risk for formaldehyde exposure. All the included studies collected data on formaldehyde exposure levels by a similar approach: environmental and personal sampling followed by chromatographic analyses. Results ranged from not detectable values until to some mg m -3 of airborne formaldehyde. The riskiest occupational settings for formaldehyde exposure were the gross anatomy and pathology laboratories, the hairdressing salons and some specific productive settings, such as wooden furniture factories, dairy facilities and fish hatcheries. Notice that formaldehyde, a well-known carcinogen, was recovered in air at levels higher than outdoor in almost all the studied scenarios/activities; thus, when formaldehyde cannot be removed or substituted, targeted strategies for exposure elimination or mitigation must be adopted., (© 2021 The Authors. Indoor Air published by John Wiley & Sons Ltd.)

The interaction of cytochrome c (cyt c) with natural and synthetic membranes is known to be a complex phenomenon, involving both protein and lipid conformational changes. In this paper, we combined infrared and fluorescence spectroscopy to study the structural transformation occurring to the lipid network of cardiolipin-containing large unilamellar vesicles (LUVs). The data, collected at increasing protein/lipid ratio, demonstrate the existence of a multi-phase process, which is characterized by: (i) the interaction of cyt c with the lipid polar heads; (ii) the lipid anchorage of the protein on the membrane surface; and (iii) a long-distance order/disorder transition of the cardiolipin acyl chains. Such effects have been quantitatively interpreted introducing specific order parameters and discussed in the frame of the models on cyt c activity reported in literature.

Silicon nanowires (SiNWs) are attractive functional nanomaterials for biomedical applications. The ability to easily tune their size and density, potential biocompatibility, and knowledge of the chemical activation of SiNWs surface make them natural tools to interact with biological materials. We evaluated the possibility of exploiting SiNWs as carriers to introduce organic compounds into cells. The cellular toxicity and the internalization capacity of free-standing and label-free SiNWs were tested on Buffalo Green Monkey cells (BGM). Confocal fluorescent observation of SiNWs conjugated with fluorescein-polyethylene imine (PEI) confirmed the internalization of the NWs into the Buffalo Green Monkey Cells (BGM).

Cytochrome c, a protein that belongs to class 1 of the c-type cytochrome family, exerts different functions depending on its cellular localization and the conditions in which it operates; therefore, it can be defined as 'extreme multifunctional' protein. It mediates electron-transfer in the respiratory chain and acts as a detoxifying agent to dispose of ROS. In addition, cytochrome c plays a role in cell apoptosis. After its release into the cytosol, the protein binds to APAF-1, activates pro-caspase 9, and triggers an enzymatic cascade leading to cell death. The interaction with cardiolipin, one of the phospholipids making up the mitochondrial membrane, is essential to start apoptosis; the binding partially unfolds cytochrome c, alters the heme pocket region, and facilitates detachment of Met80 from the sixth coordination position of the heme iron. These events change the function of cytochrome c from an electron-transfer shuttle to a peroxidase-like hemoprotein, capable to trigger the process that leads to cell death. This review provides an overview of the key role played by the cytochrome c-cardiolipin interaction in apoptosis. This is not only important per se, it provides interesting perspectives for applications in clinical diagnostics that use the protein as a biomarker., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Workers in the mining industry in altitude are subjected to several risk factors, e.g., airborne silica and low barometric pressure. The aim of this study has been to assess the risks for this work category, evaluating single risk factors as airborne silica, altitude and work shift, and relating them with cardiovascular and ventilatory parameters., Material and Methods: Healthy miners employed in a mining company, Chile, working at varied altitudes, and subjected to unusual work shifts, were evaluated. Cardiovascular and respiratory parameters were investigated. Exposure to airborne silica was evaluated and compared to currently binding exposure limits., Results: At varied altitudes and work shifts, alterations emerged in haemoglobin, ventilation and respiratory parameters, related to employment duration, due to compensatory mechanisms for hypoxia. Haemoglobin increased with altitude, saturation fell down under 90% in the highest mines. The multiple linear regression analysis showed a direct relationship, in the higher mine, between years of exposure to altitude and increased forced vital capacity percent (FVC%), and forced expiratory volume in 1 s (FEV1). An inverse relationship emerged between forced vital capacity (FVC) and years of exposure to airborne silica. In the workplace Mina Subterrànea (MT-3600), statistically significant inverse relationship emerged between the Tiffeneau index and body weight., Conclusions: The working conditions in the mining industry in altitude appeared to be potentially pathogenic; further investigations should be realized integrating risk assessment protocols even in consideration of their undeniable unconventionality. Int J Occup Med Environ Health 2018;31(2):129-138., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

The ability of a C-terminal truncated form of TRAF2 to bind synthetic vesicles has been quantitatively studied by steady-state fluorescence energy transfer from the protein to large unilamellar vesicles (LUVs) prepared with different lipid mixtures. The dissociation constants, the free energy of binding, and the average number of phospholipids interacting with truncated TRAF2 have been evaluated from the corresponding binding curves. The results indicate that the protein strongly interacts with the lipid bilayer, preferentially in the monomeric state. These findings have been discussed in terms of their possible role in the activity of TRAF2 in vivo., (© 2017 International Union of Biochemistry and Molecular Biology, Inc.)

Polyunsaturated fatty acids have been reported to play a protective role in a wide range of diseases characterized by an increased metalloproteinases (MMPs) activity. The recent finding that omega-3 and omega-6 fatty acids exert an anti-inflammatory effect in periodontal diseases has stimulated the present study, designed to determine whether such properties derive from a direct inhibitory action of these compounds on the activity of MMPs. To this issue, we investigated the effect exerted by omega-3 and omega-6 fatty acids on the activity of MMP-2 and MMP-9, two enzymes that actively participate to the destruction of the organic matrix of dentin following demineralization operated by bacteria acids. Data obtained (both in vitro and on ex-vivo teeth) reveal that omega-3 and omega-6 fatty acids inhibit the proteolytic activity of MMP-2 and MMP-9, two enzymes present in dentin. This observation is of interest since it assigns to these compounds a key role as MMPs inhibitors, and stimulates further study to better define their therapeutic potentialities in carious decay.

The interaction between cytochrome c (Cyt c) and cardiolipin (CL) plays a vital role in the early stages of apoptosis. The binding of CL to Cyt c induces a considerable increase in its peroxidase activity that has been attributed to the partial unfolding of the protein, dissociation of the Met80 axial ligand, and formation of non-native conformers. Although the interaction between Cyt c and CL has been extensively studied, there is still no consensus regarding the conformational rearrangements of Cyt c that follow the protein-lipid interaction. To rationalize the different results and gain better insight into the Cyt c-CL interaction, we have studied the formation of the CL complex of the horse heart wild-type protein and selected mutants in which residues considered to play a key role in the interaction with CL (His26, His33, Lys72, Lys73, and Lys79) have been mutated. The analysis was conducted at both room temperature and low temperatures via ultraviolet-visible absorption, resonance Raman, and electron paramagnetic resonance spectroscopies. The trigger and the sequence of CL-induced structural variations are discussed in terms of disruption of the His26-Pro44 hydrogen bond. We unequivocally identify the sixth ligand in the partially unfolded, non-native low-spin state that Cyt c can adopt following the protein-lipid interaction, as a His ligation, ruling out the previously proposed involvement of a Lys residue or an OH - ion.

Cytochrome c undergoes structural variations upon binding of cardiolipin, one of the phospholipids constituting the mitochondrial membrane. Although several mechanisms governing cytochrome c/cardiolipin (cyt c/CL) recognition have been proposed, the interpretation of the process remains, at least in part, unknown. To better define the steps characterizing the cyt c-CL interaction, the role of Lys72 and Lys73, two residues thought to be important in the protein/lipid binding interaction, were recently investigated by mutagenesis. The substitution of the two (positively charged) Lys residues with Asn revealed that such mutations cancel the CL-dependent peroxidase activity of cyt c; furthermore, CL does not interact with the Lys72Asn mutant. In the present paper, we extend our study to the Lys → Arg mutants to investigate the influence exerted by the charge possessed by the residues located at positions 72 and 73 on the cyt c/CL interaction. On the basis of the present work a number of overall conclusions can be drawn: (i) position 72 must be occupied by a positively charged residue to assure cyt c/CL recognition; (ii) the Arg residues located at positions 72 and 73 permit cyt c to react with CL; (iii) the replacement of Lys72 with Arg weakens the second (low-affinity) binding transition; (iv) the Lys73Arg mutation strongly increases the peroxidase activity of the CL-bound protein.

Horse heart carboxymethylated cytc (CM-cytc) displays myoglobin-like properties. Here, the effect of cardiolipin (CL) liposomes on the nitrite reductase activity of ferrous CM-cytc [CM-cytc-Fe(II)], in the presence of sodium dithionite, is reported between pH 5.5 and 7.6, at 20.0 °C. Cytc-Fe(II) displays a very low value of the apparent second-order rate constant for the NO2 (-)-mediated conversion of cytc-Fe(II) to cytc-Fe(II)-NO [k on = (7.3 ± 0.7) × 10(-2) M(-1) s(-1); at pH 7.4], whereas the value of k on for NO2 (-) reduction by CM-cytc-Fe(II) is 1.1 ± 0.2 M(-1) s(-1) (at pH 7.4). CL facilitates the NO2 (-)-mediated nitrosylation of CM-cytc-Fe(II) in a dose-dependent manner, the value of k on for the NO2 (-)-mediated conversion of CL-CM-cytc-Fe(II) to CL-CM-cytc-Fe(II)-NO (5.6 ± 0.6 M(-1) s(-1); at pH 7.4) being slightly higher than that for the NO2 (-)-mediated conversion of CL-cytc-Fe(II) to CL-cytc-Fe(II)-NO (2.6 ± 0.3 M(-1) s(-1); at pH 7.4). The apparent affinity of CL for CM-cytc-Fe(II) is essentially pH independent, the average value of B being (1.3 ± 0.3) × 10(-6) M. In the absence and presence of CL liposomes, the nitrite reductase activity of CM-cytc-Fe(II) increases linearly on lowering pH and the values of the slope of the linear fittings of Log k on versus pH are -1.05 ± 0.07 and -1.03 ± 0.03, respectively, reflecting the involvement of one proton for the formation of the transient ferric form, NO, and OH(-). These results indicate that Met80 carboxymethylation and CL binding cooperate in the stabilization of the highly reactive heme-Fe atom of CL-CM-cytc.

Cytochrome c (cytc) is a small heme-protein located in the space between the inner and the outer membrane of the mitochondrion that transfers electrons from cytc-reductase to cytc-oxidase. The hexa-coordinated heme-Fe atom of cytc displays a very low reactivity toward ligands and does not exhibit significant catalytic properties. However, upon cardiolipin (CL) binding, cytc achieves ligand binding and catalytic properties reminiscent of those of myoglobin and peroxidase. In particular, the peroxidase activity of the cardiolipin-cytochrome c complex (CL-cytc) is critical for the redistribution of CL from the inner to the outer mitochondrial membranes and is essential for the execution and completion of the apoptotic program. On the other hand, the capability of CL-cytc to bind NO and CO and the heme-Fe-based scavenging of reactive nitrogen and oxygen species may affect apoptosis. Here, the ligand binding and catalytic properties of CL-cytc are analyzed in parallel with those of CL-free cytc, myoglobin, and peroxidase to dissect the potential mechanisms of CL in modulating the pro- and anti-apoptotic actions of cytc., (© 2015 International Union of Biochemistry and Molecular Biology.)

Background: Work-related stress is a complex problem requiring a work environment-based assessment. Artists like dancers represent a category of atypical workers potentially at high risk for work-related stress. Aim of our pilot study is to evaluate organizational stress in a population of professional dancers, using the HSE Indicator Tool for Work Related Stress., Methods: We administered the Italian version of the HSE Indicator Tool to 38 ballet dancers, males and females. The questionnaire evaluates 7 key organizational dimensions: demand, control, managers' support, peer support, relationships, role and change., Results: The standards required-ideal conditions are achieved in none of the above-mentioned dimensions. Change is the only dimension for which results fall between the 20th and the 50th percentile, while for other dimensions results fall below the 20th percentile suggesting the need for immediate corrective action. In male dancers an acceptable situation is highlighted for the dimension "change" compared to female dancers. In both sexes there is a high frequency of subjects complaining of verbal abuse, bullying and harassment., Conclusions: Despite the small sample size, our pilot study highlights the presence of heightened levels of organizational stress. Preventive measures targeted towards improving communication between managers and dancers and aimed at team building should be implemented.

Aim: A significant relationship between exposure to cadmium and PAHs from urban air pollution and blood pressure has already been found. The aim of the study is to evaluate if other urban pollutants maintain a similar relationship in outdoor workers., Materials and Methods: 349 subjects of both sexes were enrolled in the study; we evaluated values of environmental and biological monitoring of respirable dust, arsenic, lead, benzene, toluene, xylene and we measured blood pressure (BP) in upright and in supine position; to analyze data we used multiple linear regression. Also we valued our results in the light of those we have obtained in previous research., Results: Multiple linear regression showed no significant results that demonstrate a relationship between BP and these pollutants., Conclusions: The results of our study lead to assume that exposure to urban pollutants studied has not connection with blood pressure, and to retain valid the relationship previously observed for cadmium and PAHs, which seem to be the only pollutants that can affect blood pressure.

Objectives: Everyday outdoor workers are exposed to chemicals including the polycyclic aromatic hydrocarbons (PAHs). The aim of the study is to evaluate the relationship between hydroxypyrene and blood pressure in outdoor workers., Materials and Methods: 374 subjects of both sexes entered the study. We evaluated the assay of urinary hydroxypyrene (1-HOP); their blood pressure (BP) was measured in upright position and in the supine position and the correlation between the levels of 1-HOP and BP was assessed using Pearson test and linear multiple regression., Results: The results obtained show that in the total sample the levels of urinary 1-OHP are negatively associated with systolic and diastolic BP in supine position and in upright position. The significance is maintained despite the stratification of the sample according to age; in non-smokers we found a negative relationship between 1-OHP and differential blood pressure, both systolic and diastolic., Conclusions: The results of the study suggest that occupational exposure to PAHs may be able to significantly influence the blood pressure probably acting on the autonomic nervous system.

Objective: Outdoor workers are daily exposed to urban pollutants. The aim of the study is to evaluate the relationship between the values of environmental monitoring collected by personal dosimetries and changes in blood pressure due to posture in outdoor workers., Materials and Methods: 32 subjects of both sexes were enrolled in the study, we evaluated the values of environmental monitoring of breathable dust, nickel, arsenic, cadmium, lead, benzene, toluene, xylene and 16 PAHs. Blood pressure in supine and standing positions was measured in all subjects., Results: The multiple linear regression analysis showed a significant reduction of orthostatic response of diastolic blood pressure in non-smoking outdoor workers occupationally exposed to cadmium., Conclusions: The results of our study let us to believe that exposure to low doses of urban polluted cadmium may affect the response of diastolic blood pressure to orthostatism, as per a paraphysiological condition of sympathetic down-regulation.

Cytochrome c undergoes structural variations during the apoptotic process; such changes have been related to modifications occurring in the protein when it forms a complex with cardiolipin, one of the phospholipids constituting the mitochondrial membrane. Although several studies have been performed to identify the site(s) of the protein involved in the cytochrome c-cardiolipin interaction, to date the location of this hosting region(s) remains unidentified and is a matter of debate. To gain deeper insight into the reaction mechanism, we investigate the role that the Lys72, Lys73, and Lys79 residues play in the cytochrome c-cardiolipin interaction, as these side chains appear to be critical for cytochrome c-cardiolipin recognition. The Lys72Asn, Lys73Asn, Lys79Asn, Lys72/73Asn, and Lys72/73/79Asn mutants of horse heart cytochrome c were produced and characterized by circular dichroism, ultraviolet-visible, and resonance Raman spectroscopies, and the effects of the mutations on the interaction of the variants with cardiolipin have been investigated. The mutants are characterized by a subpopulation with non-native axial coordination and are less stable than the wild-type protein. Furthermore, the mutants lacking Lys72 and/or Lys79 do not bind cardiolipin, and those lacking Lys73, although they form a complex with the phospholipid, do not show any peroxidase activity. These observations indicate that the Lys72, Lys73, and Lys79 residues stabilize the native axial Met80-Fe(III) coordination as well as the tertiary structure of cytochrome c. Moreover, while Lys72 and Lys79 are critical for cytochrome c-cardiolipin recognition, the simultaneous presence of Lys72, Lys73, and Lys79 is necessary for the peroxidase activity of cardiolipin-bound cytochrome c.

Objective: To assess the risk factors for upper extremity-work-related musculoskeletal disorders (UE-WMSD) on 13 production lines in an airbag factory using the threshold limit values-American conference of industrial hygienists- hand activity level (TLV-ACGIH-HAL) method and introduce the ergonomic improvement to reduce the repetitiveness and the peak force (Pf)., Methods: Professional exposure level on 13 production lines in a automobile factory was measured using the TLV-ACGIH-HAL method and a further risk was assessed according to the ergonomic improvement., Results: The first assessment of 9 production lines showed that the professional exposure level was above the TLV or HAL limit. The second assessment showed that the professional exposure level was below the AL limit on all production lines except 1, in which the professional exposure level was between TLV and HAL., Conclusion: The assessment of UE-WMSD-related risk can identify the riskiest emplacements and evaluate the reduction of risk in professional exposure through interventions of structural- organizational type., (Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Urban pollution is a current problem, constituting a serious health risk. Many pollutants are present in the urban atmosphere, they are mainly anthropogenic, resulting from the combustion of coal. Several studies have shown the harmful effects of these pollutants, particularly on the respiratory system. Through a library review, we want to explore the effects on the health of general population and of outdoor workers exposed to the products resulting from the combustion of coal, in order to compare them with the estimated effects of the pollutants from the new generation coal plants, certainly less harmful to the environment. In recent years investments in "clean technologies" have resulted in a rapid and significant reduction of all polluting emissions: sulfur dioxide, dust, oxides of nitrogen, ash and gypsum resulting from the desulfurization process. To conclude in the light of the scientific literature we can say that the activation of coal plants based on technologies for the maximum containment and optimal treatment of the production cycle is essential to defend both the environment and the health of the population. Nevertheless it remains necessary to ensure a systematic monitoring of the environment of sanitation and food processing of the population living in the area, with a long-term follow-up.

The new D. Lgs. N 81, 2008 Article 28 paragraph 1 sanctions that the risk assessment must involve all the possible risks to safety and health of workers, including the work-related stress factors. Stressors at work may vary as to: quantity of work assigned, whether excessive or inadequate; lack of recognition or reward for good job performance; degree of responsibility; precariousness of work; emotional pressures exerted on workers; violence and harassment of psychological nature, poor balance between work and private life. The need man has to understand the causes of his psycho-physical and social disease are old. Only the words we use when dealing with the topic has changed over the time: once it was Alienation now it is Burn-out. The concept of alienation, which has been very important over the time, has many different aspects and has had countless interpretations (which have followed one another), the psycho-analytical, the sociological analysis and the Marxist one, Burnout is actually a syndrome characterized by three interrelated dimensions: exhaustion, cynicism and inefficacy. Therefore it is important to prevent, eliminate or reduce problems related to occupational stress. Among preventive measures, the Europe Agreement identified in the management and in the communication the information necessary to define the goals of the company and the role each employee has. Moreover information and formation are considered the necessary elements to increase awareness and understanding of the problem, its potential causes and possible ways of approading it. Our research group, has developed targeted questionnaires, biological indicators and medical instrumental examinations the occupational doctors can make use of to assess these issues.

Background: Purpose of this study is to evaluate and to compare the excretion of urinary 1-hydroxypyrene (1-OHPu) in traffic policemen (TP) and drivers (D) of a large Italian city and to evaluate the existence and the degree of correlation between airborne exposure to 15 different polycyclic aromatic hydrocarbons (PAHs) and 1-OHPu levels in the examined population., Methods: 192 male workers, 115 TP and 77 D, were monitored for 1-HOPu. A subgroup of non-smoking workers (subgroup B: 59 TP and 15 D) was also examined and 15 environmental PAHs was monitored through the personal samplings for the measurement of the particulate phase., Results: The 1-OHPu levels and the values of personal airborne exposure to PAHs were significantly higher among non-smoking TP than among non-smoking D (p < 0.05). In subgroup B the levels of environmental exposure to all the 15 PAHs measured in TP and only 6 of 15 PAHs measured in D were significantly correlated with the values of 1-OHPu (p < 0.05)., Conclusions: Our results suggest that the use of 1-OHPu as an indicator of exposure to PAHs is reliable also for what concerns the study of the low-dose work-related exposure in urban outdoor workers.

Background: Cadmium (Cd) is a metal, which induces hypertension in animals. This may not be relevant to the human population because the number of studies is inconsistent., Objective: Our aim is to identify an association between levels of blood/urinary cadmium and blood pressure in a group of employees of the municipal police assigned to outdoor activities., Materials and Methods: 349 subjects of both sexes were enrolled and sorted on the basis of gender, job function and smoking habit. Blood and urinary cadmium levels and blood pressure readings were collected for each subject. The data were subjected to statistical evaluation. Pearson correlation coefficient between the variables and a linear regression curve was drawn. After eliminating the confounding factors, the multiple linear regression analysis assessed statistical differences. Associations were considered significant at p < 0.05., Results and Conclusions: The Pearson correlation showed a positive association between urinary cadmium levels and blood pressure especially for groups of women and non-smokers. The simple and multiple linear regression and t-tests confirmed these associations and underlined the influence cadmium has on diastolic blood pressure, higher than systolic blood pressure. No association was found between blood cadmium and blood pressure. In conclusion, we can say that there is a statistically significant association between urinary cadmium and diastolic blood pressure, supporting the hypothesis that cadmium has a long-term effect on diastolic blood pressure (BP).