Clinical observation of extraction-site incisional hernia after laparoscopic colorectal surgery.

BACKGROUND: Laparoscopic colorectal cancer surgery increases the risk of incisional hernia (IH) at the tumor extraction site. AIM: To investigate the incidence of IH at extraction sites following laparoscopic colorectal cancer surgery and identify the risk factors for IH incidence. METHODS: This study retrospectively analyzed the data of 1614 patients who underwent laparoscopic radical colorectal cancer surgery with tumor extraction through the abdominal wall at our center between January 2017 and December 2022. Differences in the incidence of postoperative IH at different extraction sites and the risk factors for IH incidence were investigated. RESULTS: Among the 1614 patients who underwent laparoscopic radical colorectal cancer surgery, 303 (18.8%), 923 (57.2%), 171 (10.6%), and 217 (13.4%) tumors were extracted through supraumbilical midline, infraumbilical midline, umbilical, and off-midline incisions. Of these, 52 patients developed IH in the abdominal wall, with an incidence of 3.2%. The incidence of postoperative IH was significantly higher in the off-midline incision group (8.8%) than in the middle incision groups [the supraumbilical midline (2.6%), infraumbilical midline (2.2%), and umbilical incision (2.9%) groups] (χ2 = 24.985; P < 0.05). Univariate analysis showed that IH occurrence was associated with age, obesity, sex, chronic cough, incision infection, and combined diabetes, anemia, and hypoproteinemia (P < 0.05). Similarly, multivariate analysis showed that off-midline incision, age, sex (female), obesity, incision infection, combined chronic cough, and hypoproteinemia were independent risk factors for IH at the site of laparoscopic colorectal cancer surgery (P < 0.05). CONCLUSION: The incidence of postoperative IH differs between extraction sites for laparoscopic colorectal cancer surgery. The infraumbilical midline incision is associated with a lower hernia rate and is thus a suitable tumor extraction site.

Mortality due to respiratory system disease and lung cancer among female workers exposed to chrysotile in Eastern China: A cross-sectional study.

Female workers in the asbestos processing industry of Eastern China are at high risk of developing multiple types of cancer, and more data are urgently needed to better understand and address this issue. Death certificate data were selected from an asbestos processing city in China from 2005 to 2006. Information was investigated using the relatives of those individuals who had died as sources of information. Individuals were classified into one of three asbestos exposure levels. Standardized mortality ratio and 95% confidence interval were calculated. A total of 2,964 individual deaths were identified from 2005 to 2006; of these, 21.4% were occupationally exposed to asbestos. The main cause of death was circulatory system diseases (21.2%). The proportion of individuals with respiratory system diseases increased by age among each exposure subgroup (P trend < 0.01). Among females, a significant trend was observed between increased asbestos exposure and mortality due to respiratory system diseases and lung cancer. Our study indicated that asbestos exposure was associated with excess mortality from lung cancer and respiratory diseases, particularly among female workers in an asbestos processing area in Eastern China.

Overexpression of ADAM9 decreases radiosensitivity of hepatocellular carcinoma cell by activating autophagy.

A disintegrin and a metalloprotease (ADAM)9 upregulated within human hepatocellular carcinoma (HCC) cells, but its effect on HCC radiosensitivity remains unknown. The present work aimed to examine the effect of ADAM9 on HCC radiosensitivity and to reveal its possible mechanism, which may be helpful in identifying a potential therapeutic strategy. Changes in ADAM9 expression after X-ray irradiation were identified using western blot, qRT-PCR, and immunofluorescence. ADAM9 stable knockdown and overexpression cell lines were constructed using lentivirus packaging. The radiosensitivity of HCC cells with altered ADAM9 expression was examined by CCK-8 assays, subcutaneous tumorigenesis experiments, and clone formation assays. This study also determined how autophagy affected HCC cell radiosensitivity. Furthermore, ADAM9, p62 and Bax expressions in HCC tissues that were removed after radiotherapy were detected by immunohistochemistry, and the relationship among the levels of these molecules was statistically analyzed. The level of ADAM9expression in HCC cells increased after X-ray irradiation. Through CCK-8 assays, subcutaneous tumorigenesis experiments, and clone formation assays, this work discovered the increased MHCC97H cell radiosensitivity after ADAM9 knockdown, and the radiosensitivity of Huh7 cells decreased after the overexpression of ADAM9. Furthermore, ADAM9 induced HCC cell autophagy via downregulating Nrf2 expression, while autophagy inhibition or induction reversed the effects of altered ADAM9 expression on radiosensitivity. Moreover, ADAM9 level showed a negative correlation with Bax and p62 expression within HCC tissues after radiotherapy. Taken together, ADAM9 decreased the radiosensitivity of HCC cells, and autophagy mediated this process.

miR221 regulates cell migration by targeting annexin a1 expression in human mesothelial MeT-5A cells neoplastic-like transformed by multi-walled carbon nanotube.

BACKGROUND: Multi-walled carbon nanotube (MWCNT) is one of the most widely used manufactured nanomaterials, however, its potential harmful effect on human health is of great concern. Previously we have shown the acute and chronic exposure to MWCNT induced different responses in human mesothelial MeT-5A cells. In the current study, MeT-5A cells were continuously subjected to MWCNT exposure at 10 µg/cm2 for 48 h per passage, up to a whole year, to further clarify the carcinogesis and its potential mechanisms of MWCNT. RESULTS: After one-year MWCNT treatment, MeT-5A cells exhibited neoplastic-like properties, including morphological changes, anchorage-independent growth, increased cell proliferation and cell migration. Further examination revealed the expression of microRNA 221 (miR221) was gradually decreased, while the annexin a1 expression was increased at both the mRNA and protein level during the exposure. Bioinformatic analysis indicated that annexin a1 is a target for miR221 regulation, and it was confirmed by transfecting cells with miR221 mimics, which resulted in the downregulation of annexin a1. Detailed analyses demonstrated miR221 was involved in the regulation of cell migration, e.g., downregulation of miR221 or overexpression of ANNEXIN A1, contributed to the increased cell migration. In contrast, overexpression of miR221 or downregulation of ANNEXIN A1 slowed cell migration. CONCLUSIONS: Taken together, these results point to a neoplastic-transforming property of MWCNT, and the miR221-annexin a1 axis is involved in the regulation of cell migration in the transformed cells.

lncRNA MEG3, Acting as a ceRNA, Modulates RPE Differentiation Through the miR-7-5p/Pax6 Axis.

Accumulated evidence indicated that long non-coding RNAs (lncRNAs) involves in numerous biological and pathological processes, including age-related macular degeneration (AMD). Dysfunction and dedifferentiation of retinal pigment epithelium (RPE) cells have been demonstrated to be one of the crucial factor in AMD etiology. Herein, we aim to investigate the essential role of lncRNA maternally expressed gene 3 (MEG3) in AMD progression. Expression patterns of MEG3 were measured in dysfunctional REP cells exposed with H2O2 or TNF-α using qRT-PCR assay. Specifically, the intercellular distribution of MEG3 in REP cells was further explored using the subcellular fraction detection. Relative expression of RPE markers or RPE dedifferentiation-related markers was determined using qRT-PCR and western blot analysis, respectively. Immunofluorescence staining was performed to examine the expressions of RPE markers ZO-1 and ß-catenin. Concentration of vascular endothelial growth factor (VEGFA) in the supernatant was detected using ELISA kit. Luciferase reporter assay was performed to verify the MEG3/miR-7-5p/Pax6 regulatory network, which was further determined in in vitro studies. MEG3 expression was significantly decreased in H2O2 or TNF-α-treated REP cells, and it was upregulated along with RPE differentiation. Reduced MEG3 expression resulted in RPE dedifferentiation, which was indicated by decreased expressions of RPE markers, accumulated mitochondrial reactive oxygen species, and reduced VEGFA. Mechanistically, MEG3 functioned as a sponge for miR-7-5p to restore the expression of Pax6. Our study demonstrated that MEG3 exerts a protective role against AMD by maintaining RPE differentiation via miR-7-5p/Pax6 axis, suggesting a protective therapeutic target in AMD treatment.

A nontoxic dose of chrysotile can malignantly transform Met-5A cells, in which microRNA-28 has inhibitory effects.

Chrysotile, which is classified as a class I carcinogen by the International Agency for Research on Cancer (IARC), has extensive application in the industry and can lead to lung or other cancers. However, whether chrysotile causes malignant mesothelioma and its molecular mechanism remain debatable. Thus, this study aimed to demonstrate the mesothelioma-inducing potential of chrysotile at the mesothelial cellular level and the function of microRNA-28 in malignantly transformed mesothelial MeT-5A cells. MeT-5A cells malignantly transformed by a nontoxic dose of chrysotile were named Asb-T, and miR-28 expression was downregulated in Asb-T cells. Restoration of miR-28 expression inhibited the proliferation, migration and invasion of Asb-T cells. We verified that IMPDH is a putative target of miR-28. The expression of IMPDH was significantly higher in Asb-T MeT-5A cells than in control cells, whereas the opposite trend was observed with miR-28 overexpression. Additionally, inhibition of IMPDH had similar effects as miR-28 overexpression. After miR-28 was elevated or IMPDH was inhibited, Ras activation was reduced, and its downstream pathways (the Erk and Akt signalling pathways) were inhibited. Surprisingly, the content of miR-28 in the blood of mesothelioma patients was higher than that in control subjects. Overall, nontoxic doses of chrysotile can cause malignant transformation of MeT-5A cells. Moreover, miR-28 inhibits the proliferation, migration and invasion of Asb-T MeT-5A cells, negatively regulates the expression of IMPDH through the Ras signalling pathway and may be an important therapeutic target.

Role of PARP1 on DNA damage induced by mineral silicate chrysotile in bronchial epithelial and pleural mesothelial cells.

To investigate whether poly (ADP ribose) polymerase-1 (PARP1) is involved in chrysotile-induced DNA damage in pleural mesothelial cells (MeT-5A) and bronchial epithelial cells (BEAS-2B), two PARP1-deficient cell lines were established. Efficiencies of RNA interference on PARP1 were detected by western blot and qPCR. Here, normal cells and PARP1-deficient cells were exposed to chrysotile, and DNA damage and DNA repair were detected by alkaline comet assay. All cells were treated with chrysotile at the indicated concentrations (5, 10, 20, and 40 µg/cm2) for 24 h and then the DNA repair capacity was observed for 12 and 24 h, respectively. The results showed that chrysotile caused DNA damage at an obvious dose-dependent manner in MeT-5A and BEAS-2B cells. In addition, MeT-5A cells had more persistent DNA damage than BEAS-2B. Compared to normal cells, the PARP1-deficient cells were more sensitive to DNA damage caused by chrysotile. In DNA repair experiments, all cell lines recovered from the damage over time. The results of relative repair percentage (RRP) of MeT-5A and BEAS-2B were higher than those of MeT-5A shPARP1 and BEAS-2B shPARP1 cells at all experimental concentrations (except 5 µg/cm2) at 12-h repair. However, RRP of BEAS-2B and BEAS-2B shPARP1 tended to be closer, and RRP of MeT-5A shPARP1 was still lower than that of MeT-5A at 24-h repair. All results suggest that PARP1 plays an important role in early repair of DNA damage in BEAS-2B and MeT-5A cells exposed to chrysotile.

Cholinesterase homozygous genotype as susceptible biomarker of hypertriglyceridaemia for pesticide-exposed agricultural workers.

PURPOSE: Dyslipidemia is an emerging metabolic disorder among pesticide-exposed agricultural workers, and this study was aimed to explore biomarkers of hypertriglyceridaemia susceptibility. METHODS: This cross-sectional study recruited 72 pesticide-exposed subjects and 78 non-exposed controls. Lipid profile, cholinesterase activity, and thyroid hormones were analysed with routine assays. Six loci, including rs11206244 and rs2235544 for deiodinase 1, rs12885300 and rs225014 for deiodinase 2, rs1803274 for butyrylcholinesterase, and rs3757869 for acetylcholinesterase were genotyped using an improved multiplex ligation detection reaction technique. RESULTS: Pesticide-exposed subjects showed higher levels of triglyceride than controls (p = 0.009), although there were comparable cholinesterase activity and genotype frequencies of all six loci between pesticide-exposed subjects and controls. Pesticide-exposed subjects with homozygous genotype of cholinesterase had increased triglyceride levels than controls (p < 0.05). The percentage of hypertriglyceridaemia was 28.6% and 8.8% for pesticide-exposed subjects and controls with homozygous butyrylcholinesterase genotype (p = 0.007) and 20.8% and 14.3% with homozygous acetylcholinesterase genotype (p = 0.792), respectively. Multivariate logistic regression analyses found that odds ratio of hypertriglyceridaemia is 21.92 and 4.56 for pesticide-exposed subjects with homozygous genotype of butyrylcholinesterase (p = 0.001) and acetylcholinesterase (p = 0.036), respectively. CONCLUSIONS: Cholinesterase homozygous genotype might be a potential susceptible biomarker in screening pesticide-exposed agricultural workers vulnerable to hypertriglyceridaemia.

Exploration of identifying novel serum biomarkers for malignant mesothelioma using iTRAQ combined with 2D-LC-MS/MS.

Malignant mesothelioma (MM) is an aggressive cancer linked to asbestos exposure. Its poor prognosis makes early diagnosis extremely important, which would provide an opportunity for early treatment and potentially changing outcomes. This study aimed to explore the underlying mechanisms of MM and discover novel noninvasive biomarkers for the diagnosis of malignant mesothelioma. Using Isobaric tags for relative and absolute quantitation (iTRAQ) combined with two-dimensional liquid chromatography/tandem mass spectrometry (2D LC-MS/MS), a total of 145 differentially expressed serum proteins were identified between MM patients and healthy controls. The identified proteins were further analyzed by bioinformatics, out of which three candidate biomarkers (Filamin A (FLNA), Fibulin 1 (FBLN1) and Thrombospondin-1 (TSP-1)) were validated in large cohorts of patients with asbestos-related diseases including MM patients by ELISA assay. Receiver operating characteristic (ROC) curve analysis showed that serum FLNA, FBLN1 and TSP-1 had high diagnostic values in distinguishing MM patients from healthy controls, individuals with asbestos exposure (AE), and patients with pleural plaques (PP) or asbestosis. Meanwhile, serum FBLN1 and TSP-1 possessed good diagnostic values in distinguishing asbestosis patients from healthy controls and individuals with AE. The combination of FLNA, FBLN1, and TSP-1 proteins had higher sensitivity and specificity in discriminating patients with MM, PP and asbestosis. Our findings indicated that analysis of serum proteome using iTRAQ is a feasible strategy for biomarker discovery, and serum FLNA, FBLN1 and TSP-1 may be promising candidates for diagnosis of malignant mesothelioma and screening of at-risk individuals.

Genome-wide profiling reveals novel microRNAs in hand-spinning-specific chrysotile exposure.

AIM: We aimed to explore miRNA expression profiles in hand-spinning chrysotile exposed workers and their potential influencing factors. METHODS: miRNA array technique was applied to screen differentially expressed miRNAs between plasma samples from three exposed workers and three controls. Then, seven selected miRNAs were validated in 143 workers and 100 controls, and the potential influencing factors were revealed by multiple linear regression. Finally, the expression levels of those seven miRNAs were evaluated in human mesothelial cells (Met-5A) that were exposed to chrysotile at 5 µg·cm-2 for 8, 24 and 48 h, respectively. RESULTS & CONCLUSION: Hand-spinning chrysotile exposure can result in differential expression of miRNAs. Several of those miRNAs have positive correlations with asbestos exposure.

N-acetylcysteine prevents cytotoxic effects induced by man-made mineral fibers in a human bronchial epithelial cell line.

Man-made mineral fibres (MMMFs) such as glass wool (GW), rock wool (RW) and refractory ceramic fibres (RCFs) are widely used as substitutes of asbestos. The present study aimed to investigate the cytotoxic effects on human bronchial epithelial cells (BEAS-2B) exposed to GW1, RW1 and RCF2, considering their properties similar to that of asbestos. We assessed cell viability; cell morphological changes; apoptotic rate; DNA damage; reactive oxygen species (ROS) generation; activities of caspase-3, caspase-8 and caspase-9; and expression levels of FasL, phosphorylated p38, and total p38 MAPK proteins. N-acetyl-l-cysteine (NAC) was used as an ROS scavenger. We observed that MMMFs, especially RCF2, evidently changed cellular morphology, promoted DNA damage, and induced apoptosis. In addition, the cytotoxicities of MMMFs were dependent on ROS generation, and NAC could decrease their toxicity. Furthermore, our results showed that apoptosis induced by MMMFs was mediated by the mitochondrial apoptotic pathway and Fas death receptor pathway. Moreover, the p38 MAPK signalling pathway was also involved in the cytotoxicities of MMMFs. NAC exerts a protective effect against apoptosis and DNA damage induced by GW1, RW1 and RCF2. This study provides important implications for understanding the potential toxic effects of GW1, RW1 and RCF2 exposure; it also indicates that NAC may prevent respiratory diseases induced by exposure to MMMFs.

Plasma Fibulin-3 as a Potential Biomarker for Patients with Asbestos-Related Diseases in the Han Population.

Fibulin-3 has been reported as a potential biomarker for mesothelioma. However, little is known about the diagnostic efficacies of fibulin-3 for asbestos-related diseases (ARDs) in China. This study was to investigate the utility of fibulin-3 for asbestos exposure and ARDs. A total of 430 subjects were recruited from Southeast China, including healthy individuals, asbestos-exposed (AE) individuals, and patients with pleural plaques (PP), asbestosis, and malignant pleural mesothelioma (MPM). Plasma fibulin-3 was measured using the enzyme-linked immunosorbent assay. Linear regression analyses were applied to explore the influencing factors of fibulin-3. Receiver operating characteristic curves were used to determine the cutoff values. The median fibulin-3 level of subjects in the mesothelioma group was higher than that in other groups. Subjects in the asbestosis group had higher median fibulin-3 level than those in the control group. A higher fibulin-3 level was found in the group with ≥10 years of asbestos exposure as compared with control groups. The AUCs of fibulin-3 for distinguishing MPM subjects from control, AE, PP, and asbestosis subjects were 0.92, 0.88, 0.90, and 0.81, respectively. Our study provided evidence that fibulin-3 could be a potential biomarker for the early screening of MPM, but not of other nonmalignant ARDs in Chinese populations.

miR-30d is related to asbestos exposure and inhibits migration and invasion in NCI-H2452 cells.

Pleural malignant mesothelioma (MM) is a highly aggressive tumor that is typically related to asbestos exposure and has a latency of 20-60 years. Several microRNA contribute to MM initiation and progression, but the mechanisms are not clear. Here, we found that miR-30d is downregulated in the pleural MM cell line NCI-H2452, in the plasma of asbestos-exposed individuals, and in asbestos-exposed mesothelial cells. Furthermore, we investigated the influence of the overexpression of miR-30d in pleural MM cells. We demonstrated that miR-30d overexpression could suppress pleural MM cell proliferation, migration, and invasion in vitro and could promote cell apoptosis but could not significantly influence cell cycle. The mRNA and protein expression of vimentin and TWIST1 decreased, and the mRNA expression of CDH1 increased in NCI-H2452 cells that overexpressed miR-30d. We therefore conclude that miR-30d is related to asbestos exposure and inhibits cell migration and invasion by regulating the epithelial-mesenchymal transition in NCI-H2452 cells.

Different Cellular Response of Human Mesothelial Cell MeT-5A to Short-Term and Long-Term Multiwalled Carbon Nanotubes Exposure.

Despite being a commercially important product, multiwalled carbon nanotubes (MWCNTs) continue to raise concerns over human health due to their structural similarity to asbestos. Indeed, exposure to MWCNT has been shown to induce lung cancer and even mesothelioma, but contradictory results also exist. To clarify the potentially carcinogenic effects of rigid and rod-like MWCNT and to elucidate the underlying mechanisms, the effects of MWCNT on human mesothelial cell MeT-5A were examined throughout 3 months of continuous exposure, including cytotoxicity, genotoxicity, and cell motility. It was found that MWCNT did not affect MeT-5A cell proliferation at 10 µg/cm2 within 72 h treatment, but under the same condition, MWCNT induced genotoxicity and perturbed cell motility. In addition, MeT-5A cells demonstrated different cellular responses to MWCNT after short-term and long-term exposure. Taken together, our results indicated a possible carcinogenic potential for MWCNT after long-term treatment, in which Annexin family proteins might be involved.

Chrysotile Causes Human Bronchial Epithelial Cell Apoptosis in Response to the Fas-Mediated Apoptosis Pathway.

AIMS: Asbestos is harmful to human health. However, the pathogenicity of chrysotile is a controversial matter. This study aimed to investigate the apoptosis of a human bronchial epithelial cell line (BEAS-2B) exposed to chrysotile that may function in part through the Fas death receptor pathway. METHODS: Cultured human BEAS-2B cells were treated with chrysotile and cell viability was evaluated by CCK-8 assay. The induction of cell apoptosis was evaluated by FACS analysis. mRNA expression levels of Fas, caspase-3, and caspase-8 were evaluated quantitatively by real-time PCR. The expression of Fas, caspase-3, and caspase-8 proteins were evaluated by Western blot. Meanwhile, cells were preincubated with various concentrations of anti-Fas antibody (CH11) and antagonistic anti-Fas antibody (ZB4). RESULTS: Chrysotile inhibits proliferation, induces apoptosis, and upregulates the expression of Fas, caspase-3, and caspase-8. The role of Fas as a regulator of chrysotile-induced apoptosis in BEAS-2B cells was tested by the prominent increase in and partial blockade of the apoptotic rate with CH11 and ZB4. When CH11 was pretreated, a synergistic effect was apparent on chrysotile-induced apoptosis and the mRNA and protein expression levels of Fas and cleaved caspase-3. CONCLUSION: Chrysotile causes the apoptosis of BEAS-2B cells via the Fas death receptor pathway. The Fas-mediated apoptosis pathway plays an important role in chrysotile-induced apoptosis of BEAS-2B cells in vitro.

Serum HMGB1 as a Potential Biomarker for Patients with Asbestos-Related Diseases.

High-mobility group box 1 (HMGB1) functions as a proinflammatory cytokine and is one of the most intriguing molecules in inflammatory disorders and cancers. Notably, HMGB1 is a potential therapeutic target and novel biomarker in related diseases. However, the diagnostic value of HMGB1 for benign and malignant asbestos-related diseases (ARDs) remains unclear. In this work, we detected preoperative serum HMGB1 levels in Chinese asbestos-exposed (AE) and ARDs populations and further evaluated the diagnostic value of HMGB1 in patients with certain types of ARDs, including those with pleural plaques, asbestosis, or malignant mesothelioma (MM). The experimental data presented that the serum level of HMGB1 was significantly elevated in AE and ARDs subjects. Our findings indicated that serum HMGB1 is a sensitive and specific biomarker for discriminating asbestosis- and MM-affected individuals from healthy or AE individuals. In addition, serum matrix metalloproteinases 2 and 9 are not correlated with HMGB1 in ARDs. Thus, our study provides supporting evidence for HMGB1 as a potential biomarker either for the clinical diagnosis of high-risk AE cohorts or for evaluating ARDs.

Global DNA hypomethylation has no impact on lung function or serum inflammatory and fibrosis cytokines in asbestos-exposed population.

PURPOSE: To examine the effect of asbestos exposure on global DNA methylation and determine whether lung function and inflammatory and fibrosis biomarkers are correlated with the methylation state. METHODS: A total of 26 healthy subjects without asbestos exposure (Group 1), 47 healthy subjects with exposure (Group 2), and 52 subjects with benign asbestos-related disorders (ARDs) (Group 3) participated in this cross-sectional study. Blood global 5-methylcytosine (5mC) and serum TNF-α, collagen IV, CCL5 and CC16 concentrations were analyzed using enzyme-linked immunosorbent assay-like assays. Spirometric maneuvers were performed to assess lung function. RESULTS: Decreased 5mC levels were observed in Groups 2 and 3 compared to Group 1, irrespective of lung function (p < 0.01). There was no significant change in 5mC between Groups 2 and 3. Overall, 5mC was negatively correlated with CCL5 and collagen IV (p < 0.05), but no significant inverse relationship was found between 5mC and CCL5 or collagen IV in each group. Additionally, both 5mC and CC16 were inversely associated with FEV1/FVC% (p = 0.001, adjusted R 2 = 0.145) for non-smokers, and consistently significant inverse relationships were found between CC16 and FEV1/FVC%, independent of asbestos exposure. CONCLUSIONS: Asbestos exposure causes global DNA hypomethylation. DNA hypomethylation has no influence on serum biomarkers and lung function in asbestos-exposed population with or without pleural and pulmonary parenchymal abnormalities.

Proteome Changes of Human Bone Marrow Mesenchymal Stem Cells Induced by 1,4-Benzoquinone.

Benzene is metabolized to hydroquinone in liver and subsequently transported to bone marrow for further oxidization to 1,4-benzoquinone (1,4-BQ), which may be related to the leukemia and other blood disorders. In the present study, we investigated the proteome profiles of human primary bone marrow mesenchymal stem cells (hBM-MSCs) treated by 1,4-BQ. We identified 32 proteins that were differentially expressed. Two of them, HSP27 and Vimentin, were verified at both mRNA and protein levels and their cellular localization was examined by immunofluorescence. We also found increased mRNA level of RAP1GDS1, a critical factor of metabolism that has been identified as a fusion partner in various hematopoietic malignancies. Therefore, these differentially expressed proteins can play important roles in benzene-mediated hematoxicity.

[Study on the therapeutic effects of tetrandrine combined with N-acetylcysteine on experimental silicosis of rats].

OBJECTIVE: To compare the effects of oral treatment with tetrandrine (TD) and N-acetylcys-teine (NAC) separately or jointly on silica-exposed rats. METHODS: 40 sprague-Dawly (SD) rats were randomly divided into normal saline group, quartz group, TD treatment group (50 mg/kg), NAC treatment group (500 mg/kg) and combined treatment group (TD: 50 mg/kg + NAC: 500 mg/kg). Rats in normal saline group and other groups received intratracheal instillation of normal saline and quartz dust suspension respectively. Treatment groups were given TD, NAC separately or jointly via esophagus the next day after instillation, once a day and six times a week for 30 consecutive days. At the end of experiment, the pathological changes of lung tissues were evaluated by the methods of Foot, HE and Masson staining, the level of hydroxyproline (HYP), malondjalde-hyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in lung tissues were measured by alkaline hydrolysis method, the barbituric acid method and enzyme-linked immunosorbent assay (ELISA) respectively. RESULTS: Compared with the quartz group, lymph nodes/body coefficients in all treatment groups and lung/body coefficient in combined treatment group were significantly decreased (P < 0.05). Pathology results showed that the normal saline group demonstrated no obvious evidence of lung damage. The quartz group lungs silicotic lesions focused on II~III level, the TD treatment group was mainly with I level, the NAC treatment group was mainly with I~II level, and the combined treatment group only showed little silicotic nodule, no obvious fibrosis. HYP content in TD treatment group and combined treatment group were significantly lower than that in the quartz group (P < 0.05), while it showed no obvious change in NAC treatment group. MDA content in lung tissues of each treatment group (TD treatment group, NAC treatment group and combined treatment group) were 18.80 ± 2.94, 20.13 ± 4.01 and 17.05 ± 3.52 nmol/ml respectively, which lower than in the quartz group (23.99 ± 3.26 nmol/ml). The level of IL-6 in lung tissues of the quartz group were 89.57 ± 8.78 pg/ml. After TD and NAC monotherapy, the IL-6 content decreased to 79.22 ± 9.65 pg/ml and 81.63 ± 5.72 pg/ml, and it decreased more significantly after combined medication (74.37 ± 3.17 pg/ml). The level of TNF-α in the quartz group were 59.05 ± 4.48 pg/ml. After TD and NAC monotherapy, the TNF-α content decreased to 50.48 ± 2.76 pg/ml and 54.28 ± 4.30 pg/ml, and it decreased more significantly after combined medication (49.10 ± 4.98 pg/ml). CONCLUSION: NAC and TD could reduce MDA, TNF-α and IL-6 levels in lung tissue, and alleviate SiO2-induced pulmonary fibrosis in rats. Combined treatment with TD and NAC was more effective than TD or NAC treatment separately.