[Study on the fit testing for the workers wearing hearing protection device in machinery manufacturing enterprises].

Objective: To investigate the occupational noise hazards in five machinery manufacturing enterprises, and to evaluate the individual noise reduction values and influencing factors of workers wearing hearing protection device (HPD) by individual fit testing. Methods: From November 2021 to January 2022, 5 machinery manufacturing enterprises in Bao'an District of Shenzhen were selected to conduct an occupational health survey to understand the noise exposure level of workers. The 3MTM E-A-RfitTM fitness test system was used to test the baseline individual sound attenuation value level (PAR) of the daily wear of the ear protecters for 485 workers in typical noise working positions. Workers whose PAR values could not meet the requirements of noise reduction at work were instructed to wear and repeated tests were conducted. PAR results of the workers before and after the intervention were collected and analyzed. Results: The noise workers who received the suitability test were mainly distributed in 24 types of work, the job noise exposure level was 80.2 dB (A) ~ 95.0 dB (A), and the job noise excess rate was 52.5% (138/263). The median baseline PAR [M (Q(1), Q(3)) ] for 485 workers was 6.0 (0.0, 14.0) dB. The baseline PAR of male workers, those with more than 15 years of working experience, those with more than 15 years of using ear guards, those who considered ear guards comfortable to wear, those with college degree or above, and those exposed to noise level 90 dB (A) were higher, and the difference was statistically significant (P<0.05). A total of 275 workers (56.7%) did not pass the baseline PAR test, and there was no statistically significant difference in the intervention rate of workers in different noise groups (P>0.05). PAR in subjects who did not pass baseline after intervention increased from 0.0 (0.0, 3.0) dB to 15.0 (12.0, 18.2) dB. Conclusion: The workplace noise hazard of machinery manufacturing enterprises is serious, and there is a great difference between the baseline PAR and the nominal value of the hearing guard worn by the noise exposed workers. The intervention measures can effectively improve the protective effect of wearing ear protectors.

[Research on the protective effect of hearing protective device for workers exposed to noise in a motor manufacturing enterprise].

Objective: To understand the current situation of noise hazard in a motor manufacturing enterprise, and to explore the protective effect of workers wearing hearing protective device and its possible influencing factors. Methods: In November 2021, a total of 179 noise workers wearing hearing protective devices in a motor manufacturing company in a city were selected as research objects. Personal attenuation rating (PAR) of workers wearing hearing protective devices was measured. Baseline PAR was analyzed for different subgroups of basic demographic information, noise exposure, and the use of hearing protective devices to evaluate the effect of the intervention. Baseline PAR was compared using nonparametric tests. Results: There were 179 workers from 35 positions in 4 types of work, and the over-standard noise rate was 51.2% (42/82), among which the noise exposure intensity of motor equipment debugging workers was the highest [94.4 dB (A) ]. Compared the baseline PAR of different characteristics, it was found that the baseline PAR of male workers, workers whose daily noise exposure time were <8 h, workers who had used the hearing protective devices for 10 to 14 years, and workers who thought the hearing protective devices were comfortable were all higher, and the differences were statistically significant (P<0.05). Baseline PAR passing rate was 43.0% (77/179), and PAR of 102 workers who did not pass baseline test increased from 0 (0, 3) dB before intervention to 14 (12, 16) dB after intervention, with statistical significance (P<0.05) . Conclusion: The noise hazard in this motor manufacturing enterprise is serious, and the protective effect of workers wearing hearing protective devices is not good. Gender, daily noise exposure time, years and comfort of wearing hearing protective device are the possible influencing factors of poor protective effect.

[Analysis of verification results of protective effects of hearing protectors in different industries].

Objective: To get insight into the current practice of noise reduction effect of workers as they wore hearing protectors in different domestic enterprises and the possible affected factors. Methods: From October 2020 to April 2021, using a random sampling method, 1197 workers exposed to noise in petrochemical factories, textile factories, and parts manufacturing factories were selected as the study subjects. The noise reduction effect of hearing protectors worn by workers in daily use was tested using a hearing protector suitability testing system. The personal sound attenuation level (PAR) was compared among workers in three enterprises, Targeted intervention and repetitive testing were conducted for workers who did not meet the noise reduction effect required by the enterprise, and the changes in PAR of workers before and after the intervention were compared. The comparison of baseline PARs between two or more groups was performed using the Mann Whitney test, the comparison of baseline PARs with post intervention PARs was performed using the Wilcoxon signed rank sum test, and the comparison of qualitative data between two or more groups was performed using the Chi square test. Results: The median baseline PAR for all workers was 15 dB. Men, age<30 years old, education level at or above college level, working experience of 5 to 15 years, and those who used hearing protectors for 5 to 15 years had higher PARs, with statistically significant differences (P<0.05). The median difference in baseline PAR among workers from three enterprises was statistically significant (H=175.06, P<0.01). The median PAR of subjects who did not pass the baseline increased from 3 dB to 21 dB after intervention (Z=-27.92, P<0.01) . Conclusion: Some workers wearing hearing protectors do not meet the required PAR, and low PARs may be related to incorrect wearing methods and incorrect selection of hearing protectors. As a tool for testing, training, and assisting in selection, the hearing protector suitability testing system is of great significance for worker hearing protection.

[Quantitative risk assessment of occupational exposure to PCDD/Fs in the waste incineration industry].

Objective: To analyze the level of PCDD/Fs exposure of occupational workers in the waste incineration industry and explore the risk of occupational exposure. Methods: In September 2021, literature on environmental PCDD/Fs exposure in waste incineration plants published from the establishment of the database to February 10, 2021 was retrieved from CNKI database. A total of 1365 literatures were retrieved, and 7 met the criteria for inclusion. The US Environmental Protection Agency (EPA) inhalation risk model was used to assess and analyze carcinogenic and non-carcinogenic risks of PCDD/Fs exposure among occupational workers in the waste incineration industry. Results: A total of 86 sampling sites were included in incineration plants in 7 regions. The study of Wuhan area showed that the concentration of working environment near the waste incinerator in the same factory was the highest, followed by the rest and office area in the factory. The concentration of PCDD/Fs in waste incinerators was the highest in Southwest China (4880.00-24880.00 pg TEQ/m(3)), and the lowest in Shenzhen (0.02-0.44 pg TEQ/m(3)). According to the cancer risk assessment, with the increase of exposure years, the risk of cancer increased. The highest risk of cancer was found in the waste incineration plants in Southwest China. When the exposure period was 1 year, the risk was moderate (22.40×10(-6)-114.20×10(-6)). When the exposure time was more than 5 years, the risk of cancer was high. In Jinan, workers working near the incinerator had a moderate risk of cancer after five years of exposure. In Zhejiang, workers were at medium risk of cancer after exposure for more than 20 years. Workers in Wuhan, Shanghai, Zhejiang Province, Shenzhen and the Pearl River Delta were still at low risk of cancer after 40 years of occupational exposure. HQ>1 of workers working near the waste incinerators in Jinan, Zhejiang Province and Southwest China, and the qualitative evaluation results showed that the non-carcinogenic risk was unacceptable. Conclusion: There are great differences in PCDD/Fs of occupational exposure in waste incineration industry, and the occupational exposure exceeding the occupational exposure limit has higher carcinogenic and non carcinogenic risks.

[Risk assessment on noise-induced hearing loss of 488 workers in a petrochemical plant].

Objective: To assess the risk of noise-induced hearing loss in workers from a petrochemical plant. Methods: In October 2020, 488 male workers exposed to noise in a petrochemical plant in Guangdong Province were selected by cluster sampling. Acoustics-Estimation of Noise-Induced Hearing Loss (ISO 1999: 2013) was used to assess the risk of noise-induced hearing loss of workers, and individual fit testing was used to evaluate the sound attenuation obtained by the workers. The risk assessment results and fitness test results of workers with different hearing levels were compared. Results: The average noise exposure equivalent sound level of the workers in the petrochemical plant was 86.7 dB (A) . The median of PARs (personal attenuation ratings) was 16 (4, 23) dB. There were statistically significant differences in age and service years among workers with different hearing results (P<0.05) , but no statistically significant differences in noise intensity and PARs (P>0.05) . According to risk assessment results of ISO 1999: 2013, the current risk of high-frequency hearing loss in 488 workers were negligible risk and acceptable risk. The risk of noise-induced deafness weredivided into three levels: negligible risk in 452 workers (92.7%) , medium risk in 27 workers (5.5%) and high risk in 9 workers (1.8%) . The risk of high-frequency hearing loss in next 5 to 15 years for workers with noise exposure level of >94 to 97 dB and >97 dB or above would be medium risk or above. The risk of noise-induced deafness in next 5 to 15 years for workers exposed to noise withlevel of 91 to 94 dB would be medium risk or above. Conclusion: The risk of noise-induced hearing loss in workers from the petrochemical plant is high in next 5 to 15 years, and noise prevention and control measures need to be strengthened. ISO1999: 2013 assessment method may underestimate the risk of hearing loss among workers.

[Application of multiple exposure assessment methods in occupational health risk assessment of trichloroethylene in electroplating enterprises].

Objective: To explore the applicability of different exposure assessment methods in occupational health risk assessment of trichloroethylene (TCE) occupation posts in electroplating enterprise. Methods: In November 2018, the occupational health risk assessments are conducted in trichloroethylene (TCE) occupation posts of 6 metal plating enterprises in a street in Shenzhen by using the qualitative risk assessment, semi-quantitative risk assessment (including contact ratio method, contact index method and synthesis index method) and quantitative risk assessment method (including non-carcinogenic and carcinogenic risk assessment methods) , and the results of different methods are compared. Results: The results of qualitative assessment method are all level 4 (high risk) ; the results of contact ratio method show that the risk level is level 5 (very high risk) ; the results of contact index method and Synthesis index method show that the risk level is level 3 and level 4, 66.7% and 33.3% respectively; Non-carcinogenic risk assessment results show that TCE jobs are "unacceptable"; carcinogenic risk assessment results in carcinogenic inhalation excess risk of 50% each being "unacceptable" and "acceptable". The results of the six risk assessment methods showed that there were 3 "substantially consistent", 1 "partially consistent", and 2 "inconsistent" among the 6 companies. Conclusion: Synthesis index method and the carcinogenic risk assessment method are more suitable for occupational health risks of TCE occupation posts.

Prognostic and predictive values of CXCL10 in colorectal cancer.

BACKGROUND: The role of CXCL10 in progression and prognosis of colorectal cancer (CRC) has been studied for years, yet results remain controversial. AIM: This study aims to explore the relationship between CXCL10 and CRC progression and prognosis. METHODS: We evaluated plasma CXCL10 in CRC patients using ELISA. We also performed a meta-analysis of the associations between CXCL10 and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), relapse-free survival (RFS), and clinicopathological features. Finally, correlations between CXCL10 and methylation or immune infiltration were performed using TCGA data. RESULTS: ELISA analysis showed that CXCL10 was associated with age, red blood cells, blood platelets, and blood urea nitrogen. A separate analysis of 3,763 patients from 24 studies revealed that there were significant associations between low CXCL10 expression and OS (HR 1.25, 95% CI 1.01-1.53), DFS (HR 1.65, 95% CI 1.17-2.34), and RFS (HR 1.43, 95% CI 1.20-1.71) in CRC. Additionally, downregulated CXCL10 expression was significantly correlated with age [odds ratio (OR) 1.31, 95% CI 1.13-1.52], metastasis (OR 1.34, 95% CI 1.11-1.63), recurrence (OR 1.46, 95% CI 1.16-1.83), tumor location (OR 1.88, 95% CI 1.58-2.24), differentiation (OR 0.57, 95% CI 0.35-0.93), microsatellite instability (OR 0.23, 95% CI 0.15-0.35), BRAF mutation (OR 1.62, 95% CI 1.25-2.08), p53 mutation (OR 0.28, 95% CI 0.16-0.47), and CIMP (OR 0.27, 95% CI 0.17-0.43). Furthermore, significant associations were observed between CXCL10 and methylation and immune infiltration. CONCLUSIONS: The study suggests that CXCL10 might be a potential target for the treatment of CRC. TRIAL REGISTRATION: NCT03189992. Registered 4 June 2017, https://www.clinicaltrials.gov/ct2/show/study/NCT03189992?term=NCT03189992&rank=1 .

[Application of three semi-quantitative risk assessment methods in electroplating enterprises].

Objective: To apply the semi-quantitative risk assessment model in the Technical Guidelines for Occupational Health Risk Assessment of Chemical Hazardous Factors in the Workplace to assess the occupational health risk of electroplating enterprises and explore its applicable conditions and characteristics. Methods: Three electroplating enterprises were selected as the research objects. Occupational hygiene survey and hazard factor detection were conducted on the spot. Three semi-quantitative risk assessment methods were used to assess the risk, and the evaluation results were compared. Results: The consistency between the contact index method and the comprehensive index method was strong. The weighted Kappa value was 0.946 and the P value was less than 0.001, but the consistency between the contact ratio method, the contact index method and the comprehensive index method was poor. The weighted Kappa value was 0.345 and 0.391, and the P value was 0.009 and 0.004, respectively. When the contact concentration is less than 50% OELs, the evaluation results of the contact ratio method are lower than those of the exponential method and the comprehensive exponential method. The consistency of the three methods was the highest when the contact concentration (>50%) and (OELs, the results of the contact ratio method are higher than those of the index method and the comprehensive index method. Conclusion: Contact ratio method is suitable for occupational health risk assessment under the condition of incomplete occupational health information and for enterprise managers to identify key control points of health risk through self-assessment; Contact index method is suitable for hazard risk assessment of occupational hazards without sampling test conditions or OELs, and pre-assessment of occupational hazards of construction projects without access to analogical test data. The index method is suitable for occupational health risk assessment with available testing data and complete occupational health information.

[Relationship between occupational stress, psychological capital and depressive symptoms among female workers in five electronic manufacturing enterprises].

Objective: To explore the relationship between occupational stress, psychological capital and depressive symptoms among electronic manufacturing female workers in the Pearl River Delta region. Methods: Using cluster sampling method, 845 female workers from 5 electronic manufacturing enterprises in the Pearl River Delta region were selected as research subjects from June to August 2017. The Effort Reward Imbalance questionnaire (ERI) , Psychological Capital questionnaire-24 (PCQ-24) and Patient Health questionnaire-9 (PHQ-9) were applied to measure the level of occupational stress, psychological capital and depressive symptoms in female workers. Results: Effort (r=0.197, P<0.01) and over commitment (r=-0.260, P<0.01) were positively correlated with the score of depressive symptoms, and the rewards was negatively correlated with depressive symptoms (r=-0.211, P<0.01) . The reward and over-commitment for depressive symptoms were accounted for 8.2%. Psychological capital was negatively correlated with depressive symptoms, and plays a partly mediating role in the relationship between occupational stress and depressive symptoms of female workers. The psychological capital for depressive symptoms was accounted for 8.7%. Conclusion: Occupational stress can affects the depressive symptoms of electronic manufacturing female workers, or indirectly affect depressive symptoms through psychological capital, reduce occupational stress and improve psychological capital as a way to relieve the depressive symptoms of female workers.

The Profile of Angiogenic Factors in Vitreous Humor of the Patients with Proliferative Diabetic Retinopathy.

OBJECTIVE: To explore the expression profile of angiogenic factors associated with proliferative diabetic retinopathy (PDR). METHODS: Undiluted vitreous humor samples were obtained from 10 diabetic patients with PDR (10 eyes) and 9 non-diabtic patients (9 eyes). The concentrations of 60 angiogenic factors in the vitreous humor samples were measured by RayBio Angiogenic Cytokine Antibody Array. Some differentially expressed factors were further confirmed in vitreous humor by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the non-diabetic controls, 20 differentially expressed factors with more than 1.50 fold changes were detected in patients with PDR. The median concentration of vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), angiopoietin (ANG)-1, ANG-2, urokinase-type plasminogen activator receptor (uPAR), Follistatin and matrix metalloproteinases 9 (MMP-9) was significantly increased in vitreous samples from PDR compared to controls (P < 0.05). However, (MCP)-1, Angiogenin and Leptin was significantly lower in PDR eyes compared to controls (P < 0.05). In the verification assay using ELISA, ANG-1, ANG-2, IL-6, VEGF, MMP-9, hepatocyte growth factor (HGF) and placenta growth factor (PIGF) concentration were increased in patients with PDR compared to controls (all P-values < 0.05). CONCLUSION: This is the first report of a comprehensive multiplex analysis to identify angiogenic factors associated with PDR. These angiogenic factors may contribute to the pathogenesis of PDR and may be targets for therapeutic strategies of PDR.

Epithelial-mesenchymal transition of ovarian cancer cells is sustained by Rac1 through simultaneous activation of MEK1/2 and Src signaling pathways.

Epithelial-mesenchymal transition (EMT) is regarded as a crucial contributing factor to cancer progression. Diverse factors have been identified as potent EMT inducers in ovarian cancer. However, molecular mechanism sustaining EMT of ovarian cancer cells remains elusive. Here we show that the presence of SOS1/EPS8/ABI1 complex is critical for sustained EMT traits of ovarian cancer cells. Consistent with the role of SOS1/EPS8/ABI1 complex as a Rac1-specific guanine nucleotide exchange factor, depleting Rac1 results in the loss of most of mesenchymal traits in mesenchymal-like ovarian cancer cells, whereas expressing constitutively active Rac1 leads to EMT in epithelial-like ovarian cancer cells. With the aid of clinically tested inhibitors targeting various EMT-associated signaling pathways, we show that only combined treatment of mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2) and Src inhibitors can abolish constitutively active Rac1-led EMT and mesenchymal traits displayed by mesenchymal-like ovarian cancer cells. Further experiments also reveal that EMT can be induced in epithelial-like ovarian cancer cells by co-expressing constitutively active MEK1 and Src rather than either alone. As the activities of Erk and Src are higher in ovarian cancer cells with constitutively active Rac1, we conclude that Rac1 sustains ovarian cancer cell EMT through simultaneous activation of MEK1/2 and Src signaling pathways. Importantly, we demonstrate that combined use of MEK1/2 and Src inhibitors effectively suppresses development of intraperitoneal xenografts and prolongs the survival of ovarian cancer-bearing mice. This study suggests that cocktail of MEK1/2 and Src inhibitors represents an effective therapeutic strategy against ovarian cancer progression.

Higher risk for thyroid diseases in physicians than in the general population: a Taiwan nationwide population-based secondary analysis study.

BACKGROUND: Physicians have high work stress, responsibility for night shifts and chances of exposure to medical radiation, which may increase the risk for thyroid diseases. AIM: We conducted this study to assess the risk for thyroid diseases in physicians, which remain unclear. DESIGN: We used a secondary analysis of the Taiwan National Health Insurance Research Database for this study. METHODS: After excluding thyroid diseases occurring before 2006 and residents, physicians and general population were identified by matching with age and sex in 2009 in a 1:2 ratio. The risk for thyroid diseases was compared between the physicians and general population and among physicians by tracing their medical histories between 2006 and 2012. RESULTS: In total, 28,649 physicians and 57,298 general population were identified. Physicians had a higher risk for overall thyroid diseases than the general population [odds ratio (OR): 1.27; 95% confidence interval (CI): 1.10-1.47], including individual thyroid disease: thyroid cancer (OR: 1.89; 95% CI: 1.22-2.95), hypothyroidism (OR: 1.64; 95% CI: 1.23-2.18) and thyroiditis (OR: 1.48; 95% CI: 1.00-2.19). CONCLUSIONS: We showed that physicians had a significantly higher risk for thyroid diseases than the general population. This reminds us to pay more attention to thyroid diseases in physicians. Further studies about the underlying mechanisms are warranted.

Interleukin enhancer-binding factor 3 promotes breast tumor progression by regulating sustained urokinase-type plasminogen activator expression.

Sustained urokinase-type plasminogen activator (uPA) expression is detected in aggressive breast tumors. Although uPA can be transiently upregulated by diverse extracellular stimuli, sustained, but not transiently upregulated uPA expression contributes to breast cancer invasion/metastasis. Unfortunately, how sustained uPA expression is achieved in invasive/metastatic breast cancer cells is unknown. Here, we show that sustained and transiently upregulated uPA expression are regulated by distinct mechanisms. Using a collection of transcription factor-targeted small-interfering RNAs, we discovered that interleukin enhancer-binding factor 3 (ILF3) is required for sustained uPA expression. Two discrete mechanisms mediate ILF3 action. The first is that ILF3 activates uPA transcription by binding to the CTGTT sequence in the nucleotides -1004∼-1000 of the uPA promoter; the second is that ILF3 inhibits the processing of uPA mRNA-targeting primary microRNAs (pri-miRNAs). Knockdown of ILF3 led to significant reduction in in vitro cell growth/migration/invasion and in vivo breast tumor development. Importantly, immunohistochemistry (IHC) showed that nuclear ILF3, but not cytoplasmic ILF3 staining correlates with elevated uPA level and higher grades of human breast tumor specimens. Nuclear localization of ILF3 highlights the role of ILF3 in sustained uPA expression as a transcription activator and pri-miRNA processing blocker. In conclusion, this study shows that ILF3 promotes breast tumorigenicity by regulating sustained uPA expression.

Effect of camostat mesilate on the expression of pancreatitis-associated protein (PAP), p8, and cytokines in rat spontaneous chronic pancreatitis.

An oral protease inhibitor, camostat mesilate (CM) has been used clinically for chronic pancreatitis (CP) in Japan, but it lacks enough scientific evidence of its effectiveness. The aim of this study was to analyze the effect of CM on the gene expressions of pancreatitis-associated protein (PAP), p8, and cytokines such as interleukin-6 and transforming growth factor-beta1 in spontaneous CP model (WBN/Kob rats). CM (10 mg/100 g body weight), mixed in MB-3 diet, was administered orally and gene expressions were analyzed by reverse transcription-polymerase chain reaction. In untreated WBN/Kob rats, the gene expressions of all the four factors peaked at 12 weeks, whereas they were significantly suppressed in the CM-treated rats. CM significantly increased the body weight and pancreatic wet weight, and it significantly inhibited inflammatory changes and fibrosis of the pancreas. These results suggest that CM inhibits pancreatic inflammation and fibrosis through the suppression of gene expressions of PAP, p8, and cytokines in CP.

P8 expression is induced in acinar cells during chronic pancreatitis.

The p8 gene is barely expressed in the normal pancreas, but is overexpressed in acute pancreatitis. To elucidate the dynamic expression of p8 mRNA and its significance in the course of chronic pancreatitis, we investigated the p8 expression in spontaneous chronic pancreatitis in the WBN/Kob rat as well as in humans and arginine-treated rat pancreatic acinar AR4-2J cells. p8 mRNA was significantly increased at 12 weeks when chronic pancreatitis first appeared in the WBN/Kob rats. p8 was immunolocalized in the acinar cell nuclei. Acinar cell apoptosis was significantly increased at 12 and 20 weeks in the WBN/Kob rats. In AR4-2J cells, p8 mRNA was significantly induced at 4 hr after arginine addition. Apoptosis of AR4-2J cells was not increased during the strong expression of p8 mRNA. These results suggest that p8 is induced in the acinar cells during chronic pancreatitis as the self-defence mechanism against proapoptotic insults.

Pertussis toxin inhibits induction of tissue-specific autoimmune disease by disrupting G protein-coupled signals.

Pertussis toxin (PTX) has been used for many years as an adjuvant that promotes development of tissue-specific experimental autoimmune diseases such as experimental autoimmune encephalomyelitis, experimental autoimmune uveitis (EAU), and others. Enhancement of vascular permeability and of Th1 responses have been implicated in this effect. Here we report a surprising observation that, in a primed system, PTX can completely block the development of EAU. Disease was induced in B10.RIII mice by adoptive transfer of uveitogenic T cells, or by immunization with a uveitogenic peptide. A single injection of PTX concurrently with infusion of the uveitogenic T cells, or two injections 7 and 10 days after active immunization, completely blocked development of EAU. EAU also was prevented by a 1-h incubation in vitro of the uveitogenic T cells with PTX before infusing them into recipients. Uveitogenic T cells treated with PTX in vitro and lymphoid cells from mice treated with PTX in vivo failed to migrate to chemokines in a standard chemotaxis assay. Neither the isolated B-oligomer subunit of PTX that lacks ADP ribosyltransferase activity nor the related cholera toxin that ADP-ribosylates G(s) (but not G(i)) proteins blocked EAU induction or migration to chemokines. We conclude that PTX present at the time of cell migration to the target organ prevents EAU, and propose that it does so at least in part by disrupting signaling through G(i) protein-coupled receptors. Thus, the net effect of PTX on autoimmune disease would represent an integration of enhancing and inhibitory effects.

Expression of tumor necrosis factor-alpha, interleukin-6, and interferon-gamma in spontaneous chronic pancreatitis in the WBN/Kob rat.

To clarify the pathophysiological significance of cytokines in chronic pancreatitis (CP), we analyzed tissue expressions of various cytokines in the onset and progression of spontaneous CP in the WBN/Kob rat. Four-week-old male WBN/Kob rats were fed a special pellet diet (MB-3) for 20 weeks, and 6 rats were killed every 4 weeks. Pathologically, CP occurred at 12 weeks and progressed thereafter. The inflammation and fibrosis peaked at 12 and 16 weeks, respectively. By semiquantitative reverse transcription-polymerase chain reaction, the expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and interferon (IFN)-gamma mRNAs peaked at 8, 12, and 16 weeks, respectively. Immunohistochemistry showed IL-6 expression in infiltrating inflammatory cells and vascular endothelial cells, whereas TNF-alpha was expressed in both acinar and infiltrating cells. IFN-gamma was localized to acinar, infiltrating and ductal cells, and its expression intensity showed significant correlation with those of fibrosis, type III collagen and alpha-smooth muscle actin. The in situ hybridization results were consistent with the RT-PCR data. These results suggest that tissue expressions of TNF-alpha and IL-6 are involved in the onset of pancreatitis and that IFN-gamma expression is related to the progression of CP.

Overexpression of p8 is inversely correlated with apoptosis in pancreatic cancer.

A recently identified gene, p8, has cell growth-promoting activity and is strongly induced in acute pancreatitis. In this study, we detected p8 and single-stranded DNA (ssDNA) for apoptosis by immunohistochemistry in human pancreatic cancer. The p8 was overexpressed (>30% per 1000 cancer cells) in 26 of 44 (59%) pancreatic cancers, and apoptosis (ssDNA-positive cells >10% per 1000 cancer cells) was recognized in 18 of 44 (41%) pancreatic cancers. There was a significant inverse correlation between the p8 overexpression and apoptosis (P < 0.05). Moreover, the expression pattern of high p8 and low ssDNA was seen significantly more often in lower age (<65 years), in moderately or poorly differentiated cancers, and in node-positive cases (P < 0.05). The p8 expression and apoptosis were not significantly correlated with survival. These results suggest that p8 overexpression is involved in antiapoptotic activity and the biological characteristics of pancreatic cancer.

Expression of clusterin in pancreatic acinar cell injuries in vivo and in vitro.

Clusterin is a secretory glycoprotein that is highly induced in several tissues in response to injury. The pathophysiologic significance of clusterin in the pancreas remains largely unknown. The aim of this work was to examine whether clusterin is expressed in spontaneous chronic pancreatitis in the WBN/Kob rat and to investigate the relationship between clusterin and apoptosis in pancreatic acinar AR4-2J cells. In the in vivo study, 4-week-old male WBN/Kob rats developed chronic pancreatitis at 12 weeks. Clusterin mRNA was expressed after 12 weeks and then decreased. Immunohistochemistry showed clusterin expression in the acinar cells. In the in vitro study, clusterin mRNA and protein were strongly induced in AR4-2J cells treated either with arginine, menadione, tumor necrosis factor-alpha or transforming growth factor-beta1. In the time course study with arginine or menadione, clusterin mRNA was expressed after 4 hours and peaked at 8 and 24 hours, whereas DNA fragmentation peaked at 72 hours. Our results show that clusterin is overexpressed in the pancreas at the onset of chronic pancreatitis in vivo and in cultured acinar cells in response to various stimuli in vitro, suggesting that clusterin is a defense mechanism of the exocrine pancreas.