Correlation between expression of Lin28B and C-myc in patients with laryngeal squamous cell carcinoma and clinicopathological features and prognosis. / Lin28B和C-mycè›‹ç™½åœ¨å–‰é³žç™Œä¸­çš„è¡¨è¾¾åŠå ¶ä¸Žä¸´åºŠç— ç†ç‰¹å¾å’Œé¢„åŽçš„ç›¸å ³æ€§.

OBJECTIVES: Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of head and neck. Screening of target genes for malignant tumor therapy is one of the focuses of cancer research, with proto-oncogene and tumor suppressor gene as the breakthrough. It has become an urgent need to find the target gene related to the treatment and prognosis of LSCC.This study aims to explore the role of Lin28B and C-myc in LSCC by detecting the expressions of these two proteins and analyze the correlation between the expression of Lin28B and C-myc and clinicopathological features and prognosis of LSCC. METHODS: We detected the expression of Lin28B and C-myc proteins in 102 specimens of LSCC and 90 specimens of adjacent tissues by immunochemistry, and analyzed the correlation between Lin28B and C-myc protein expressions in LSCC as well as the correlation between the expressions of the two proteins and the clinicopathological features of LSCC. At the same time, the Kaplan-Meier method was used to analyze the relation between Lin28B and C-myc protein levels with the postoperative survival rate of LSCC patients. RESULTS: The protein levels of Lin28B and C-myc in the LSCC tissnes were significantly higher than those in the adjacent tissues (both P<0.05),and there was a positive correlation between the expression of Lin28B and C-myc in LSCC (r＝0.476, P<0.05). The expression of Lin28B protein was closely related to age, lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). while the expression of C-myc protein was closely related to lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). A relevant survival analysis showed that in patients with higher level of Lin28B (P＝0.001) or C-myc protein (P<0.001), the postoperative survival rate was relatively low. CONCLUSIONS: Lin28B and C-myc proteins are highly expressed in LSCC with a positive correlation. Furthermore, they are closely related to lymph node metastasis, clinical stage, tumor size, pathological differentiation and prognosis, suggesting that both Lin28B and C-myc might be involved in the occurrence and development of LSCC.

Deletion of Neuronal CuZnSOD Accelerates Age-Associated Muscle Mitochondria and Calcium Handling Dysfunction That Is Independent of Denervation and Precedes Sarcopenia.

Skeletal muscle suffers atrophy and weakness with aging. Denervation, oxidative stress, and mitochondrial dysfunction are all proposed as contributors to age-associated muscle loss, but connections between these factors have not been established. We examined contractility, mitochondrial function, and intracellular calcium transients (ICTs) in muscles of mice throughout the life span to define their sequential relationships. We performed these same measures and analyzed neuromuscular junction (NMJ) morphology in mice with postnatal deletion of neuronal Sod1 (i-mn-Sod1-/- mice), previously shown to display accelerated age-associated muscle loss and exacerbation of denervation in old age, to test relationships between neuronal redox homeostasis, NMJ degeneration and mitochondrial function. In control mice, the amount and rate of the decrease in mitochondrial NADH during contraction was greater in middle than young age although force was not reduced, suggesting decreased efficiency of NADH utilization prior to the onset of weakness. Declines in both the peak of the ICT and force were observed in old age. Muscles of i-mn-Sod1-/- mice showed degeneration of mitochondrial and calcium handling functions in middle-age and a decline in force generation to a level not different from the old control mice, with maintenance of NMJ morphology. Together, the findings support the conclusion that muscle mitochondrial function decreases during aging and in response to altered neuronal redox status prior to NMJ deterioration or loss of mass and force suggesting mitochondrial defects contribute to sarcopenia independent of denervation.

Anti-Diabetic Effect of a Shihunine-Rich Extract of Dendrobium loddigesii on 3T3-L1 Cells and db/db Mice by Up-Regulating AMPK-GLUT4-PPARα.

The stems of Dendrobium loddigesii, a Chinese herb, are often used to treat diabetes and its polar extract is rich in shihunine, a water-soluble Orchidaceae alkaloid, but little is known about the anti-diabetes effects and mechanism of shihunine. This study investigated the anti-diabetic effect of a shihunine-rich extract of D. loddigesii (DLS) based on 3T3-L1 cells and db/db mice. The underlying mechanisms were primarily explored using Western blot analysis and immunohistochemical staining. The 3T3-L1 cell experiments showed that DLS can reduce the intracellular accumulation of oil droplets as well as triglycerides (p < 0.001) and promote the 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2deoxyglucose (2-NBDG) uptake of 3T3-L1 cells (p < 0.001). The animal experiments confirmed that after 8 weeks of DLS treatment, the body weight, fasting blood sugar, and serum lipid levels of mice were significantly lowered, and the oral glucose tolerance test and serum insulin level were significantly improved compared to the no-treatment diabetes mellitus group. Further histomorphology observation led to the conclusion that the quantities of islet cells were significantly increased and the increase in adipose cell size was significantly suppressed. The immunohistochemical test of pancreatic tissue revealed that DLS inhibited the expression of cleaved cysteine aspartic acid-specific protease 3 (cleaved caspase-3). Western blot experiments showed that DLS had agonistic effects on adenosine monophosphate (AMP)-activated protein kinase phosphorylation (p-AMPK) and increased the expression levels of peroxisome proliferator-activated receptor α (PPARα) and glucose transporter 4 (GLUT4) in liver or adipose tissues. These data suggest that the shihunine-rich extract of D. loddigesii is an anti-diabetic fraction of D. loddigesii. Under our experimental condition, DLS at a dose of 50 mg/kg has good anti-diabetic efficacy.

Phomopsichin A-D; Four New Chromone Derivatives from Mangrove Endophytic Fungus Phomopsis sp. 33.

Four new chromone derivatives, phomopsichins A-D (1-4), along with a known compound, phomoxanthone A (5), were isolated from the fermentation products of mangrove endophytic fungus Phomopsis sp. 33#. Their structures were elucidated based on comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction or theoretical calculations of electronic circular dichroism (ECD). They feature a tricyclic framework, in which a dihydropyran ring is fused with the chromone ring. Compounds 1-5 showed weak inhibitory activities on acetylcholinesterase as well as α-glucosidase, weak radical scavenging effects on 1,1-diphenyl-2-picrylhydrazyl (DPPH) as well as OH, and weak antimicrobial activities. Compounds 1-4 showed no cytotoxic activity against MDA-MB-435 breast cancer cells. Their other bioactivities are worthy of further study, considering their unique molecular structures.

Six New Polyketide Decalin Compounds from Mangrove Endophytic Fungus Penicillium aurantiogriseum 328.

Six new compounds with polyketide decalin ring, peaurantiogriseols A-F (1-6), along with two known compounds, aspermytin A (7), 1-propanone,3-hydroxy-1- (1,2,4a,5,6,7,8,8a-octahydro-2,5-dihydroxy-1,2,6-trimethyl-1-naphthalenyl) (8), were isolated from the fermentation products of mangrove endophytic fungus Penicillium aurantiogriseum 328#. Their structures were elucidated based on their structure analysis. The absolute configurations of compounds 1 and 2 were determined by ¹H NMR analysis of their Mosher esters; the absolute configurations of 3-6 were determined by using theoretical calculations of electronic circular dichroism (ECD). Compounds 1-8 showed low inhibitory activity against human aldose reductase, no activity of inducing neurite outgrowth, nor antimicrobial activity.

Three-Dimensional Voxel-Wise Quantitative Assessment of Imaging Features in Hepatocellular Carcinoma.

Voxel-wise quantitative assessment of typical characteristics in three-dimensional (3D) multiphase computed tomography (CT) imaging, especially arterial phase hyperenhancement (APHE) and subsequent washout (WO), is crucial for the diagnosis and therapy of hepatocellular carcinoma (HCC). However, this process is still missing in practice. Radiologists often visually estimate these features, which limit the diagnostic accuracy due to subjective interpretation and qualitative assessment. Quantitative assessment is one of the solutions to this problem. However, performing voxel-wise assessment in 3D is difficult due to the misalignments between images caused by respiratory and other physiological motions. In this paper, based on the Liver Imaging Reporting and Data System (v2018), we propose a registration-based quantitative model for the 3D voxel-wise assessment of image characteristics through multiple CT imaging phases. Specifically, we selected three phases from sequential CT imaging phases, i.e., pre-contrast phase (Pre), arterial phase (AP), delayed phase (DP), and then registered Pre and DP images to the AP image to extract and assess the major imaging characteristics. An iterative reweighted local cross-correlation was applied in the proposed registration model to construct the fidelity term for comparison of intensity features across different imaging phases, which is challenging due to their distinct intensity appearance. Experiments on clinical dataset showed that the means of dice similarity coefficient of liver were 98.6% and 98.1%, those of surface distance were 0.38 and 0.54 mm, and those of Hausdorff distance were 4.34 and 6.16 mm, indicating that quantitative estimation can be accomplished with high accuracy. For the classification of APHE, the result obtained by our method was consistent with those acquired by experts. For the WO, the effectiveness of the model was verified in terms of WO volume ratio.

Microglial-Targeted nSMase2 Inhibitor Fails to Reduce Tau Propagation in PS19 Mice.

The progression of Alzheimer's disease (AD) correlates with the propagation of hyperphosphorylated tau (pTau) from the entorhinal cortex to the hippocampus and neocortex. Neutral sphingomyelinase2 (nSMase2) is critical in the biosynthesis of extracellular vesicles (EVs), which play a role in pTau propagation. We recently conjugated DPTIP, a potent nSMase2 inhibitor, to hydroxyl-PAMAM-dendrimer nanoparticles that can improve brain delivery. We showed that dendrimer-conjugated DPTIP (D-DPTIP) robustly inhibited the spread of pTau in an AAV-pTau propagation model. To further evaluate its efficacy, we tested D-DPTIP in the PS19 transgenic mouse model. Unexpectantly, D-DPTIP showed no beneficial effect. To understand this discrepancy, we assessed D-DPTIP's brain localization. Using immunofluorescence and fluorescence-activated cell-sorting, D-DPTIP was found to be primarily internalized by microglia, where it selectively inhibited microglial nSMase2 activity with no effect on other cell types. Furthermore, D-DPTIP inhibited microglia-derived EV release into plasma without affecting other brain-derived EVs. We hypothesize that microglial targeting allowed D-DPTIP to inhibit tau propagation in the AAV-hTau model, where microglial EVs play a central role in propagation. However, in PS19 mice, where tau propagation is independent of microglial EVs, it had a limited effect. Our findings confirm microglial targeting with hydroxyl-PAMAM dendrimers and highlight the importance of understanding cell-specific mechanisms when designing targeted AD therapies.

Inhibiting tau-induced elevated nSMase2 activity and ceramides is therapeutic in murine Alzheimer's disease.

Background: Cognitive decline in Alzheimer's disease (AD) is associated with prion-like tau propagation between neurons along synaptically connected networks, in part via extracellular vesicles (EV). EV biogenesis is triggered by ceramide enrichment at the plasma membrane from neutral sphingomyelinase2(nSMase2)-mediated cleavage of sphingomyelin. We report, for the first time, that tau expression triggers an elevation in brain ceramides and nSMase2 activity. Methods: To determine the therapeutic benefit of inhibiting this elevation, we evaluated the efficacy of PDDC, the first potent, selective, orally bioavailable, and brain-penetrable nSMase2 inhibitor, in the PS19 tau transgenic AD murine model. Changes in brain ceramide and sphingomyelin levels, Tau content, histopathology, and nSMase2 target engagement were monitored, as well as changes in the number of brain-derived EVs in plasma and their Tau content. Additionally, we evaluated the ability of PDDC to impede tau propagation in a murine model where an adeno-associated virus(AAV) encoding for P301L/S320F double mutant human tau was stereotaxically-injected unilaterally into the hippocampus and the contralateral transfer to the dentate gyrus was monitored. Results: Similar to human AD, PS19 mice exhibited increased brain ceramides and nSMase2 activity; both were completely normalized by PDDC treatment. PS19 mice exhibited elevated tau immunostaining, thinning of hippocampal neuronal cell layers, increased mossy fiber synaptophysin immunostaining, and glial activation, all pathologic features of human AD. PDDC treatment significantly attenuated these aberrant changes. Mouse plasma isolated from PDDC-treated PS19 mice exhibited reduced levels of neuron- and microglia-derived EVs, the former carrying lower phosphorylated Tau(pTau) levels, compared to untreated mice. In the AAV tau propagation model, PDDC normalized the tau-induced increase in brain ceramides and significantly decreased tau spreading to the contralateral side. Conclusions: PDDC is a first-in-class therapeutic candidate that normalizes elevated brain ceramides and nSMase2 activity leading to the slowing of tau spread in AD mice.

Inhibiting tau-induced elevated nSMase2 activity and ceramides is therapeutic in an Alzheimer's disease mouse model.

BACKGROUND: Cognitive decline in Alzheimer's disease (AD) is associated with hyperphosphorylated tau (pTau) propagation between neurons along synaptically connected networks, in part via extracellular vesicles (EVs). EV biogenesis is triggered by ceramide enrichment at the plasma membrane from neutral sphingomyelinase2 (nSMase2)-mediated cleavage of sphingomyelin. We report, for the first time, that human tau expression elevates brain ceramides and nSMase2 activity. METHODS: To determine the therapeutic benefit of inhibiting this elevation, we evaluated PDDC, the first potent, selective, orally bioavailable, and brain-penetrable nSMase2 inhibitor in the transgenic PS19 AD mouse model. Additionally, we directly evaluated the effect of PDDC on tau propagation in a mouse model where an adeno-associated virus (AAV) encoding P301L/S320F double mutant human tau was stereotaxically-injected unilaterally into the hippocampus. The contralateral transfer of the double mutant human tau to the dentate gyrus was monitored. We examined ceramide levels, histopathological changes, and pTau content within EVs isolated from the mouse plasma. RESULTS: Similar to human AD, the PS19 mice exhibited increased brain ceramide levels and nSMase2 activity; both were completely normalized by PDDC treatment. The PS19 mice also exhibited elevated tau immunostaining, thinning of hippocampal neuronal cell layers, increased mossy fiber synaptophysin immunostaining, and glial activation, all of which were pathologic features of human AD. PDDC treatment reduced these changes. The plasma of PDDC-treated PS19 mice had reduced levels of neuronal- and microglial-derived EVs, the former carrying lower pTau levels, compared to untreated mice. In the tau propagation model, PDDC normalized the tau-induced increase in brain ceramides and significantly reduced the amount of tau propagation to the contralateral side. CONCLUSIONS: PDDC is a first-in-class therapeutic candidate that normalizes elevated brain ceramides and nSMase2 activity, leading to the slowing of tau spread in AD mice.

A Semiautomated Deep Learning Approach for Pancreas Segmentation.

Accurate pancreas segmentation from 3D CT volumes is important for pancreas diseases therapy. It is challenging to accurately delineate the pancreas due to the poor intensity contrast and intrinsic large variations in volume, shape, and location. In this paper, we propose a semiautomated deformable U-Net, i.e., DUNet for the pancreas segmentation. The key innovation of our proposed method is a deformable convolution module, which adaptively adds learned offsets to each sampling position of 2D convolutional kernel to enhance feature representation. Combining deformable convolution module with U-Net enables our DUNet to flexibly capture pancreatic features and improve the geometric modeling capability of U-Net. Moreover, a nonlinear Dice-based loss function is designed to tackle the class-imbalanced problem in the pancreas segmentation. Experimental results show that our proposed method outperforms all comparison methods on the same NIH dataset.

Overexpression of KIAA1199 is an independent prognostic marker in laryngeal squamous cell carcinoma.

BACKGROUND: KIAA1199 is a recently identified novel gene that is upregulated in various human cancers with poor survival, but its role and the underlying mechanisms in laryngeal squamous cell carcinoma (LSCC) remain unknown. Here, we collected tissues from 105 cases of LSCC to investigate the relationships between KIAA1199 protein expression and clinical factors. METHODS: Western blotting and real-time quantitative PCR (RT-PCR) were used for detect the protein and mRNA expression of KIAA1199 in LSCC tissue. Immunohistochemistry (IHC) staining was used to detect the expression of KIAA1199. Patient clinical information, for instance sex, age, pathological differentiation, clinical region, T stage, N stage, clinical stage, operation type, neck lymph dissection, smoking status, and drinking status were recorded. Kaplan-Meier survival analysis and Cox analysis were applied to identify the relationship between KIAA1199 and LSCC. RESULTS: Western blotting results showed KIAA1199 protein was significantly higher in tumor tissues vs. adjacent non-cancerous tissues (0.9385 ± 0.1363 vs. 1.838 ± 0.3209, P = 0.04). The KIAA1199 mRNA expression was considerably higher in tumor tissues (P < 0.001) than in adjacent non-cancerous tissues by RT-PCR. IHC results showed up-regulated KIAA1199 expression was related with some severe clinicopathological parameters: pathologic differentiation (P = 0.002), T stage (P < 0.001), N stage (P < 0.001), clinical stage (P < 0.001), survival time (P = 0.008) and survival status (P < 0.001). Kaplan-Meier survival analysis showed that patients with high KIAA1199 protein expression had poor overall survival (OS) (P < 0.05). Cox analysis suggested that the KIAA1199 protein expression constituted an independent prognostic marker for LSCC patients (P < 0.001). CONCLUSION: Our findings revealed that KIAA1199 protein expression may be used to predict LSCC patient outcome.

Network analysis of the progranulin-deficient mouse brain proteome reveals pathogenic mechanisms shared in human frontotemporal dementia caused by GRN mutations.

Heterozygous, loss-of-function mutations in the granulin gene (GRN) encoding progranulin (PGRN) are a common cause of frontotemporal dementia (FTD). Homozygous GRN mutations cause neuronal ceroid lipofuscinosis-11 (CLN11), a lysosome storage disease. PGRN is a secreted glycoprotein that can be proteolytically cleaved into seven bioactive 6 kDa granulins. However, it is unclear how deficiency of PGRN and granulins causes neurodegeneration. To gain insight into the mechanisms of FTD pathogenesis, we utilized Tandem Mass Tag isobaric labeling mass spectrometry to perform an unbiased quantitative proteomic analysis of whole-brain tissue from wild type (Grn+/+) and Grn knockout (Grn-/-) mice at 3- and 19-months of age. At 3-months lysosomal proteins (i.e. Gns, Scarb2, Hexb) are selectively increased indicating lysosomal dysfunction is an early consequence of PGRN deficiency. Additionally, proteins involved in lipid metabolism (Acly, Apoc3, Asah1, Gpld1, Ppt1, and Naaa) are decreased; suggesting lysosomal degradation of lipids may be impaired in the Grn-/- brain. Systems biology using weighted correlation network analysis (WGCNA) of the Grn-/- brain proteome identified 26 modules of highly co-expressed proteins. Three modules strongly correlated to Grn deficiency and were enriched with lysosomal proteins (Gpnmb, CtsD, CtsZ, and Tpp1) and inflammatory proteins (Lgals3, GFAP, CD44, S100a, and C1qa). We find that lysosomal dysregulation is exacerbated with age in the Grn-/- mouse brain leading to neuroinflammation, synaptic loss, and decreased markers of oligodendrocytes, myelin, and neurons. In particular, GPNMB and LGALS3 (galectin-3) were upregulated by microglia and elevated in FTD-GRN brain samples, indicating common pathogenic pathways are dysregulated in human FTD cases and Grn-/- mice. GPNMB levels were significantly increased in the cerebrospinal fluid of FTD-GRN patients, but not in MAPT or C9orf72 carriers, suggesting GPNMB could be a biomarker specific to FTD-GRN to monitor disease onset, progression, and drug response. Our findings support the idea that insufficiency of PGRN and granulins in humans causes neurodegeneration through lysosomal dysfunction, defects in autophagy, and neuroinflammation, which could be targeted to develop effective therapies.

Molecular Signatures of Neuroinflammation Induced by αSynuclein Aggregates in Microglial Cells.

Alpha-synuclein (αSynAgg) are pathological hallmarks of Parkinson's disease (PD) and other synucleinopathies that induce microglial activation and immune-mediated neurotoxicity, but the molecular mechanisms of αSynAgg-induced immune activation are poorly defined. We performed quantitative proteomics by mass spectrometry coupled with PCR, immunohistochemical and functional validations studies to define the molecular characteristics of alpha synuclein mediated microglial activation. In mouse microglia, αSynAgg induced robust pro-inflammatory activation (increased expression of 864 genes including Irg1, Ifit1, and Pyhin) and increased nuclear proteins involved in RNA synthesis, splicing, and anti-viral defense mechanisms. Conversely, αSynAgg decreased expression several proteins (including Cdc123, Sod1, and Grn), which were predominantly cytosolic and involved in metabolic, proteasomal and lysosomal mechanisms. Pathway analyses and confirmatory in vitro studies suggested that αSynAgg partly mediates its effects via Stat3 activation. As predicted by our proteomic findings, we verified that αSynAgg induces mitochondrial dysfunction in microglia. Twenty-six proteins differentially expressed by αSynAgg were also identified as PD risk genes in genome-wide association studies (upregulated: Brd2, Clk1, Siglec1; down-regulated: Memo1, Arhgap18, Fyn, and Pgrn/Grn). We validated progranulin (PGRN) as a lysosomal PD-associated protein that is downregulated by αSynAgg in microglia in-vivo and is expressed by microglia in post-mortem PD brain, congruent with our in vitro findings. Conclusion: Together, proteomics approach both reveals novel molecular insights into αSyn-mediated neuroinflammation in PD and other synucleinopathies.

Curcumin suppresses gastric cancer biological activity by regulation of miRNA-21: an in vitro study.

OBJECTIVE: The aim of this study was to explain the effects of curcumin to depress gastric cancer biological activity by regulation miRNA-21 an in in vitro study. METHODS: Collecting 30 pairs of adjacent and cancer tissues to measure miRNA-21 expression by ISH, evaluating pathology by H&E staining and measuring PTEN protein expression by IHC. Evaluating curcumin anti-tumor and correlation between curcumin and miRNA-21 in gastric cancer cell line (AGS) biological activities by CCK-8, flow cytometry, transwell, scratch test, transmission electron microscope, and western blot. RESULTS: Compared with adjacent normal tissues, the miRNA-21 and PTEN expressions of gastric cancer tissues were significantly different (P < 0.001, respectively). By cell experiments, compared with NC group, the AGS cell proliferation was significantly depressed with significantly increasing cell apoptosis by keeping cell cycle in G1 phase (P < 0.001, respectively), and AGS cell invasion and migration were significantly down-regulated (P < 0.001, respectively) in Cur and Cur+BL groups. However, with miRNA-21 supplementation, the AGS cell biological activities were significantly recovered (P < 0.001, respectively). By western blot, compared with the NC group, the PTEN and P21 proteins expressions were significantly up-regulated (P < 0.001, respectively) and the PI3K, AKT, MMP-2 and MMP-9 proteins expressions were significantly down-regulated (P < 0.001, respectively). PTEN, PI3K, AKT, P21, MMP-2 and MMP-9 proteins were significantly decreased with miRNA-21 supplementation (P < 0.001, respectively). CONCLUSION: Curcumin had anti-tumor effects to gastric cancer via ion of miRNA-21 by regulation of the PTEN/PI3K/AKT pathway.

Phochrodines A-D, first naturally occurring new chromenopyridines from mangrove entophytic fungus Phomopsis sp. 33.

Four new chromenopyridine derivatives, phochrodines A-D (1-4), were identified from mangrove entophytic fungus Phomopsis sp. 33# by means of various modern chromatographic, spectroscopic and single crystal X-ray diffraction techniques. Compounds 1-4 with an unusual 5H-chromeno[4,3-b]pyridine skeleton were the first naturally occurring chromenopyridines. Their anti-inflammatory, antioxidant and cytotoxic activities were evaluated. 3 and 4 showed moderate inhibition of nitric oxide production with IC50 values of 49.0 as well as 51.0µM, respectively. 4 had well ability to scavenge DPPH radical with IC50 value of 34.0µM. The four had no cytotoxic activity for MDA-MB-435 breast cancer cells.

[Hyperlipidemia inhibited inflammatory response to Porphyromonas gingivalis in apolipoprotein E knockout mice].

PURPOSE: To investigate the effect and mechanism of hyperlipidemia on inflammatory response to Porphyromonas gingivalis(P. gingivalis) in apolipoprotein E knock out(ApoE-/-) mice. METHODS: Long term hyperlipidemia model was established in ApoE-/- mice, and viable P. gingivalis were injected into peritoneal cavity to make peritonitis model. Bacteria clearance capability was detected by serial dilution, production of pro-inflammatory cytokine interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) in serum was measured by ELISA, and IL-6 as well as MCP-1 transcription in peritoneal cells was determined by real time PCR. The data was analyzed with SPSS13.0 software package. RESULTS: Hyperlipidemia disrupted P. gingivalis clearance capability in ApoE-/- mice, accompanied by inhibited IL-6 and MCP-1 transcription in peritoneal cells and decreased IL-6 and MCP-1 release into blood. CONCLUSIONS: Hyperlipidemia disrupts inflammatory response to P. gingivalis, leading to decreased bacteria clearance, which may affect periodontitis progression.