Caffeic Acid Phenethyl Ester Enhances Bone Repair-related Factors in MC3T3-E1 Cells.

Apical periodontitis is an inflammatory disease caused by bacterial infection in the root canal that spreads to the apical periodontal tissues, resulting in bone resorption around the root apex as the disease progresses. Vascular endothelial growth factor (VEGF), a growth factor involved in angiogenesis, plays an important role in bone remodeling. We reported that caffeic acid phenethyl ester (CAPE), a bioactive substance of propolis, induces VEGF in odontoblast-like cells and dental pulp cells.

Effect of interleukin-17A on inflammatory mediator production in interleukin-1β-stimulated human dental pulp fibroblasts.

In response to pro-inflammatory cytokines such as interleukin (IL)-1β, dental pulp fibroblasts produce various inflammatory mediators, including IL-6, IL-8, CC chemokine ligand 20 (CCL20), and CXC chemokine ligand 10 (CXCL10), leading to the progression of pulpitis. IL-17/IL-17A (IL-17A) is a pro-inflammatory cytokine secreted by T helper (Th) 17 cells following their recruitment to inflamed sites; however, the roles of IL-17A during pulpitis remain unclear. The purpose of this study was to investigate the effect of IL-17A on IL-6, IL-8, CCL20 and CXCL10 production by human dental pulp fibroblasts (HDPFs) in vitro.

Caffeic Acid Phenethyl Ester Induces Vascular Endothelial Growth Factor Production and Inhibits CXCL10 Production in Human Dental Pulp Cells.

The survival rate of root non-vital teeth is lower than that of vital teeth. Therefore, to preserve the dental pulp is very important. The vascular endothelial growth factor (VEGF) is the most potent angiogenic factor involved in the vitality of dental pulp including reparative dentin formation.

Phase II study of tazemetostat for relapsed or refractory B-cell non-Hodgkin lymphoma with EZH2 mutation in Japan.

Tazemetostat is a selective, reversible, small-molecule inhibitor of the histone methyltransferase enzyme, enhancer of zest homolog 2 (EZH2). In this multicenter, open-label, phase II study, we assessed the efficacy and safety of tazemetostat in Japanese patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma harboring the EZH2 mutation. Tazemetostat (800 mg twice daily) was given orally (28-day cycle) until disease progression or unacceptable toxicity.

Phase 1 study of tazemetostat in Japanese patients with relapsed or refractory B-cell lymphoma.

Background: Tazemetostat is a selective and orally available inhibitor of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and epigenetic regulator of cellular differentiation programs. We carried out a phase I study of tazemetostat in Japanese patients with relapsed or refractory B-cell non-Hodgkin-type lymphoma (B-NHL) to evaluate its tolerability, safety, pharmacokinetics, and preliminary antitumor activity.

Methods: Tazemetostat was given orally at a single dose of 800 mg on the first day and 800 mg twice daily (BID: total 1600 mg/d) on following days in a 28-day/cycle manner.

Caffeic Acid Phenethyl Ester (CAPE) Induces VEGF Expression and Production in Rat Odontoblastic Cells.

Caffeic acid phenethyl ester (CAPE), the main component of propolis, has various biological activities including anti-inflammatory effect and wound healing promotion. Odontoblasts located in the outermost layer of dental pulp play crucial roles such as production of growth factors and formation of hard tissue termed reparative dentin in host defense against dental caries. In this study, we investigated the effects of CAPE on the upregulation of vascular endothelial growth factor (VEGF) and calcification activities of odontoblasts, leading to development of novel therapy for dental pulp inflammation caused by dental caries.

The roles of odontoblasts in dental pulp innate immunity.

Odontoblasts located in the outermost layer of dental pulp form a natural barrier between mineralized tissues, dentin, and soft tissues, dental pulp, of the vital tooth, and they first recognize caries-related pathogens and sense external irritations. Therefore, odontoblasts possess a specialized innate immune system to fight oral pathogens invading into dentin. Generally, the rapid initial sensing of microbial pathogens, especially pathogen-associated molecular patterns (PAMPs) shared by microorganisms, are mediated by pattern recognition receptors (PRRs), such as Toll-like receptor and the nucleotide-binding oligomerization domain (NOD).

E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma: A phase I study.

E7777, a recombinant cytotoxic fusion protein comprising diphtheria toxin fragments A and B and human interleukin-2, shares an amino acid sequence with denileukin diftitox but has improved purity and an increased percentage of active protein monomer species. A phase I study was carried out to evaluate the tolerability, safety, pharmacokinetics, and antitumor activity of E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma. E7777 (6, 12, and expanded 9 μg/kg/day) was given to 13 patients by i.

Functional Roles of NOD1 in Odontoblasts on Dental Pulp Innate Immunity.

Caries-related pathogens are first recognized by odontoblasts and induce inflammatory events that develop to pulpitis. Generally, initial sensing of microbial pathogens is mediated by pattern recognition receptors, such as Toll-like receptor and nucleotide-binding oligomerization domain (NOD); however, little is known about NODs in odontoblasts. In this study, the levels of NODs expressed in rat odontoblastic cell line, KN-3, were assessed by flow cytometry and the levels of chemokines in NOD-specific ligand-stimulated KN-3 cells were analyzed by real-time PCR and ELISA.

Phase 1 combination study of eribulin mesylate with trastuzumab for advanced or recurrent human epidermal growth factor receptor 2 positive breast cancer.

Eribulin mesylate (Halaven®) is a novel inhibitor of microtubule dynamics that has demonstrated a survival benefit in patients with locally recurrent or metastatic breast cancer who previously received at least two chemotherapeutic regimens including an anthracycline and a taxane. Although trastuzumab is indicated for patients with human epidermal growth factor receptor 2 positive (HER2+) breast cancer, a phase 1 study to evaluate tolerability/safety of eribulin mesylate with trastuzumab has not been conducted. Therefore, a study of eribulin mesylate in combination with trastuzumab was conducted to evaluate dose limiting toxicity (DLT), tolerability/safety, pharmacokinetics (PK), and efficacy and to estimate the recommended dose in Japanese patients with advanced or recurrent HER2+ breast cancer.

Modulatory roles of interferon-γ through indoleamine 2, 3-dioxygenase induction in innate immune response of dental pulp cells.

Introduction: Marked infiltration of inflammatory cells such as activated T cells producing interferon-γ (IFN-γ) is observed in severe pulpitis. However, the roles of IFN-γ in the innate immune response of dental pulp have not been reported. Indoleamine 2, 3-dioxygenase (IDO) is a regulator of immune responses, and the IDO expression is induced by IFN-γ in many cells whose expression in dental pulp is unknown.

Inhibition of matrix metalloproteinase-9 activity by doxycycline ameliorates RANK ligand-induced osteoclast differentiation in vitro and in vivo.

Tetracycline antibiotics, including doxycycli\e (DOX), have been used to treat bone resorptive diseases, partially because of their activity to suppress osteoclastogenesis induced by receptor activator of nuclear factor kappa B ligand (RANKL). However, their precise inhibitory mechanism remains unclear. Therefore, the present study examined the effect of Dox on osteoclastogenesis signaling induced by RANKL, both in vitro and in vivo.

Black tea polyphenol inhibits CXCL10 production in oncostatin M-stimulated human gingival fibroblasts.

CXC chemokine ligand 10 (CXCL10) plays an important role in the infiltration of Th1 cells and thus in the exacerbation of periodontal disease. Theaflavin-3,3'-digallate (TFDG), polyphenol in black tea, has some beneficial effects but the effect of TFDG on CXCL10 production from human gingival fibroblasts (HGFs) is uncertain. In this study, we investigated the mechanisms by which TFDG may inhibit oncostatin M (OSM)-induced CXCL10 production in human gingival fibroblasts.

Characterization of a Bombyx mori nucleopolyhedrovirus mutant lacking both fp25K and p35.

Recent studies have shown that dual mutations in fp25K and p35 of Autographa californica nucleopolyhedrovirus (AcMNPV) result in a typical apoptotic infection on Trichoplusia ni cells, suggesting the involvement of FP25K on NPV-induced apoptosis. To examine the effect of fp25K deletion on Bombyx mori NPV (BmNPV)-induced apoptosis, we generated a BmNPV mutant, fp-p35D, in which both fp25K and p35 genes are deleted from the genome, and compared its phenotype with wild-type (T3), fp25K-deleted (fp-null), and p35-deleted (p35D) BmNPVs. In BmN cells, p35D, but not T3 or fp-null, caused apoptosis with caspase-3 activation.

Anti-inflammatory effect of catechin on cultured human dental pulp cells affected by bacteria-derived factors.

Catechins (bioactive polyphenols in green tea) are known to exhibit potent anti-inflammatory properties. However, the anti-inflammatory effects of catechins on inflamed dental pulp tissue are not known. In this study, we investigated the effect of epigallocatechin-3-gallate (EGCG) and epicatechin gallate (ECG), the major components of green tea catechins, on the expression of pro-inflammatory cytokines and adhesion molecules in human dental pulp cells stimulated with bacteria-derived factors such as lipopolysaccharide (LPS) and peptidoglycan (PG).

Tea polyphenols inhibit IL-6 production in tumor necrosis factor superfamily 14-stimulated human gingival fibroblasts.

IL-6 is well recognized to be a potent bone resorptive agent and thus in the development of periodontal disease. Epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), the major catechins in green tea, and theaflavin-3,3'-digallate (TFDG), polyphenol in black tea, have multiple beneficial effects, but the effects of catechins and theaflavins on IL-6 production in human gingival fibroblasts (HGFs) are not known. In this study, we investigated the mechanisms by which EGCG, ECG, and TFDG inhibit tumor necrosis factor superfamily 14 (TNFSF14)-induced IL-6 production in HGFs.

Comparative studies of lepidopteran baculovirus-specific protein FP25K: development of a novel Bombyx mori nucleopolyhedrovirus-based vector with a modified fp25K gene.

Lepidopteran baculovirus-specific protein FP25K performs many roles during the infection cycle, including functions in the production of occlusion bodies (OBs) and budded viruses (BVs), oral infection, and postmortem host degradation. To explore the common and specific functions of FP25K proteins among lepidopteran baculoviruses, we performed comparative analyses of FP25K proteins from group I and group II nucleopolyhedroviruses (NPVs) and granulovirus (GV). Using recombinant Bombyx mori NPVs (BmNPVs), we showed that the FP25Ks from NPVs were able to eliminate all the phenotypic defects observed in an infection with a BmNPV mutant lacking functional fp25K but that FP25K from GV did not show abilities to recover oral infectivity and postmortem host degradation.

Tea catechins reduce inflammatory reactions via mitogen-activated protein kinase pathways in toll-like receptor 2 ligand-stimulated dental pulp cells.

Aims: In this study, we evaluated whether catechins could inhibit the expression of pro-inflammatory mediators induced by dental caries-related bacteria, Streptococci, or pathogen-associated molecular patterns (PAMPs) stimulation in human dental pulp fibroblasts (HDPF). We further determined the mechanisms of the anti-inflammatory activity of catechins.

Main Methods: Streptococci or PAMP-stimulated HDPF were treated with catechin, and then the expression and production of pro-inflammatory mediators were determined by RT-PCR and ELISA.

Catechins inhibit CCL20 production in IL-17A-stimulated human gingival fibroblasts.

CC chemokine ligand 20 (CCL20) plays a pivotal role in the recruitment of Th17 cells and thus in the development of periodontal disease. Epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), the major catechins in green tea, have multiple beneficial effects, but the effects of catechins on CCL20 production in human gingival fibroblasts (HGFs) are not known. In this study, we investigated the mechanisms by which EGCG and ECG inhibit interleukin (IL)-17A-induced CCL20 production in human gingival fibroblasts.

Catechins inhibit CXCL10 production from oncostatin M-stimulated human gingival fibroblasts.

CXC chemokine ligand 10 (CXCL10) plays a pivotal role in the recruitment of Th1 cells and, thus, in the development of periodontal disease. Epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), the major catechins derived from green tea, have multiple beneficial effects, but the effects of catechins on CXCL10 production from human gingival fibroblasts (HGFs) is not known. In this study, we investigated the mechanisms by which EGCG and ECG inhibit oncostatin M (OSM)-induced CXCL10 production in HGFs.

Bombyx mori nucleopolyhedrovirus FP25K is essential for maintaining a steady-state level of v-cath expression throughout the infection.

It has been previously reported that the fp25K product of Bombyx mori nucleopolyhedrovirus (BmNPV) is required for post-mortem host degradation, but the mechanism by which it regulates host degradation is still unknown. This study shows that disruption of BmNPV fp25K attenuates the expression of viral cathepsin gene (v-cath) at a late stage of infection, and thus reduces the secretion of its product V-CATH. Western blot analysis showed that secretion of V-CATH was severely reduced in BmN cells and B.

N-linked glycans located in the pro-region of Bombyx mori nucleopolyhedrovirus V-CATH are essential for the proper folding of V-CATH and V-CHIA.

Post-mortem host degradation by infection of Bombyx mori nucleopolyhedrovirus (BmNPV) requires the synergistic activation of two virus-encoded genes, cathepsin (v-cath) and chitinase (v-chiA). Previous studies have suggested that V-CHIA is essential for the proper folding of the nascent V-CATH polypeptide in the endoplasmic reticulum, and that the putative V-CHIA-V-CATH interaction might be mediated by N-linked glycans of V-CATH. Sequence analysis shows that BmNPV V-CATH includes three consensus N-linked glycosylation sites (asparagine 38, 65 and 158).

Computed tomographic air-contrast enema imaging for presurgical examination of colon tumors: assessment with colon phantoms and in patients.

Purpose: We investigated the mechanism of colon wall deformities in phantoms and assessed the relation between pathological T staging and wall deformity in patients using computed tomography (CT) enema imaging.

Materials And Methods: We performed multidetector-row CT in mass-containing phantoms with no structural deformities and in 36 patients with colon tumors. In the phantoms, we compared images on double-contrast barium (DCB) and CT enema studies, and we compared wall deformities on CT enema studies and the actual phantom structure.