ABSTRACT
Pneumoconiosis is the most common and severe occupational disease, has become a major public health problem in the world. Its causes are well known, but the pathogenesis of it is not completely clear and effective therapies are not currently available. Epigenetic modifications have been considered an initial event in the development of pneumoconiosis. Epigenetic regulatory mechanisms in pneumoconiosis include DNA methylation, non-coding RNA (ncRNA) , and histone modification. In recent years, many researchers have studied the effect of dust-induced pulmonary fibrosis-related gene expression at the epigenetic level on macrophage activation, lung fibroblast proliferation, activation, transdifferentiation, and epithelial or endothelial-mesenchymal transition (EMT/EndMT) to further elucidate the pathogenesis of pneumoconiosis. In this review, we discusses the epigenetic modifications in pneumoconiosis, with an aim to provide new insights into the early diagnosis, condition assessment and targeted therapy of this occupational disease.
ABSTRACT
OBJECTIVE: To investigate the application value of computed tomograph( CT) guided percutaneous lung biopsy in the diagnosis of occupational pneumoconiosis( the following is referred to as “pneumoconiosis”). METHODS: A total of63 cases of CT-guided percutaneous lung puncture biopsy from patients with pneumoconiosis,were analyzed for the successful rate of percutaneous lung puncture,the positive rate of pneumoconiosis pathological results and diagnostic accuracy. RESULTS: The successful rate of puncture was 100. 0% in these 63 cases. Pathological examination revealed60 cases of pneumoconiosis like change,with a positive rate of 95. 2%. Among them,56 cases were diffuse fibrosis,48 cases were dust deposition,and 32 cases were dusty nodules. There were 5 cases of tuberculosis granuloma,1 case of tumor,1 case of macrophage pneumonia and 1 case of infection. According to the pathological examination results,54 cases of simple pneumoconiosis,1 case of occupational hard metal lung disease,1 case of pneumoconiosis combined with tumor,4 cases of pneumoconiosis combined with tuberculosis and 2 cases of simple tuberculosis were confirmed. The diagnostic accuracy was 98. 4%. CONCLUSION: CT guided percutaneous lung biopsy is an ideal clinical method for obtaining pathological specimens of lung tissue. The positive rate of detecting pneumoconiosis pathological changes is high.The accuracy of pneumoconiosis diagnosis is high. It has high application value in the diagnosis and differential diagnosis of pneumoconiosis.
ABSTRACT
In recent years, researches on cells, animals, and human beings have found that the carcinogenic mechanism of environmental carcinogen benzo (a) pyrene〔B(a)P〕can reduce methyla?tion of the whole genes, increase the tumor suppressor gene methylation and reduce the gene methyla?tion of proto-oncogene, in addition to the genetic toxicity. It can also cause changes in small RNA expression, the increase of long-chain non-coded RNA expression and imbalance in histone phosphor?ylation expressions. These changes can cause abnormalities in gene expression and chromosome structure and instability, directly leading to cancer. These changes can also cause the corresponding changes of genetic toxicity, such as gene mutation, abnormal genetic damage repair, increas of cell apoptosis and cell cycle arrest. All these are considered to be potential epigenetic mechanisms of B(a)P. Existing researches have provided the scientific basis for the mechanism of and prevention counter?measures for environment-related diseases and vocational diseases caused by B(a)P.
ABSTRACT
DNA methylation is part of the epigenetic modification process,which can lead to aberrant gene expression. Cytochrome P450 enzyme,cyclooxygenase,lipoxygenase and monoamine oxidase are a class of enzymes produced by human tissues,which are involved in the oxidization pro?cess of endogenous and exogenous chemicals. The methylation patterns of these enzyme genes are dif?ferent between normal tissues and pathological ones. Abnormal methylation patterns will change en?zymes′expression and function,and affect the occurrence and development of diseases. This paper re?viewed the characteristic changes of four oxidative metabolic enzyme genes in certain diseased tis?sues,the impact on methylation status of the metabolic activity of chemicals and on human health. It is hoped that this review can provide a new theoretical basis for the study on the toxic mechanism of chemicals and for diagnosis of diseases.
ABSTRACT
There is a close relationship between oxidative stress induced tissue damage and many diseases.As a multi-function oxidase,lipoxygenase can generate reactive oxygen species (ROS)by oxidatively metabolizing various endogenous and exogenous chemicals such as drugs and environmental pollutants.Lipoxygense can catalyze endogenous che mical reaction,such as arachidonic acid and pro-duce ROS.Lipoxygenase can be also activated in other ways to generate ROS by activating signal trans-duction.Moreover,some exogenous chemicals can be metabolized into highly reactive radical intermedi-ates by lipoxygenase,inducing ROS generation.The accumulation of intracellar ROS can damage intra-cellar redox balance and induce oxidative stress.That may be one of the possible toxic effect mecha-nis ms of che mical agents.
ABSTRACT
Lipoxygenase(LOX) is related to emergence and development of many diseases, such as acute and chronic inflammation, atherosclerosis, hypertension and tumor. Therefore, the inhibition of LOX may play an important role in the prevention and treatment of these diseases. Many kinds of flavonoids, such as chalcones, flavonols, flavones and flavanols, have inhibitory effect on 5-LOX, 12-LOX and 15-LOX probably through inhibiting expression of LOX, bonding to the enzyme or reacting with free radicals generated at the active site of the enzyme. Their inhibitory activities are related to their structures. The inhibitory effects of flavonoids on LOX maybe one of mechanisms of flavonoids' some biological functions, such as anti-inflammatory, anti-tumor and reducing the risk of cardiovascular disease and cerebrovascular disease.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the integrative quantitative index of the extent of pneumoconiotic changes by dusts and to evaluate the extent of pulmonary injury by the dusts containing different contents of free silica.</p><p><b>METHODS</b>In accordance with the morphometric principle, the areas of each kind of pathologic changes in the lung tissue sections of pneumoconiosis model were measured by utilizing a computer-aided graphic analyzer, and the volume density of each pathologic change and the value of pulmonary injury by dust(VPID) were calculated. Meanwhile the extent of pulmonary injury were compared among the rat groups treated with the dusts containing different contents of free silica.</p><p><b>RESULTS</b>There were significant differences among each groups in the volume density of some pathologic changes in the same exposed periods. There were significant correlation between VPID and the content of free silica dust or the lung collagen content (r = 0.535-0.849, P < 0.005 or P < 0.01). Furthermore, the degree of cor relationship of VPID with both of the latter were higher than the sum of unweighted volume density of the various pathologic changes in lung.</p><p><b>CONCLUSION</b>It is suitable, reasonable and simple to use VPID an index to indicate the extent of pulmonary injury by dust and to diagnose pneumoconiosis in pathology, and the extent of pulmonary injury by dust may be aggravated with the increasing of the content of free silica.</p>
Subject(s)
Animals , Rats , Dust , Lung , Pathology , Pneumoconiosis , Pathology , Silicon Dioxide , ToxicityABSTRACT
<p><b>OBJECTIVE</b>In order to explore the pathway of dealkylation of pesticides other than cytochrome P450 monocoxygenases, lipoxygenase (LOX)-mediated demethylation of aminocarb and some other pesticides were measured.</p><p><b>METHOD</b>Formaldehyde generated in the reaction was estimated by Nash reaction to express the rate of demethylation of pesticides mediated by soy lipoxygenase (SLO).</p><p><b>RESULTS</b>N-demethylation of aminocarb mediated by SLO was found to depend on the incubation time, concentration of the enzyme, concentration of aminocarb and hydrogen peroxide. Under optimal conditions, Vmax value of 18 nmol of formaldehyde.min-1.nmol-1 of lipoxygenase was observed. The reaction exhibited Km values of 3.4 mmol/L for aminocarb and 235 mumol/L for hydrogen peroxide. A strong inhibition of the reaction by nordihydroguaiaretic acid, gossypol, and phenidone clearly implicated the lipoxygenase involvement as the protein catalyst. A significant decline in the formaldehyde accumulation in the presence of either reduced glutathione or dithiothreitol suggested generation of a free radical species as an initial oxidation intermediate during the demethylation of aminocarb by SLO. The inhibition of formaldehyde generation by butylated hydroxyanisole(BHT) and butylated hydroxy toluene(BHA) further supported this contention. In addition to aminocarb, seven other pesticides were also found to undergo N-demethylation, albeit at relatively low rates.</p><p><b>CONCLUSION</b>Certain pesticides may oxidatively undergo dealkylation via the lipoxygenase pathway in animals and plants.</p>