Role of Interleukin-36 in inflammatory joint diseases. / ç™½ä»‹ç´ -36åœ¨å ³èŠ‚ç‚Žæ€§ç–¾ç— ä¸­çš„ä½œç”¨.

Interleukin (IL)-36 is a family of cytokines that belongs to the larger IL-1 superfamily. IL-36 agonist/antagonist binds to the interleukin-36 receptor involving in physiological inflammation regulation and pathogenesis of many inflammatory diseases. In inflammatory joint diseases, the expression of IL-36 changes, and some studies have initially explored the role of IL-36 in these diseases. In psoriatic arthritis, IL-36 signal mediates plasma cell and fibroblast-like synoviocyte crosstalk presenting IL-36 agonist/antagonist imbalance. In rheumatoid arthritis, IL-36 agonists induce fibroblast-like synoviocyte to produce pro-inflammatory factors, while IL-36 antagonist deficiency leads to lesion progression. In osteoarthritis, IL-36 agonists induce chondrocytes to produce catabolic enzymes and pro-inflammatory factors. This article reviews the expression and function of IL-36 in different inflammatory joint diseases to provide a reference for revealing their pathogenic mechanisms and discovering therapeutic targets.

The functions and roles of sestrins in regulating human diseases.

Sestrins (Sesns), highly conserved stress-inducible metabolic proteins, are known to protect organisms against various noxious stimuli including DNA damage, oxidative stress, starvation, endoplasmic reticulum (ER) stress, and hypoxia. Sesns regulate metabolism mainly through activation of the key energy sensor AMP-dependent protein kinase (AMPK) and inhibition of mammalian target of rapamycin complex 1 (mTORC1). Sesns also play pivotal roles in autophagy activation and apoptosis inhibition in normal cells, while conversely promoting apoptosis in cancer cells. The functions of Sesns in diseases such as metabolic disorders, neurodegenerative diseases, cardiovascular diseases, and cancer have been broadly investigated in the past decades. However, there is a limited number of reviews that have summarized the functions of Sesns in the pathophysiological processes of human diseases, especially musculoskeletal system diseases. One aim of this review is to discuss the biological functions of Sesns in the pathophysiological process and phenotype of diseases. More significantly, we include some new evidence about the musculoskeletal system. Another purpose is to explore whether Sesns could be potential biomarkers or targets in the future diagnostic and therapeutic process.

Enhanced osteogenesis of quasi-three-dimensional hierarchical topography.

Natural extracellular matrices (ECMs) are three-dimensional (3D) and multi-scale hierarchical structure. However, coatings used as ECM-mimicking structures for osteogenesis are typically two-dimensional or single-scaled. Here, we design a distinct quasi-three-dimensional hierarchical topography integrated of density-controlled titania nanodots and nanorods. We find cellular pseudopods preferred to anchor deeply across the distinct 3D topography, dependently of the relative density of nanorods, which promote the osteogenic differentiation of osteoblast but not the viability of fibroblast. The in vivo experimental results further indicate that the new bone formation, the relative bone-implant contact as well as the push-put strength, are significantly enhanced on the 3D hierarchical topography. We also show that the exposures of HFN7.1 and mAb1937 critical functional motifs of fibronectin for cellular anchorage are up-regulated on the 3D hierarchical topography, which might synergistically promote the osteogenesis. Our findings suggest the multi-dimensions and multi-scales as vital characteristic of cell-ECM interactions and as an important design parameter for bone implant coatings.

[Progress in study on the role of metabolomics in toxic effects of environmental pollutants and the underlying mechanism].

Metabolomics methods were applied in the study of the toxicity of environmental pollutants. It has been shown that exposure to heavy metals such as mercury, arsenic, cadmium, chromium and lead could cause significant changes in energy, lipids, nucleic acids and amino acids in mammalian cells. After exposure to benzo(a)pyrene [B(a)P], the glands of Pinctada pumila could produce various changes, such as energy metabolic disorder, cell damage, signal transduction disorder, oxidative stress and osmotic disorder. Persistent organic compounds polychlorinated biphenyls (PCBs) could exert toxic effects on Zebrafish embryos through affecting amino acid metabolism, DNA and protein methylation and biosynthesis. After exposure to endocrine disruptors, such as nonylphenol, octylenediester phthalate and bisphenol propane, goldfish showed energy, lipid and nucleic acid metabolic disorders.

[Relationship between the gene polymorphisms of oxidative metabolism enzyme of exogenous chemicals and the susceptibility to neoplasms].

The gene polymorphisms of human being will cause abnormality in the expression of corresponding gene, which is closely related to the physiological function and disease. Cytochrome P450, cyclooxygenase and lipoxygenase are vital enzymes that mediated the oxidative metabolism process for exogenous chemicals, and play important roles in activating the indirect carcinogens and metabolizing clinical drug; the gene polymorphisms of these enzymes can change the expression and activity of enzymes, affect the metabolic transformation of carcinogens, and then give rise to difference in the susceptibility to neoplasms. Studying the relationship between the gene polymorphisms of oxidative metabolism enzyme for endogenous and exogenous chemicals and the susceptibility to neoplasms can provide scientific basis for probing into the genetic markers and the pathogenesis of neoplasms.

[Expression of 5-lipoxygenase in human tissues and its association with disease].

5-Lipoxygenase, one of lipoxygenase isozymes, is a well-studied oxidative metabolism enzyme. It widely exists in various human tissues and cells, participates in the oxidative metabolism of endogenous and exogenous chemicals, and produces a variety of metabolites, all of which contribute to the occurrence of human diseases, such as inflammation, asthma, atherosclerosis, and tumor and so on. The expression of 5-lipoxygenase is at low level in normal human tissues while at high level in abnormal tissues. 5-Lipoxygenase is closely related to many kinds of diseases in human ovary, brain, cardiovascular system, lung, liver, pancreas and other tissues. The abnormal expression of 5-lipoxygenase tends to promote the development of the disease.

DNA-PKcs associates with PLK1 and is involved in proper chromosome segregation and cytokinesis.

Accurate mitotic regulation is as important as intrinsic DNA repair for maintaining genomic stability. It is believed that these two cellular mechanisms are interconnected with DNA damage. DNA-PKcs is a critical component of the non-homologous end-joining pathway of DNA double-stranded break repair, and it was recently discovered to be involved in mitotic processing. However, the underlying mechanism of DNA-PKcs action in mitotic control is unknown. Here, we demonstrated that depletion of DNA-PKcs led to the dysregulation of mitotic progression in response to DNA damage, which eventually resulted in multiple failures, including failure to segregate sister chromatids and failure to complete cytokinesis, with daughter cells becoming fused again. The depletion of DNA-PKcs resulted in a notable failure of cytokinesis, with a high incidence of multinucleated cells. There were also cytoplasmic bridges containing DNA that continuously connected the daughter cells after DNA damage was induced. Phosphorylated DNA-PKcs (T2609) colocalizes with PLK1 throughout mitosis, including at the centrosomes from prophase to anaphase and at the kinetochores from prometaphase to metaphase, with accumulation at the midbody during cytokinesis. Importantly, DNA-PKcs was found to associate with PLK1 in the mitotic phase, and the depletion of DNA-PKcs resulted in the overexpression of PLK1 due to increased protein stability. However, deficiency in DNA-PKcs attenuated the recruitment of phosphorylated PLK1 to the midbody but not to the kinetochores and centrosomes. Our results demonstrate the functional association of DNA-PKcs with PLK1, especially in chromosomal segregation and cytokinesis control.

[Study on activation of benzo(a)pyrene and DNA damage mediated by lipoxygenase in human bronchial epithelial cells].

OBJECTIVE: The oxidation of benzo (a) pyrene mediated by 5-lipoxygenase (5-LOX) were investigated in HBE cells in order to provide further proof that lipoxygenase is the alternative pathway for the oxidation of xenobiotics. METHODS: Enzymic experiment: Soybean lipoxygenase (SLO), substrate (benzo[a] pyrene) and other component react in the enzymic system and the reaction product are detected by spectrophotometry. At the same time, in vitro detect of benzo (a) pyrene-DNA adducts with a UV spectrophotometer and HPLC. Cellular experiment: After HBE cells exposure to different poison (B[a]P 4, 8, 16, 32, 64, 128µmol/L, AA-861, naproxen or α- naphthoflavone 0.1, 1, 10 µmol/L) for 24 hours, the effect of benzo (a) -pyrene on cell survival rate were assessed by reductions of tetrazolium dye (MTT) and flow cytometry in cultured HBE cells, and the protein expressions of 5-lipoxygenase in the cells are tested by western-blot, and the DNA damages by the single cell gel electrophoresis. And then, the effect of the specific inhibitor of 5-lipoxygenase (AA-861) on 5-lipoxygenase protein expression and DNA damage in the cells are detected. RESULTS: SLO can catalyze the co-oxidation of benzo (a) pyrene to generate benzo (a) pyrene-7,8-epoxide in the presence of hydrogen peroxide. GTP can inhibit the reaction , the IC50 value is 0.46 mg/L, the model equation is Probit (P) = 0.8985+2.6824 Log (dose). SLO can catalyze the co-oxidation of benzo (a) pyrene to generate a new product, but fail to form DNA adducts in vitro. HBE cell viability decreased with the benzo (a) pyrene concentration increased , but AA-861 and naproxen can inhibit it. Flow cytometry and single cell gel electrophoresis experiments show, Benzo (a) pyrene can induce 5-lipoxygenase protein expression, but AA-861 cannot in HBE. Benzo (a) pyrene causes toxic action and DNA damage in HBE, which can significantly inhibit by AA-861, the difference is statistically significant (P < 0.05). CONCLUSIONS: The co-oxidate of benzo (a) pyrene by 5-LOX turns into electrophiles that covalently bind to DNA and induce DNA damage, which can be significantly inhibited by AA-861.

In vivo comparison of bone formation on titanium implant surfaces coated with biomimetically deposited calcium phosphate or electrochemically deposited hydroxyapatite.

PURPOSE: The purpose of this study was to investigate and compare bone formation on titanium implant surfaces coated with biomimetically deposited calcium phosphate (BDCaP) or electrochemically deposited hydroxyapatite (EDHA). MATERIALS AND METHODS: The implants were separated into three groups: a control group, a BDCaP group, and an EDHA group. Surface analysis was performed by field-emission scanning electron microscopy, x-ray diffractometry, and Fourier transform infrared spectroscopy. Implants were inserted in a randomized arrangement into rabbit tibiae. After 2, 4, and 8 weeks, the tibiae were retrieved and prepared for histomorphometric evaluation. RESULTS: Field-emission scanning electron microscopy showed that the BDCaP crystals were flakelike and the EDHA crystals were rodlike with a hexagonal cross section. X-ray diffractometric patterns and Fourier transform infrared spectroscopy spectra showed that the BDCaP coating consisted of HA and octacalcium phosphate, whereas the EDHA coating consisted of HA. Histologic observation showed that new bone on the EDHA-coated implant became mature after 4 weeks, while new bone on the control and BDCaP-coated implants was mature after 8 weeks. The EDHA implant showed significantly greater BIC and bone area compared to the control and BDCaP implants during 4 to 8 weeks. The BDCaP coating failed to show increased bone formation during the test period. CONCLUSION: The present EDHA coating has good bone formation properties, while the BDCaP coating has weaker bone formation properties.

Biomechanical comparison of biomimetically and electrochemically deposited hydroxyapatite-coated porous titanium implants.

PURPOSE: The purpose of this study was to investigate the effects of biomimetically and electrochemically deposited hydroxyapatite on the fixation of an implant with bone tissue. MATERIALS AND METHODS: Implants were separated into 3 groups: roughened group, biomimetically deposited calcium-phosphorus (BDCaP) group, and electrochemically deposited hydroxyapatite (EDHA) group. We randomly inserted 90 implants into the femurs of 45 rabbits. After 2, 4, and 8 weeks, the femurs were retrieved and prepared for removal torque tests (RTQs) and field-emission scanning electron microscopy observation. RESULTS: During the test period, the EDHA group showed significantly greater RTQ values than did the roughened group and BDCaP group. The BDCaP group failed to increase the RTQ values compared with the roughened group. Field-emission scanning electron microscopy observation showed that the amount of attached bone tissue on the EDHA-coated implant surface was more than that on the roughened and BDCaP-coated implant surfaces during the test period. CONCLUSION: The electrochemical hydroxyapatite coating contributes to the fixation between bone and implant compared with the roughened surface, whereas the biomimetic calcium-phosphorus coating has little effect on the fixation.

[Cross-talk between Notch1 and epidermal growth factor receptor signalling in regulating cell proliferation of human tongue squamous carcinoma cells].

OBJECTIVE: To investigate the cross-talk between Notch1 and epidermal growth factor receptor (EGFR) signaling in regulating the cellular proliferation of human tongue squamous cell carcinoma (SCC). METHODS: Human tongue SCC cell line Tca8113 cells was transiently transfected with the vector encoding exogenous intracellular fragment of Notch1 and the vector encoding the specific short hairpin RNA (shRNA) targeting EGFR respectively and were treated by AG1478, an inhibitor of receptor tyrosine kinases, for elucidating the effects of constitutive activation, EGFR gene silencing and blocking EGFR signaling upon cellular proliferation and expression of Notch1 and EGFR. The mRNA and protein levels of Notch1 and EGFR were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot, respectively. The cellular proliferation was evaluated by methyl thiazolyl tetrazolium (MTT) assay. RESULTS: Constitutive activation of Notch1 resulted in inhibition of cellular proliferation, and up-regulation of Notch1 (1.102 +/- 0.135, 0.243 +/- 0.032, P < 0.05) but down-regulation of EGFR (0.083 +/- 0.009, 0.605 +/- 0.075, P < 0.05) at the the mRNA and protein levels. Silencing of EGFR gene resulted in inhibition of cell proliferation, and down-regulation of EGFR (0.148 +/- 0.019, 1.175 +/- 0.132, P < 0.05) but up-regulation of Notch1 (0.978 +/- 0.115, 0.083 +/- 0.009, P < 0.05) at the mRNA and protein levels. Blocking EGFR signaling had no significant effect upon EGFR expression (P > 0.05), but resulted in inhibition of cellular proliferation and up-regulation of Notch1 (P < 0.05) at the mRNA and protein levels. CONCLUSION: There might be a cross-talk of bi-directional control between Notch1 and EGFR signaling in regulating the cellular proliferation of human tongue SCC cells.

[Protein expression of 5-lipoxygenase and activation and cytotoxicity of Benzidine in human bronchial epithelial cells].

OBJECTIVE: To investigate the effect of intracellular 5-lipoxygenase on oxidation of benzidine in HBE cells and to provide further evidence that lipoxygenase is an alternative pathway for the oxidation of xenobiotics mediated by cytochrome P450. METHODS: Enzyme system test: Soybean lipoxygenase (SLO), substrate (benzidine) and other components reacted in the enzyme system, followed by detection of the reaction products by spectrophotometry. In vitro test: After HBE cells were exposed to benzidine, the protein levels of 5-lipoxygenase in HBE cells were assessed by Western-blot, and the DNA damage by the single cell gel electrophoresis. At last, the effect of the specific inhibitor of 5-lipoxygenase (AA861) on 5-lipoxygenase protein expression and DNA damage in HBE cells were detected. RESULTS: SLO could catalyze the co-oxidation of benzidine to generate benzidine diimine in the presence of hydrogen peroxide. Under optimal condition, numax value of the oxidation of benzidine catalyzed by SLO was 1.42 nmol*min(-1) SLO, and the Km value of benzidine was 1.48 mmol/L. EGCG could inhibit the oxidation of benzidine by SLO. Benzidine could induce 5-lipoxygenase protein expression in HBE cells, but AA861 was invalid. Benzidine caused DNA damage in HBE cells, which could be significantly inhibited by AA861. CONCLUSION: 5-LOX protein expression in HBE cells can be regulated by benzidine, which suggests that the co-oxidation of benzidine by 5-LOX could produce into electrophile that could covalently bind to DNA and induce DNA damage, which could be one of the mechanisms for carcinogenesis of BZD. 5-LOX inhibitor AA861 can inhibit this effect.

[Advances in the research of lipoxygenase inhibitors].

Lipoxygenase is a protein with non-heme iron atom, which has been discovered in many animals and plants. Lipoxygenase which has a close relationship with human tumors, inflammatory diseases, asthma, arteriosclerosis, and toxic action of chemicals could not only di-oxygenate endogenous polyunsaturated fatty acid to yield bioactive factors such as leukotrienes(LTs), but also has co-oxidation activity to activate xenobiotics. Lipoxygenase inhibitors include hydroxamic acid derivatives, nordihydroguaiaretic acid, flavonoids, FLAP inhibitors and so on. All of them can effectively restrain the catalytic action of lipoxygenase. Literatures demonstrate that the inhibitors can block the formation of relevant bioactive factors and toxic products of xenobiotics clinically which are used to prevent and cure the relevant diseases to keep people healthy.

Poly (ADP-ribose) glycohydrolase silencing-mediated maintenance of H2A and downregulation of H2AK9me protect human bronchial epithelial cells from benzo(a)pyrene-induced carcinogenesis.

Poly (ADP-ribosylation) is a key post-translational modification (PTM), and poly (ADP-ribose) glycohydrolase (PARG) is the main enzyme that hydrolyzes poly (ADP-ribose) in eukaryotic organisms. Our previous findings suggested that knockdown of PARG attenuates benzo(a)pyrene (BaP) carcinogenesis. However, the mechanisms underlying PARG-mediated protective effects remain limited. In this study, the expression levels of histones were analyzed by Western blotting and immunofluorescence. Histone H2A levels were abnormally decreased by BaP-induced carcinogenesis, but were maintained by knockdown of PARG in the 16HBE human bronchial epithelial cell line. The interaction between poly (ADP-ribose) and H2A was confirmed by co-immunoprecipitation. PARG-related modifications in H2A were profiled by immune antibody enrichment coupled with mass spectrometry. H2AK5ac, H2AK9ac, H2AK13ac, H2A.ZK4K7K11ac, and H2AK9me were expressed in BaP-transformed 16HBE (BTC-16HBE) cells, but were not detectable in normal 16HBE or BaP-transformed 16HBE cells with knockdown of PARG (BTC-shPARG). Further verification by Western blotting indicated that H2AK9me was elevated in BTC-16HBE cells but decreased in BTC-shPARG cells. These findings suggest that knockdown of PARG protects against BaP-induced carcinogenesis in 16HBE cells by downregulating H2AK9me. Our in vivo studies confirmed that PARG silencing decreased H2AK9me levels, thereby countering the carcinogenic teratogenic effects induced by BaP.

[Expression of pJAK, pERK and Cyclin D1 proteins in squamous-cell carcinoma of tongue].

OBJECTIVE: To investigate the expression of JAK, ERK and Cyclin D proteins in squamous-cell carcinoma of tongue. METHODS: The expression of JAK, ERK and Cyclin D1 proteins was determined with SP immunohistochemical method in 30 cases of lingual Squamous cell carcinoma, 20 of normal lingual mucosa, 10 of mild epithelial dysplasia and 20 of severe epithelial dysplasia. RESULTS: The expression of pJAK in lingual squamous-cell carcinoma and epithelial dysplasia was stronger than that of normal lingual mucosa (chi2=37.54, P<0.01), and the expression of pJAK in lingual squamous-cell carcinoma was significantly higher than that of the epithelial dysplasia (chi2=6.83, P<0.05). pJAK expression in squamous-cell carcinoma of low-middle differentiation was stronger than that of high differentiation. There was no significant difference in pERK expression among lingual squamous-cell carcinoma, normal lingual mucosa and epithelial dysplasia. There was a significantly positive correlation between pJAK and Cyclin D1 expression in SCC (r=0.619, P<0.05). There was no significant correlation between the expression of pERK and Cyclin D1 (r=0.231, P>0.05). CONCLUSION: Over-expression of pJAK and Cyclin D1 may be associated with the occurrence and development of squamous-cell carcinoma of the tongue.

15,16-dihydrotanshinone I Induces Apoptosis and Inhibits the Proliferation, Migration of Human Osteosarcoma Cell Line 143B in vitro.

BACKGROUND: 15,16-dihydrotanshinone I (DHTI), a lipophilic tanshinone extracted from Danshen root (Salvia miltiorrhiza Bunge), has been reported to function as an antitumor agent. However, its activity on osteosarcoma (OS), the most common primary malignant bone tumor, is unclear. OBJECTIVE: This study aimed to determine the effects of DHTI treatment on proliferation, apoptosis and migration of human OS cell line 143B and investigate the possible underlying molecular mechanisms. METHOD: Human cell line 143B was used as a model for investigation of the inhibitory effects of DHTI on osteosarcoma. Cell proliferation was evaluated by MTT assays, while cell cycle progression, apoptosis and cell migration were analyzed by flow cytometer, caspase activity assays and scratch migration assays. qRT-PCR and western blot were carried out to detect the expression levels of representative genes and proteins during physiological processes examined above. RESULTS: DHTI treatment inhibited the proliferation of 143B cells in a dose- and time-dependent manner through arresting cells in G1 phase by reducing the expression of cyclin D1, cyclin E1, CDK2, CDK4, CDK6, p-Rb, E2F1, SKP2 and increasing the expression of P53, P21cip1, P27kip1. In addition, DHTI induced apoptosis of 143B cells through caspase pathways to activate caspase-3, caspase-8, caspase-9, Bax, and PARP cleavage but reduce the expression of Bcl-2. Furthermore, DHTI treatment attenuated cell migration by down-regulating adhesion molecules VCAM-1 and ICAM-1. CONCLUSION: These findings suggest that DHTI could be a novel and efficient therapeutic candidate for OS treatment and further detailed investigation is warranted.

Increased levels of CK19 mRNA in oral squamous cell carcinoma tissue detected by relative quantification with real-time polymerase chain reaction.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in the oral and maxillofacial region and has a poor prognosis. Cytokeratin 19 (CK19) is a component of cytoskeleton protein. Previous studies have reported abnormal expression of CK19 protein in OSCC tissue. This study is to investigate the quantitative level of CK19 gene transcript in OSCC tissue as well as its clinical significance. Thirty-one OSCC patients (26 males and 5 females) took part in the present study, aged 34-78 years (mean 58.2 years). The level of CK19 mRNA was detected using fluorescent quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) in cancerous and paracancerous tissues. The relative quantification in cancerous tissue compared with paracancerous tissue was calculated using the 2(-DeltaDeltaCt) equation. The level of CK19 mRNA in cancerous tissue from OSCC patients was 2.21-fold higher than that in paracancerous tissue (P=0.020), and the amplicon was specific without genomic DNA contamination. The level of CK19 mRNA correlated significantly with the pathological differentiation grade of OSCC tissue (P=0.025), with poorer differentiation indicating a higher level of CK19 mRNA. These results suggest that fluorescent quantitative real-time RT-PCR is accurate and reliable for the detection of CK19 gene transcript levels in OSCC tissue. The level of CK19 mRNA was increased in OSCC tissue, and this was significantly correlated with the pathological differentiation grade.

An animal model for inducing anterior disc displacement of the temporomandibular joint.

AIMS: To develop an animal model of anterior disc displacement (ADD) without the need for opening the temporomandibular joint (TMI) capsule. METHODS: Thirty-two healthy adult Japanese white rabbits were used in this study. Four rabbits were dissected to familiarize the investigators with the anatomy of the TMJ. Sixteen animals were subjected to surgical ADD in the right TMJ, 8 animals had a sham operation, and 4 animals were not operated (normal controls). Four rabbits from the experimental ADD group and 2 from the sham group were sacrificed 1, 2, 4, and 8 weeks, respectively. The rabbits in normal control group were sacrificed at the beginning of the experiment. Animal behaviors as well as macro- and microchanges in the TMJs were investigated. RESULTS: Fifteen right TMJ discs in the 16 experimental rabbits were successfully displaced anteriorly, and the degree of ADD in the experimental group was similar. The mandible of each ADD rabbit deviated to the left side with inclined attrition of the incisors. Some histologic changes appeared in the experimental TMJs. CONCLUSION: This ADD technique without the need for opening the TMJ capsule is effective, and the model is suitable for studying ADD of the TMJ.

Dose-Response Relationship between Cumulative Occupational Lead Exposure and the Associated Health Damages: A 20-Year Cohort Study of a Smelter in China.

Long-term airborne lead exposure, even below official occupational limits, has been found to cause lead poisoning at higher frequencies than expected, which suggests that China's existing occupational exposure limits should be reexamined. A retrospective cohort study was conducted on 1832 smelting workers from 1988 to 2008 in China. These were individuals who entered the plant and came into continuous contact with lead at work for longer than 3 months. The dose-response relationship between occupational cumulative lead exposure and lead poisoning, abnormal blood lead, urinary lead and erythrocyte zinc protoporphyrin (ZPP) were analyzed and the benchmark dose lower bound confidence limits (BMDLs) were calculated. Statistically significant positive correlations were found between cumulative lead dust and lead fumes exposures and workplace seniority, blood lead, urinary lead and ZPP values. A dose-response relationship was observed between cumulative lead dust or lead fumes exposure and lead poisoning (p < 0.01). The BMDLs of the cumulative occupational lead dust and fumes doses were 0.68 mg-year/m³ and 0.30 mg-year/m³ for lead poisoning, respectively. The BMDLs of workplace airborne lead concentrations associated with lead poisoning were 0.02 mg/m³ and 0.01 mg/m³ for occupational exposure lead dust and lead fume, respectively. In conclusion, BMDLs for airborne lead were lower than occupational exposure limits, suggesting that the occupational lead exposure limits need re-examination and adjustment. Occupational cumulative exposure limits (OCELs) should be established to better prevent occupational lead poisoning.