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Objective: To evaluate the effect of postoperative condylar axis changes on mandibular condylar remodeling by comparing the condylar head in three-dimensional (3D) surface reconstructions before and after surgery in skeletal Class III deformities (one-jaw [mandibular setback] or two-jaw surgery), and also to determine the relationship between condylar inward rotation and condylar surface remodeling after orthognathic surgery. Materials and Methods: A retrospective analysis was conducted of 30 patients with skeletal Class III deformities who had received orthognathic surgery. Group 1 underwent one-jaw surgery (10 men, five women, age 22.4 ± 3.3 years), and group 2 underwent two-jaw surgery (10 men, five women, age 22.3 ± 2.2 years). Sixty condyles were reconstructed and superimposed pre- and postoperatively to compare the changes of condylar surfaces. The relation between the condylar axis change and the surface change using the Pearson correlation were investigated from the 3D image software. Materials and Methods: A retrospective analysis was conducted of 30 patients with skeletal Class III deformities who had received orthognathic surgery. Group 1 underwent one-jaw surgery (10 men, five women, age 22.4 ± 3.3 years), and group 2 underwent two-jaw surgery (10 men, five women, age 22.3 ± 2.2 years). Sixty condyles were reconstructed and superimposed pre- and postoperatively to compare the changes of condylar surfaces. The relation between the condylar axis change and the surface change using the Pearson correlation were investigated from the 3D image software. Conclusion: After orthognathic surgery, condylar surface changes occurred, and condylar inward rotation was closely related to changes of condylar surface. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the influence of vermilion height on the assessment of lip attractiveness by Japanese and Korean orthodontists and orthodontic patients. Materials and Methods: Vermilion heights were modified by increasing or decreasing the vermilion height in 1.0-mm increments from -3.0 mm to 3.0 mm with reference to an average vermilion height. Participants ranged from 15 to 29 years of age and comprised 29 Japanese and 25 Korean orthodontists and 96 Japanese and 72 Korean orthodontic patients. They all rated the attractiveness of seven images with altered vermilion height using a visual analog scale. Results: Across the participant groups, there were significant differences in the median esthetic scores for the seven vermilion height levels tested. The Japanese and Korean raters assigned the highest scores to the average vermilion height and assigned the lowest scores to the +3-mm increased vermilion height. The ranges of vermilion height preferred by orthodontists were found to be within the ranges preferred by orthodontic patients when evaluating the preferences in lip esthetics by country. Conclusions: We conclude that the -1-mm to +1-mm range for the average vermilion height is considered attractive for lips for both Japanese and Korean people. [ABSTRACT FROM AUTHOR]

Objective: In this study, we aimed to examine the relationship between chin deviation and the positional and morphological features of the mandible and to determine the factors that contributed to chin deviation in individuals with a unilateral cleft lip and palate (UCLP). Methods: Cone-beam computed tomography (CBCT) images of 28 adults with UCLP were analyzed in this study. Segmented three-dimensional temporomandibular fossa and mandible images were reconstructed, and angular, linear, and volumetric parameters were measured. Results: For all 28 individuals, the chin was found to deviate to the cleft side by 1.59 mm. Moreover, among these 28 individuals, only 7 showed distinct (more than 4 mm) chin deviation, which was toward the cleft side. Compared to the non-cleft side, the mandibular body length, frontal ramal inclination, and vertical position of the condyle were lower and inclination of the temporomandibular fossa was steeper on the cleft side. Furthermore, the differences in inclination of the temporomandibular fossa, mandibular body length, ramus length, and condylar volume ratio (non-deviated/deviated) were positively correlated with chin deviation. Conclusions: UCLP individuals show mild chin deviation to the cleft side. Statistical differences were noted in the parameters that represented positional and morphological asymmetries of the mandible and temporomandibular fossa; however, these differences were too small to indicate clinical significance. [ABSTRACT FROM AUTHOR]

Objective: To compare three-dimensionally the midfacial hard- and soft-tissue asymmetries between the affected and the unaffected sides and determine the relationship between the hard tissue and the overlying soft tissue in patients with nonsyndromic complete unilateral cleft lip and palate (UCLP) by conebeam computed tomography (CBCT) analysis. Methods: The maxillofacial regions of 26 adults (18 men, 8 women) with nonsyndromic UCLP were scanned by CBCT and reconstructed by three-dimensional dental imaging. The frontalview midfacial analysis was based on a 3 x 3 grid of vertical and horizontal lines and their intersecting points. Two additional points were used for assessing the dentoalveolar area. Linear and surface measurements from three reference planes (Basion-perpendicular, midsagittal reference, and Frankfurt horizontal planes) to the intersecting points were used to evaluate the anteroposterior, transverse, and vertical asymmetries as well as convexity or concavity. Results: Anteroposteriorly, the soft tissue in the nasolabial and dentoalveolar regions was significantly thicker and positioned more anteriorly on the affected side than on the unaffected side (p < 0.05). The hard tissue in the dentoalveolar region was significantly retruded on the affected side compared with the unaffected side (p < 0.05). The other midfacial regions showed no significant differences. Conclusions: With the exception of the nasolabial and dentoalveolar regions, no distinctive midfacial hard- and soft-tissue asymmetries exist between the affected and the unaffected sides in patients with nonsyndromic UCLP. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate the isolation and characterization of multipotent human periodontal ligament (PDL) stem cells and to assess their ability to differentiate into bone, cartilage, and adipose tissue. Methods: PDL stem cells were isolated from 7 extracted human premolar teeth. Human PDL cells were expanded in culture, stained using anti-CD29, -CD34, -CD44, and -STRO-1 antibodies, and sorted by fluorescent activated cell sorting (FACS). Gingival fibroblasts (GFs) served as a positive control. PDL stem cells and GFs were cultured using standard conditions conducive for osteogenic, chondrogenic, or adipogenic differentiation. Results: An average of 152.8 ± 27.6 colony-forming units was present at day 7 in cultures of PDL stem cells. At day 4, PDL stem cells exhibited a significant increase in proliferation (p < 0.05), reaching nearly double the proliferation rate of GFs. About 5.6 _ 4.5% of cells in human PDL tissues were strongly STRO-1-positive. In osteogenic cultures, calcium nodules were observed by day 21 in PDL stem cells, which showed more intense calcium staining than GF cultures. In adipogenic cultures, both cell populations showed positive Oil Red O staining by day 21. Additionally, in chondrogenic cultures, PDL stem cells expressed collagen type II by day 21. Conclusions: The PDL contains multipotent stem cells that have the potential to differentiate into osteoblasts, chondrocytes, and adipocytes. This adult PDL stem cell population can be utilized as potential sources of PDL in tissue engineering applications. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) have a unique ability to survive in extreme acidic environments and to colonize the gastric mucosa. It can cause diverse gastric diseases such as peptic ulcers, chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, gastric cancer, etc. Based on genomic research of H. pylori, over 1600 genes have been functionally identified so far. However, H. pylori possess some genes that are uncharacterized since: (i) the gene sequences are quite new; (ii) the function of genes have not been characterized in any other bacterial systems; and (iii) sometimes, the protein that is classified into a known protein based on the sequence homology shows some functional ambiguity, which raises questions about the function of the protein produced in H. pylori. Thus, there are still a lot of genes to be biologically or biochemically characterized to understand the whole picture of gene functions in the bacteria. In this regard, knowledge on the 3D structure of a protein, especially unknown or hypothetical protein, is frequently useful to elucidate the structure-function relationship of the uncharacterized gene product. That is, a structural comparison with known proteins provides valuable information to help predict the cellular functions of hypothetical proteins. Here, we show the 3D structures of some hypothetical proteins determined by NMR spectroscopy and X-ray crystallography as a part of the structural genomics of H. pylori. In addition, we show some successful approaches of elucidating the function of unknown proteins based on their structural information. [ABSTRACT FROM AUTHOR]

Objective: Facial asymmetry is usually evaluated from the difference in length and angulation of the maxilla and mandible. However, asymmetric position or shape of the condyle can also affect the expression of asymmetry. The purpose of this study was to evaluate the correlation between condylar asymmetry and chin point deviation in facial asymmetry. Methods: Cone-beam CT images of fifty adult skeletal Class III patients were studied. Thirty patients who had more than 4 mm menton deviation were categorized in the asymmetric group. Twenty patients with less than 4 mm menton deviation were assigned to the symmetric group. Anteroposterior and transverse condyle positions were evaluated from the cranial base. The greatest mediolateral diameter (GMD) of the condyle in the axial plane and angulation to the coronal plane were measured. The height and volume of the condyles were evaluated. Results: The symmetric group had no statistical difference between both condyles in position, angulation, GMD, height and volume. In the asymmetric group, the non-deviated side condyle was larger in GMD, height and volume than the deviated side. There was no statistical difference in condyle position and angulation. The GMD, height difference and condylar volume ratio (non-deviated/deviated) were positively correlated with chin deviation. From the linear regression analysis, condylar volume ratio was a significant factor affecting chin deviation. Conclusions: These findings suggests that the non-deviated side condyle is larger than the deviated side. In addition, condylar asymmetry can affect the expression of facial asymmetry. (Korean J Orthod 2011;41(2):87-97) [ABSTRACT FROM AUTHOR]

The metal-ligand complexes, [Ru(bpy)(dppz)] (bpy = 2,2′-bipyridine, dppz = dipyrido[3,2-a:2′,3′-c]phenazine) (RuBD) and [Ru(phen)(dppz)] (phen = 1,10-phenanthroline) (RuPD), display favorable photophysical properties including long lifetime, polarized emission, and very little background fluorescence. To check if RuBD and RuPD reflect the overall rotational mobility of small nucleic acid, we measured the intensity and anisotropy decays of RuBD and RuPD when intercalated into tRNA using pBC SK(+) phagemid as a control. We used frequency-domain fluorometry with a blue light-emitting diode (LED) as the modulated light source. We observed shorter lifetimes for tRNA than those for the pBC SK(+) phagemid for both probes, however, RuPD showed much larger decrease in the mean lifetime values (64%). The slow rotational correlation time of RuBD (31.3 ns) and the fast rotational correlation time of RuPD (26.0 ns) reflected the overall rotational mobility of tRNA. In addition, the steady-state anisotropy and time-resolved anisotropy decay data showed a clear difference between tRNA and pBC SK(+) phagemid. This suggests the possibility of a homogeneous assay for identifying target nucleic acids and/or nucleic acid binding proteins. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate the effect of tribochemical silica coating on the shear bond strength (SBS) of rebonded ceramic brackets using nano-filled flowable composite resin. Methods: A total of 60 premolars were prepared and divided into 4 equal groups as follows: Tribochemical silica coating (TC) + Transbond XT (XT), TC + Transbond supreme LV (LV), Sandblast treatment (SA) + XT, SA + LV. Treated ceramic brackets were rebonded on the premolars using each adhesive. All samples were tested in shear mode on a universal testing machine. Results: SBS of silica coated groups were high enough for clinical usage (TCLV: 10.82 ± 1.82 MPa, TCXT: 11.50 ± 1.72 MPa). But, SBS of the sandblast treated groups had significantly lower values than the tribochemical silica coated groups (SALV, 1.23 ± 1.16 MPa; SAXT, 1.76 ± 1.39 MPa; p < 0.05). There was no difference between the shear bond strength by type of adhesive. In the silica coated groups, 77% of the samples showed bonding failure in the adhesive. In the sandblast treated group, all bonding failures occurred at the bracket-adhesive interface. Conclusions: The result of this study suggest that newly introduced nano-filled flowable composite resin and tribochemical silica coating application on debonded ceramic bracket bases can produce appropriate bond strengths for orthodontic bonding. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of low-level laser (LLL) irradiation on the turnover of fibronectin and collagen type I in periodontal tissue during tooth movement in rats by immunohistochemistry. Thirty male Sprague-Dawley rats aged 15 weeks were assigned to either an experimental group (n = 15) that underwent LLL irradiation during tooth movement, or a control group (n = 15). In the experimental group, the gallium-aluminum-arsenide (Ga-Al-As) diode LLL (wavelength 808 nm; output 96 mW) was used to irradiate three areas on both the palatal side and the labial side of the maxillary incisor. The radiation was administered by the contact method for 10 s at 0.83 J/cm(2) energy dose, once a day for 7 days. Total energy dose over the complete schedule was 34.86 J/cm(2). The animals were killed on days 1, 3, 7, 14 and 21. There was no difference between the two groups in the amount of tooth movement. The immunohistochemistry results showed that the expression of fibronectin and collagen type I in the experimental group had significantly increased from day 1, with a more even distribution than in the control group, and that this difference was maintained until the end of the experiment. These results suggest that LLL irradiation facilitates the reorganization of the connective tissues during tooth movement in rats. [ABSTRACT FROM AUTHOR]

The present study tested the shear bond strength (SBS) of orthodontic brackets bonded to teeth using flowable resins. A total of 105 human teeth were divided into seven groups. The brackets in each group were bonded to the tooth substrates using a Transbond XT adhesive and six other different flowable resins, respectively. Each adhesive resin was light-cured using a quartz-tungsten-halogen (QTH) light for 40 seconds. The brackets were debonded in shear mode using a universal testing machine. The brackets bonded using Tetric Flow and Grandio Flow showed slightly greater SBS values (13.0±1.8 and 12.2±1.2 MPa, respectively) than the Transbond XT adhesive (12.1±1.2 MPa). However, the SBS values of Transbond XT, X-flow, Tetric Flow, Grandio Flow, and Filtek Z350 flow were not significantly different. As for Admira Flow and Aelite Flow, they scored significantly lower SBS values (7.0±2.1 and 9.2±1.3 MPa, respectively) than the other groups. On bracket failure mode, statistical analysis revealed a similar failure mode among all the seven test groups. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate the effect of thermocycling and type of porcelain restoration on shear bond strength (SBS) and mode of failure of monocrystalline ceramic brackets. Methods: A total of 60 porcelain discs were made and divided into three equal groups as follows: Ceramco 3, IPS Empress II, Zi-ceram/Vintage ZR. ceramic brackets were bonded to the prepared porcelain surfaces in the same manner. Each group was divided randomly into two subgroups: thermocycled group and non-thermocycled group (control). All samples were tested in shear mode on an universal testing machine. Results: SBS of the non-thermocycled group was clinically acceptable (Ceramco 3: 7.06 ± 1.76 MPa, IPS Empress II: 7.55 ± 2.38 MPa, Zi-ceram/Vintage ZR: 7.19 ± 1.38 MPa). But, SBS of the thermocycled group was significantly reduced (Ceramco 3: 4.88 ± 1.00 MPa, IPS Empress II: 5.46 ± 1.35 MPa, Zi-ceram/Vintage ZR: 4.84 ± 1.01 MPa, p < 0.05). There was no difference between the shear bond strength by type of porcelain restoration. All bonding failure occurred between bracket base and adhesive, except for 2 samples. Conclusions: The results of this study suggest that the type of porcelain restoration did not affect SBS, but thermocycling weakened SBS. Therefore, the effect of thermocycling should be considered when using ceramic brackets in practice. [ABSTRACT FROM AUTHOR]

Tooth anklylosis is defined as the adhesion state of alveolar bone to dentin or cementum. Trauma, disturbed metabolic disease, and congenital disease have been given as etiologic factors. Complications of tooth ankylosis are tipping of the neighboring teeth, space loss, and supraeruption of the opposing teeth. Particularly if dental ankylosis occurs in maxillary incisors of a growing child, the ankylosed tooth can not move vertically with subsequent disturbance in vertical growth of the alveolar process. With an appropriate treatment approach, an esthetic condition must be achieved especially in the maxillary anterior region. In this report, two cases are presented which were treated by the surgical repositioning method. One is treated by alveolar bone distraction osteogenesis which used a tooth-borne type distraction device and the other by single tooth osteotomy. [ABSTRACT FROM AUTHOR]

Objective: CBCT has become popular for orthodontic diagnosis and treatment planning in recent times. The 3D pharyngeal airway space needs to be analysed using a 3D diagnostic tool. The aim of this study was to analyse the pharyngeal airway of different craniofacial morphology using CBCT. Methods: The sample compromised 102 subjects divided into 3 groups (Class I, II, III) and 6 subgroups according to normal or vertical craniofacial patterns. All samples had CBCT (VCT, Vatech, Seoul, Korea) taken for orthodontic treatment. The pharyngeal airway was assessed according to the reference planes: aa plane (the most anterior point on the anterior arch of atlas), CV2 plane, and CV3 plane (most infero-anterior point on the body of the second & third cervical vertebra). The intergroup comparison was performed with one-way ANOVA and duncan test as a second step. Results: The results showed the pharyngeal airway and anteroposterior width of group 2 (Class II) in aa plane, CV2 plane, CV3 plane were significant narrower than in group 3 (Class III). There was no significant difference between vertical and normal craniofacial patterns except for the anteroposterior pharyngeal width of Group 1 (Class I) in aa plane. Conclusions: Subjects with Class II patterns have a significantly narrower pharyngeal airway than those with Class III. However there was no difference in pharyngeal airway between vertical and normal craniofacial morphology. [ABSTRACT FROM AUTHOR]

This study assessed the effect of acetic NaF solutions on stainless steel orthodontic brackets. Acetic acid was added to a 0.1% NaF solution to make two solutions, one with pH 3.5 and the other with pH 6. For the two different stainless steel brackets (Tomy, Dentaurum) used in this study, they had a similar elemental composition-except with Mo (molybdenum) in the Tomy bracket. The brackets were then immersed in the prepared test solutions for three days and their responses evaluated. In terms of hydrofluoric acid (HF) concentration, the 0.1%/ pH 3.5 solution showed a high HF concentration at 227 ppm, while that of 0.1%/ pH 6 solution was very low at 7 ppm. In terms of color change and element release, only the Dentaurum brackets in 0.1%/ pH 3.5 solution showed an appreciable color change (ΔE*=4.0) and released a great amount of elements (Fe, Cr, Ni, Mn) after three days. Otherwise, regardless of pH value and product, only minor color change (ΔE*<1.0) and negligible element release occurred. In terms of surface modification, no visible changes in surface morphology were observed in any product after immersion in test solutions. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus type 1 (HIV-1) integrase is an essential enzyme in the life cycle of the virus. It is responsible for catalyzing the insertion of the viral genome into the host cell chromosome. This integrase is an attractive target for the design of a HIV antiviral drug, because integrase has no human counterpart. In order to know the interaction mode of HIV-1 integrase with its inhibitor, we investigated the effect of the inhibitor, baicalein, on the conformation of the HIV-1 integrase catalytic domain [IN-(50- 212/F185K)] using fluorescence and circular dichroism (CD) spectroscopy. We found that baicalein binds to the hydrophobic region of the HIV-1 integrase catalytic core domain. This binding of baicalein induces the conformational change of the enzyme. We also found that the binding ratio of baicalein to the HIV-1 integrase catalytic domain is 2:1. [ABSTRACT FROM AUTHOR]

Purpose: To test the bonding of orthodontic brackets to teeth using a diode-pumped solid state (DPSS) laser. Methods: A total of 60 extracted human teeth were divided randomly into four groups: Group 1 (control) - the brackets were bonded to teeth using the quartz-tungsten-halogen (QTH) light (800 mW/cm²) for 40 seconds; Groups 2-4 - the brackets were bonded to teeth using the DPSS laser (500 mW/cm²) for 40 seconds, 20 seconds, and 10 seconds, respectively. The teeth were debonded using shear force in a universal testing machine, and the amount of residual adhesive remaining on each tooth was evaluated. Statistical analysis was carried out for the shear bond strength (SBS) and Adhesive Renmant Index (AR!). Results: The brackets bonded using the DPSS laser for 40 seconds showed the highest mean SBS (13.1±1.2 MPa) among the groups. Furthermore, the DPSS laser with 10 seconds light-curing could achieve 83% of the mean SBS obtained using the QTH light for 40 seconds. The ARI scores showed no differences among all four groups suggesting a similar failure mode. [ABSTRACT FROM AUTHOR]

The article discusses a research that describes the structural analysis of residual dipolar couplings (RDCs) with dipolar waves and delta maps. It states that the measurement enables the phage-induced alignment of membrane proteins. Illustration of measurements of RDCs for three different phage-aligned membrane proteins is presented.

α-Vinyl or α-acetylenyl azacycles were easily synthesized from 7- to 9-membered lactams and 6- to 9-membered lactams via N,O-acetal trimethylsilyl (TMS) ethers. Organocopper and organostannane reagents afforded reasonable yields for the respective N-acyliminium ion vinylation and acetylenylation intermediates generated from N,O-acetal TMS ethers in the presence of a Lewis acid.

The versatile synthesis of (−)-6-desmethyl-fluvirucinine A1 was accomplished at a 24% overall yield through a thirteen-step process from a known vinylpiperidine. The key part involved the elaboration of the distal stereocenters and a macrolactam skeleton via conformationally-induced diastereocontrol and the iterative aza-Claisen rearrangements of lactam precursors.

The purpose of this study was to develop a biobetter version of recombinant human interferon-β 1a (rhIFN-β 1a) to improve its biophysical properties, such as aggregation, production and stability, and pharmacokinetic properties without jeopardizing its activity. To achieve this, we introduced additional glycosylation into rhIFN-β 1a via site-directed mutagenesis. Glycoengineering of rhIFN-β 1a resulted in a new molecular entity, termed R27T, which was defined as a rhIFN-β mutein with two N-glycosylation sites at 80th (original site) and at an additional 25th amino acid due to a mutation of Thr for Arg at position 27th of rhIFN-β 1a. Glycoengineering had no effect on rhIFN-β ligand-receptor binding, as no loss of specific activity was observed. R27T showed improved stability and had a reduced propensity for aggregation and an increased half-life. Therefore, hyperglycosylated rhIFN-β could be a biobetter version of rhIFN-β 1a with a potential for use as a drug against multiple sclerosis.

Hepatitis C virus (HCV) nonstructural protein 5B (NS5B), an RNA-dependent RNA polymerase (RdRp), is the key enzyme for HCV RNA replication. We previously showed that HCV RdRp is phosphorylated by protein kinase C-related kinase 2 (PRK2). In the present study, we used biochemical and reverse-genetics approaches to demonstrate that HCV NS5B phosphorylation is crucial for viral RNA replication in cell culture. Two-dimensional phosphoamino acid analysis revealed that PRK2 phosphorylates NS5B exclusively at its serine residues in vitro and in vivo. Using in vitro kinase assays and mass spectrometry, we identified two phosphorylation sites, Ser29 and Ser42, in the 1 finger loop region that interacts with the thumb subdomain of NS5B. Colonyforming assays using drug-selectable HCV subgenomic RNA replicons revealed that preventing phosphorylation by Ala substitution at either Ser29 or Ser42 impairs HCV RNA replication. Furthermore, reverse-genetics studies using HCV infectious clones encoding phosphorylation-defective NS5B confirmed the crucial role of these PRK2 phosphorylation sites in viral RNA replication. Molecular-modeling studies predicted that the phosphorylation of NS5B stabilizes the interactions between its 1 loop and thumb subdomain, which are required for the formation of the closed conformation of NS5B known to be important for de novo RNA synthesis. Collectively, our results provide evidence that HCV NS5B phosphorylation has a positive regulatory role in HCV RNA replication. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) play important roles in normal brain development and synaptic plasticity, although aberrant expression of MMPs leads to brain damage, including blood–brain barrier disruption, inflammation, demyelination, and neuronal cell death. In this article, we report that MMP-8 is upregulated in LPS-stimulated BV2 microglial cells and primary cultured microglia, and treatment of MMP-8 inhibitor (M8I) or MMP-8 short hairpin RNA suppresses proinflammatory molecules, particularly TNF-α secretion. Subsequent experiments showed that MMP-8 exhibits TNF-α–converting enzyme (TACE) activity by cleaving the prodomain of TNF-α (A74/Q75, A76/V77 residues) and, furthermore, that M8I inhibits TACE activity more efficiently than TAPI-0, a general TACE inhibitor. Biochemical analysis of the underlying anti-inflammatory mechanisms of M8I revealed that it inhibits MAPK phosphorylation, NF-κB/AP-1 activity, and reactive oxygen species production. Further support for the proinflammatory role of microglial MMP-8 was obtained from an in vivo animal model of neuroinflammatory disorder. MMP-8 is upregulated in septic conditions, particularly in microglia. Administration of M8I or MMP-8 short hairpin RNA significantly inhibits microglial activation and expression/secretion of TNF-α in brain tissue, serum, and cerebrospinal fluid of LPS-induced septic mice. These results demonstrate that MMP-8 critically mediates microglial activation by modulating TNF-α activity, which may explain neuroinflammation in septic mouse brain. [ABSTRACT FROM AUTHOR]