• Aging
• ECM based biomaterials
• Host defense
• Single-cell RNA sequence
• Spatial transcriptomics

• Animals
• Extracellular Matrix/metabolism
• Tissue Scaffolds/chemistry
• Wound Healing
• Mice
• Macrophages/metabolism
• Aging
• Mice, Inbred C57BL
• Fibroblasts/metabolism
• Male
• Humans
• Biocompatible Materials/chemistry

• MMP inhibitors
• TIMPs
• doxycycline
• lung inflammation
• matrix metalloproteinase (MMPs)
• tuberculosis (TB)

• Humans
• Matrix Metalloproteinase Inhibitors/pharmacology
• Matrix Metalloproteinase Inhibitors/therapeutic use
• Mycobacterium tuberculosis/drug effects
• Matrix Metalloproteinases/metabolism
• Antitubercular Agents/pharmacology
• Antitubercular Agents/therapeutic use
• Animals
• Tuberculosis, Pulmonary/drug therapy
• Tuberculosis/drug therapy
• Disease Progression

• COPD
• Inflammatory cytokines
• Periodontitis
• Soft tissue destruction
• Th17 cells

Host immune responses at the site of Mycobacterium tuberculosis (Mtb) infection can mediate pathogenesis of tuberculosis (TB) and onward transmission of infection. We hypothesized that pathological immune responses would be enriched at the site of host-pathogen interactions modelled by a standardized tuberculin skin test (TST) challenge in patients with active TB compared to those without disease, and interrogated immune responses by genome-wide transcriptional profiling. We show exaggerated interleukin (IL)-17A and Th17 responses among 48 individuals with active TB compared to 191 with latent TB infection, associated with increased neutrophil recruitment and matrix metalloproteinase-1 expression, both involved in TB pathogenesis. Curative antimicrobial treatment reversed these observed changes. Increased IL-1β and IL-6 responses to mycobacterial stimulation were evident in both circulating monocytes and in molecular changes at the site of TST in individuals with active TB, supporting a model in which monocyte-derived IL-1β and IL-6 promote Th17 differentiation within tissues. Modulation of these cytokine pathways may provide a rational strategy for host-directed therapy in active TB.

• Carcinogenesis
• Colorectum
• Cytokine
• Stroma
• TH17

• IL-17A
• IL-35
• IL-6
• IL-8
• human periodontal ligament cells

• Mtb
• Host-directed therapy
• Immunopathology
• MMPs
• Signalling pathways

• Animals
• Extracellular Matrix/metabolism
• Humans
• Lung/metabolism
• Lung/pathology
• Matrix Metalloproteinases/metabolism
• Mycobacterium tuberculosis/pathogenicity
• Signal Transduction/physiology
• Tuberculosis, Pulmonary/metabolism
• Tuberculosis, Pulmonary/pathology

• No. CARS-36 China Agriculture Research System
• Project No. 2013DFG32500 MoSTRCUK International Cooperation Project
• Project No. 2017YFD0500901 National Key Research and Development Program
• Project No. GDW20151100036, GDW20161100071 High-end Foreign Experts Recruitment Program
•  Project No. 31572487, 31873005  National Natural Science Foundation of China
• China Agriculture Research System
• National Natural Science Foundation of China

• controlled release
• drug-loaded micelles
• electrospun nano-fibers
• periodontal disease
• scaffold

• Adult
• Animals
• Dogs
• Drug Carriers/chemistry
• Drug Delivery Systems
• Drug Liberation
• Gelatin/chemistry
• Humans
• Lipopolysaccharides
• Male
• Matrix Metalloproteinases/metabolism
• Micelles
• Nanofibers/chemistry
• Nanofibers/ultrastructure
• Particle Size
• Periodontal Diseases/diagnostic imaging
• Periodontal Diseases/therapy
• Periodontal Ligament/pathology
• Polyesters/chemistry
• Polyethylene Glycols/chemistry
• Toxicity Tests
• X-Ray Microtomography

• MMP
• TH-17
• immunopathology
• innate immunity
• mycobacteria

• Cells, Cultured
• Class I Phosphatidylinositol 3-Kinases/metabolism
• Enzyme Induction
• Humans
• Interleukin-17/immunology
• Interleukin-17/metabolism
• Interleukin-17/pharmacology
• Interleukins/immunology
• Interleukins/metabolism
• Lung/drug effects
• Lung/enzymology
• Lung/immunology
• Lung/microbiology
• Matrix Metalloproteinase 3/biosynthesis
• Matrix Metalloproteinase 3/genetics
• Mycobacterium tuberculosis/immunology
• Mycobacterium tuberculosis/pathogenicity
• Paracrine Communication/drug effects
• Signal Transduction/drug effects
• Stromal Cells/drug effects
• Stromal Cells/enzymology
• Stromal Cells/immunology
• Stromal Cells/microbiology
• Th17 Cells/immunology
• Th17 Cells/metabolism
• Th17 Cells/microbiology
• Tuberculosis, Pulmonary/enzymology
• Tuberculosis, Pulmonary/genetics
• Tuberculosis, Pulmonary/immunology
• p38 Mitogen-Activated Protein Kinases/metabolism
• Interleukin-22

• G0601432 Medical Research Council

This study was designed to investigate the effect of 3D TECA hydrogel on the inflammatory-induced senescence marker, and to assess the influence of the gel on the periodontal ligament fibroblasts (PDLFs) migration in wound healing in vitro. PDLFs were cultured with 20 ng/ml TNF-α to induce inflammation in the presence and absence of 50 µM 3D TECA gel for 14 d. The gel effect on the senescence maker secretory associated-β-galactosidase (SA-β-gal) activity was measured by a histochemical staining. Chromatin condensation and DNA synthesis of the cells were assessed by 4′,6-diamidino-2-phenylindole and 5-ethynyl-2′-deoxyuridine fluorescent staining respectively. For evaluating fibroblasts migration, scratch wound healing assay and Pro-Plus Imaging software were used. The activity of senescence marker, SA-β-gal, was positive in the samples with TNF-α-induced inflammation. SA-β-gal percentage is suppressed (>65%, P < 0.05) in the treated cells with TECA gel as compared to the non-treated cells. Chromatin foci were obvious in the non-treated samples. DNA synthesis was markedly recognized by the fluorescent staining in the treated compared to non-treated cultures. Scratch wound test indicated that the cells migration rate was significantly higher (14.9 µm²/h, P < 0.05) in the treated versus (11 µm²/h) for control PDLFs. The new formula of 3D TECA suppresses the inflammatory-mediated cellular senescence and enhanced fibroblasts proliferation and migration. Therefore, 3D TECA may be used as an adjunct to accelerate repair and healing of periodontal tissues.

• 3D TECA
• Cellular senescence
• Fibroblast migration
• SA-β-gal
• TNF-α

Interleukin-12 (IL-12) is a proinflammatory cytokine, and its increased level correlates with the severity of periodontitis. However, its role in the pathogenesis of tooth periapical lesions is controversial and has not been completely clarified. The present study aimed to investigate whether IL-12 affects the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human periodontal ligament fibroblasts (hPDLFs). After treatment with IL-12 for different times, real-time PCR and Western blotting were used to determine the mRNA and protein levels of MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, and TIMP-2, respectively. ELISA was applied to measure MMPs and TIMPs secretion production. The results indicated that IL-12 significantly increased the mRNA and protein expression levels of MMP-1, MMP-3, and MMP-13, but down-regulated MMP-2 and MMP-9 mRNA and protein expression in the hPDLFs. Furthermore, IL-12 (10 ng/ml) enhanced the secreted protein production of MMP-1, MMP-3, and MMP-13, and conversely lowered MMP-2 and MMP-9 secretion levels. However, IL-12 treatment did not exert a significant effect on the mRNA and protein levels of TIMP-1 and TIMP-2 and their secreted production. Additionally, IL-12 increased the phosphorylated levels of IκBα and nuclear factor-κB P65 (NF-κB P65), and promoted NF-κB P65 subunit nuclear translocation. Pretreatment with NF-κB inhibitor not only attenuated IL-12-induced IκBα and NF-κB P65 phosphorylation and inhibited NF-κB P65 subunit into nucleus, but also antagonized IL-12-mediated MMP-1, MMP-2, MMP-3, MMP-9, and MMP-13 expression in the hPDLFs. These findings indicate that NF-κB-dependent activation is possibly indispensable for IL-12-mediated MMP expression in hPDLFs.

• Interleukin-12
• Matrix metalloproteinases
• NF-kappaB
• Periodontal ligament
• Periodontitis

• interleukin-17A
• metastasis
• miR-23b
• tongue squamous cell carcinoma
• versican

• Adult
• Aged
• Binding Sites
• Carcinoma, Squamous Cell/blood
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/metabolism
• Carcinoma, Squamous Cell/secondary
• Case-Control Studies
• Cell Line, Tumor
• Cell Movement
• Female
• Gene Expression Regulation, Neoplastic
• Head and Neck Neoplasms/blood
• Head and Neck Neoplasms/genetics
• Head and Neck Neoplasms/metabolism
• Head and Neck Neoplasms/pathology
• Humans
• I-kappa B Kinase/metabolism
• Interleukin-17/blood
• Interleukin-17/metabolism
• Male
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Middle Aged
• NF-KappaB Inhibitor alpha
• Neoplasm Invasiveness
• Phosphorylation
• Promoter Regions, Genetic
• RNA Interference
• Signal Transduction
• Squamous Cell Carcinoma of Head and Neck
• Time Factors
• Tongue Neoplasms/blood
• Tongue Neoplasms/genetics
• Tongue Neoplasms/metabolism
• Tongue Neoplasms/pathology
• Transcription Factor RelA/metabolism
• Transcription, Genetic
• Transfection
• Tumor Microenvironment
• Versicans/genetics
• Versicans/metabolism

An excess of angiotensin II (Ang II) causes hypertension and vascular injury. Activation of mitogen-activated protein kinase p38 (p38-MAPK) plays a substantial role in Ang II-dependent organ damage. Recently, we showed that p38-MAPK activation regulates the pressor response to Ang II. This study evaluates the effect of chronic p38-MAPK inhibition in Ang II-dependent hypertension.

C57Bl/6J mice were infused with Ang II for 14 days and either treated with the p38-MAPK inhibitor BIRB796 (50 mg/kg/day) or the vehicle as the control. We assessed vascular function in the aorta and isolated perfused kidneys.

Chronic p38-MAPK inhibition did not alter blood pressure at the baseline, but attenuated Ang II-induced hypertension significantly (baseline: 122 ± 2 versus 119 ± 4 mmHg; Ang II: 173 ± 3 versus 155 ± 3 mmHg; p < 0.001). In addition, BIRB796 treatment improved vascular remodeling by reducing the aortic media-to-lumen ratio and decreasing the expression of the membrane metalloproteinases (MMP) MMP-1 and MMP-9. Moreover, renal vascular dysfunction induced by chronic Ang II infusion was significantly ameliorated in the BIRP796-treated mice. Acute p38-MAPK inhibition also improved vascular function in the aorta and kidneys of Ang II-treated mice, highlighting the important role of p38-MAPK activation in the pathogenesis of vascular dysfunction.

Our findings indicated there is an important role for p38-MAPK in regulating blood pressure and vascular injury, and highlighted its potential as a pharmaceutical target.

• Angiotensin II
• animal study
• blood pressure
• hypertension
• kidney
• mice
• mitogen-activated protein kinase
• vascular dysfunction

Adult or postprimary tuberculosis (TB) accounts for most TB cases. Its hallmark is pulmonary cavitation, which occurs as a result of necrosis in the lung in individuals with tuberculous pneumonia. Postprimary TB has previously been known to be associated with vascular thrombosis and delayed-type hypersensitivity, but their roles in pulmonary cavitation are unclear. A necrosis-associated extracellular cluster (NEC) refers to a cluster of drug-tolerant Mycobacterium tuberculosis attached to lysed host materials and is proposed to contribute to granulomatous TB. Here we suggest that NECs, perhaps due to big size, produce a distinct host response leading to postprimary TB. We propose that vascular thrombosis and pneumonia arise from NEC and that these processes are promoted by inflammatory cytokines produced from cell-mediated delayed-type hypersensitivity, such as interleukin-17 and gamma interferon, eventually triggering necrosis in the lung and causing cavitation. According to this view, targeting NEC represents a necessary strategy to control adult TB.

• Glioblastoma
• Invasion
• Matrix metalloproteinases
• Migration
• Naringin
• Signaling pathways

Angiogenesis has an important role in the progression of temporomandibular joint disorders (TMD). The aim of the present study was to explore the association between dickkopf-related protein 1 (DKK-1) and angiogenesis in TMD. The expression levels of DKK-1 and vascular endothelial growth factor (VEGF) were quantified by an ELISA assay of the synovial fluid from patients with TMD. The correlation between DKK-1 and VEGF was analyzed by Pearson correlation test. Synovial fibroblasts were isolated from patients with TMD and were subsequently treated with recombinant human DKK-1, anti-DKK-1 antibody, hypoxia inducible factor-1α (HIF-1α), or small interfering RNA (siRNA). The expression levels of DKK-1, HIF-1α, and VEGF were subsequently quantified. The present study also investigated the effects of DKK-1 on the migration of human umbilical vein endothelial cells (HUVEC). Increased expression levels of DKK-1 were concordant with increased expression levels of VEGF in the synovial fluid from patients with TMD. In the synovial fibroblasts, DKK-1 increased the expression levels of VEGF, and promoted HIF-1α nuclear localization. In addition, DKK-1 induced HUVEC migration, and HIF-1α siRNA inhibited DKK-1-induced cell migration. The results of the present study indicate that DKK-1 is associated with angiogenesis in the synovial fluid of patients with TMD. Furthermore, HIF-1α may be associated with DKK-1-induced HUVEC activation.

• HT-29
• IL-17
• Inflammatory bowel disease
• TNF-α

• Adaptor Proteins, Signal Transducing
• Epithelial Cells/drug effects
• Epithelial Cells/immunology
• Epithelial Cells/metabolism
• Gene Expression Regulation
• HT29 Cells
• Humans
• Inflammation Mediators/pharmacology
• Inflammatory Bowel Diseases/genetics
• Inflammatory Bowel Diseases/immunology
• Inflammatory Bowel Diseases/metabolism
• Interleukin-17/pharmacology
• Intestinal Mucosa/drug effects
• Intestinal Mucosa/immunology
• Intestinal Mucosa/metabolism
• Neutrophils/drug effects
• Neutrophils/immunology
• Neutrophils/metabolism
• Phosphorylation
• Protein Kinase Inhibitors/pharmacology
• RNA Interference
• Signal Transduction/drug effects
• Time Factors
• Transfection
• Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/genetics
• Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism
• Tumor Necrosis Factor-alpha/pharmacology
• p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors
• p38 Mitogen-Activated Protein Kinases/metabolism

• Bioactivity
• Bioceramic
• Dental pulp stem cells
• Migration
• Pulp repair

• Interleukin-17
• Osteoprotegerin
• RANK Ligand
• periodontal ligament cells
• signal transduction

Baicalein, one of the major flavonids in Scutellaria baicalensis, has historically been used in anti-inflammatory and anti-cancer therapies. However, the anti-metastatic effect and related mechanism(s) in glioma are still unclear. In this study, we thus utilized glioma cell lines U87MG and U251MG to explore the effect of baicalein. We found that administration of baicalein significantly inhibited migration and invasion of glioma cells. In addition, after treating with baicalein for 24 h, there was a decrease in the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 expression as well as proteinase activity in glioma cells. Conversely, the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 was increased in a dose-dependent manner. Moreover, baicalein treatment significantly decreased the phosphorylated level of p38, but not ERK1/2, JNK1/2 and PI3K/Akt. Combined treatment with a p38 inhibitor (SB203580) and baicalein resulted in the synergistic reduction of MMP-2 and MMP-9 expression and then increase of TIMP-1 and TIMP-2 expression; and the invasive capabilities of U87MG cells were also inhibited. However, p38 chemical activator (anisomycin) could block these effects produced by baicalein, suggesting baicalein directly downregulate the p38 signaling pathway. In conclusion, baicalein inhibits glioma cells invasion and metastasis by reducing cell motility and migration via suppression of p38 signaling pathway, suggesting that baicalein is a potential therapeutic agent for glioma.

• Anisomycin/pharmacology
• Antineoplastic Agents, Phytogenic/isolation & purification
• Antineoplastic Agents, Phytogenic/pharmacology
• Cell Line, Tumor
• Cell Movement/drug effects
• Drug Synergism
• Flavanones/antagonists & inhibitors
• Flavanones/isolation & purification
• Flavanones/pharmacology
• Gene Expression Regulation, Neoplastic
• Humans
• Imidazoles/pharmacology
• Matrix Metalloproteinase 2/genetics
• Matrix Metalloproteinase 2/metabolism
• Matrix Metalloproteinase 9/genetics
• Matrix Metalloproteinase 9/metabolism
• Microglia/drug effects
• Microglia/metabolism
• Microglia/pathology
• Plant Extracts/chemistry
• Protein Kinase Inhibitors/pharmacology
• Pyridines/pharmacology
• Scutellaria baicalensis/chemistry
• Signal Transduction
• Tissue Inhibitor of Metalloproteinase-1/genetics
• Tissue Inhibitor of Metalloproteinase-1/metabolism
• Tissue Inhibitor of Metalloproteinase-2/genetics
• Tissue Inhibitor of Metalloproteinase-2/metabolism
• p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors
• p38 Mitogen-Activated Protein Kinases/genetics
• p38 Mitogen-Activated Protein Kinases/metabolism