Regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib / 中国药房

OBJECTIVE To investigate the regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib. METHODS Using human liver cancer cell Huh7 as subject， the lenvatinib-resist cell model （Huh7-LR） was generated by the low-dose gradient method combined with long-term administration. The sensitivity of parental cell Huh7 and drug-resistant cell Huh7-LR to lenvatinib was detected by using CCK-8 assay and flow cytometry. Western blot assay and GFP-mCherry-LC3 plasmid transfection were performed to detect the expression levels of autophagic protein Beclin-1， autophagic adapter protein sequestosome 1 （p62）， microtubule-associated protein 1 light chain 3 （LC3） and autophagic level. Furthermore， an autophagy activation model was constructed by cell starvation， the protein expression of p62 and autophagy level were detected by using Western blot assay and GFP-mCherry-LC3 plasmid transfection， and the effect of autophagy activation on the sensitivity of Huh7-LR cells to lenvatinib was detected by flow cytometry. RESULTS Compared with parental cells， the drug resistance index of Huh7-LR cells was 6.2； protein expression of p62 was increased significantly， while apoptotic rate， protein expression of Beclin-1 and LC3Ⅱ/ LC3Ⅰ ratio were all reduced significantly （P＜0.05 or P＜0.01）； the level of autophagy was decreased to some extent. Autophagy activation could significantly increase the protein expression of p62 in Huh7-LR cells （P＜0.05） and autophagy level， and significantly increase its apoptotic rate （P＜0.05）. CONCLUSIONS Autophagy is involved in lenvatinib resistance， and activating autophagy can reverse the resistance of liver cancer cells to lenvatinib to some extent.

Study on the mechanism of curcumin in the treatment of periodontitis through network pharmacology and mole-cular docking / 华西口腔医学杂志

OBJECTIVES@#This study aims to explore the therapeutic targets of curcumin in periodontitis through network pharmacology and molecular docking technology.@*METHODS@#Targets of curcumin and periodontitis were predicted by different databases, and the protein-protein interaction (PPI) network constructed by String revealed the interaction between curcumin and periodontitis. The key target genes were screened for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was performed to analyze the binding potential of curcumin to periodontitis.@*RESULTS@#A total of 672 periodontitis-related disease targets and 107 curcumin-acting targets were obtained from the databases, and 20 key targets were screened. The GO and KEGG analyses of the 20 targets showed that curcumin might play a therapeutic role through the hypoxia-inducible factor (HIF)-1 and parathyroid hormone (PTH) signaling pathways. Molecular docking analysis showed that curcumin had good binding potential with multiple targets.@*CONCLUSIONS@#The potential key targets and molecular mechanisms of curcumin in treating periodontitis provide a theoretical basis for new drug development and clinical applications.

Temporal expression of triggering receptors expressed by myeloid cells-1 during the development of experimental periodontitis in rat / 中华口腔医学杂志

Objective@#To illuminate the temporal expression of the triggering receptor expressed on myeloid cells-1 (TREM-1) in the experimental periodontitis in rat and to investigate the function of TREM-1 in the pathogenesis of experimental periodontitis in rat.@*Methods@#The experimental periodontitis model was established in the maxillary first molar by means of 'wire ligation + vaccination periodontal pathogen Porphyromanus gingivalis (Pg) + high-sugar diet' in Sprague-Dawley (SD) rats. The experimental animals were divided into six groups: the control group and each of the time points of establishing the models for one week and two to five weeks. There were six rats for each of the six groups. The bone loss of the palatal site was calculated to estimate whether the periodontitis model was successfully established. The expression of TREM-1, proinflammatory cytokines: tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6, anti-inflammatory cytokines: IL-4, IL-10 and transforming growth factor-β (TGF-β) were examined by using quantitative real-time PCR. The expression level of TREM-1 protein was analyzed by the method of immunohistochemistry.@*Results@#The average bone loss area of the palatal site was (0.17±0.04) mm2 in the group of three weeks and was statistically significant (P<0.05) compared to the control group [(0.10±0.01) mm2]. The experimental periodontitis model was successfully established in the group of three weeks. The expression of TREM-1 increased significantly in the inflamed periodontal tissues and reached to its maximum expression in the three weeks group accounting for 159.50±38.26 in protein expression and 4.35±0.60 in mRNA expression, respectively. TREM-1 expression difference between the three weeks group and control group was statistically significant (P<0.01). The expression of IL-6 by gingival tissues was correlated with the mRNA level of TREM-1 (r=0.813 P=0.049).@*Conclusions@#TREM-1, as a proinflammatory receptor, could facilitate the periodontal inflammatory response. The possible way of TREM-1 to promote inflammation may be through controling the expression of IL-6.

The research progress in gingival invagination / 中华口腔医学杂志

Gingival invagination is a type of gingival cleft that occurs during orthodontic space closure in some of the orthodontic patients who received tooth extraction. Clinical manifestations may be fine folds in attached gingiva surface, or deep cleft that penetrates the interdental papilla from the buccal to the lingual alveolar process. Gingival invagination can affect the health of local periodontal tissues, the effect and stability of orthodontic treatment. This article reviews the research progress of gingival invagination studies, including the definition, manifestations, causes, influencing factors and effects.

Interpretation of consensuses on treatment of female patients with periodontal disease / 中华口腔医学杂志

Periodontal tissue is the target tissue of sex hormone, physiological change of sex hormones affects the response of periodontal tissue to bacterial plague. The treatment of periodontal disease of female patients in special periods such as adolescence, menstruation, prepregnancy, pregnancy, puerperium, and menopause should be chosen carefully and correctly. This article attempts to expound these issues.

Effects of Porphyromnonas gingivalis lipopolysaccharide on the expression of RANTES and fractalkine in human urnbilical vein endothelial cells / 华西口腔医学杂志

<p><b>OBJECTIVE</b>A study was conducted to investigate the effects of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) on the expression of regulated upon activation normal T-cell expressed and secreted (RANTES) and fractalkine in human umbilical vein endothelial cells (HUVECs).</p><p><b>METHODS</b>HUVECs were incubated with different concentrations of Pg-LPS (200, 500, and 1000 ng x mL(-1)) for 1, 6, 12, and 24 h, respectively. Then real time quantitative polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent method (ELISA) were adopted to detect the protein levels and mRNA levels of RANTES and fractalkine.</p><p><b>RESULTS</b>The RANTES protein levels and mRNA levels, as well as fractalkine mRNA levels, were significantly higher in all experimental groups of 1, 6, and 12 h than in the control group (P<0.05), except the expression of RANTES mRNA in 200 ng x mL(-1) group of 12 h and RANTES protein in 200 ng x mL(-1) group of 1 h. The expression levels of RANTES mRNA and fractalkine mRNA were highest in 1000 ng x mL(-1) group of 6 h and were 4.88- and 6.20-fold higher, respectively, than those in the control group. The expression levels of RANTES protein, mRNA, and fractalkine mRNA decreased 6 h after stimulation, and were significantly higher than those in the control group (P<0.05) in the RANTES and fractalkine in HUVEC, and such expression is important in the development of atherosclerosis 500 ng x mL(-1) group of 24 h. There was a significant difference between the expression of fractalkine mRNA in 1000 ng x mL(-1) group of 6 and 12 h than in the control group (P<0.05).</p><p><b>CONCLUSION</b>Pg-LPS infection might up-regulate the expression of RANTES and fractalkine in HUVEC, and such expression is important in the development of atherosclerosis.</p>

Effect of glutaredoxin on oxidative stress of umbilical vein endothelial cell exposed to Porphyromonas gingivalis lipo- polysaccharide / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study measures the glutaredoxin (Grx) gene and protein expression in umbilical vein endothelial cells upon exposure to Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS). The involvement of the Akt-signaling pathway is also determined.</p><p><b>METHODS</b>EA-hy926 cells were pretreated with 1,000 ng · mL⁻¹ P. gingivalis LPS for 4, 12, 18, and 24 h, and then real-time reverse transcription polymerase chain reaction was employed to detect Grx1 expression. The effect of Grx on Akt activity was investigated using Western blot for the control, LPS (1,000 ng · mL⁻¹ LPS), and carmus- tine (BCNU) groups (1,000 ng · mL⁻¹ LPS, and the EA-hy926 cells were pretreated with 25 μmol · ml⁻¹ BCNU for 30 min).</p><p><b>RESULTS</b>Gene expression of Grx1 significantly increased in LPS group compared with that in the control group. The Grx1 expression reached the peak level in 12 h, and the variation between the expression in 4 and 12 h was significant (P < 0.05). After 12 h, the protein levels of Grx and phosphorylated-Akt (p-Akt) significantly increased in the LPS group (P < 0.05), whereas the BCNU group showed a considerable decrease in both Grx and p-Akt expression levels (P < 0.05). Moreover, a slight difference was observed in the total Akt protein levels in the three groups (P > 0.05).</p><p><b>CONCLUSION</b>Grx expression increased upon exposure of EA-hy926 cells to the LPS. Akt activity could be inhibited by BCNU (a Grx inhibitor), which indicated that Akt might act as a downstream regulator of Grx.</p>

Research progress on the relationship between Porphyromonas gingivalis and oral squamous cell carcinoma / 华西口腔医学杂志

Substantial evidence supports the relationship between chronic inflammation and cancer development. Numerous studies suggest that chronic inflammatory disease, such as periodontitis, contributes to head and neck squamous cell carcinoma development. Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the oral and maxillofacial regions. Porphyromonas gingivalis, one of the most important pathogens in association with periodontal disease, might have a potential correlation with OSCC. Along with the development of molecular biological techniques, the association between Porphyromonas gingivalis and OSCC has been greatly emphasized in recent years. This review summarizes the association between these variables and the potential mechanisms involved in such relationship.

Implant mobility,SBI and PIS changes in patients with chronic periodontitis after implant treatment / 重庆医学

Objective To explore the short‐term effect of chronic periodontitis patients after implant treatment .Methods Selected 60 cases of tooth loss in chronic periodontitis patients as research group ,a total of 75 implants were placed ,and 50 cases of periodontal healthy teeth missing patients as control group ,a total of 67 implants were placed .Compared two groups of modification sulcus bleeding index(mBII) ,papilla index score(PIS) ,modification plaque index(mPLI) and probing depth(PD) 6 months after op‐eration ,and detected implant sulcular fluid IL‐2 ,IL‐8 content in two groups before and after operation .Results Research group 75 implants had 2 off on their own ,implant loosening degrees 0 ,implant survival rate was 97 .3% ;the control group had no implant failure ,implant loosening of implant survival rate was 100% ,two groups of implant survival rate was no significant difference(χ2 =2 .737 ,P= 0 .098) .The mSBI ,PIS ,mPLI ,PD in research group and control group had no statistically significant(P > 0 .05) .Re‐search group sulcular fluid IL‐2 ,IL‐8 content was significantly higher than those in control group before and after the operation (P< 0 .05) .Conclusion The short‐term effect of implant treatment in chronic periodontitis patients is satisfactory ,without increas‐ing the risk of peri‐implantitis ,and worth of clinical promotion .

The effects of Porphyromonas gingivalis infection on mononuclear cell adhesion to vascular endothelial cells / 实用口腔医学杂志

Objective:To elucidate the effects of Pg in modulation of monocyte adhesion to human umbilical vein endothelial cells (HUVECs).Methods:The model of infection of HUVECs by Pg was established in vitro.HUVECs were infected with Pg381 and Pg33277 and then incubated with THP-1 monocytes respectively.The amount of THP-1 adhesion to HUVECs was tested by rose Ben-gal staining assay.Results:Pg381-infected HUVECs demonstrated significantly increased adhesion of THP-1 cells compared to those infected with Pg33277(0.210 ±0.025 vs 0.078 ±0.024,P0.05).Conclusion:The infection of Pg381 can increased the adhesion of monocytes to HUVECs.

Periodontal therapy for rheumatoid arthritis: a systematic review / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To assess the effect and safety of periodontal therapy in relieving the symptoms and clinical signs of rheumatoid arthritis (RA).</p><p><b>METHODS</b>The electronic search was conducted in Medline (OVID, 1950-2010 Sep), EMBASE (1984-2010 Sep), CENTRAL (2010, Issue 3), CBM (1978-2010 Sep) and the Chinese journals on stomatology were hand-searched. Clinical randomized controlled trials as well as clinical controlled trials were selected regarding the targeted issue. Two investigators evaluated the reporting quality and risk of bias of those included trials in accordance with CONSORT statement and Cochrane risk of bias assessment tools, and collected data of included studies in duplicate. Revman 5.0.23 was applied for Meta-analysis.</p><p><b>RESULTS</b>Four trials met the inclusion criteria and a total of 150 patients were enrolled in the trials, one had low risk of bias and others had moderate risk of bias. Meta-analysis showed that pure periodontal therapy could not decrease disease activity score in 28 joints (DAS28) (P=0.06), and there was no statistically significant difference between periodontal therapy with anti-tumor necrosis factor-alpha (TNF-alpha) medication and pure anti-TNF-alpha medication (P=0.24). But the subgroup analysis showed that a significantly decreased DAS28 was achieved by periodontal therapy (P=0.03), and the interventions provided a remarkable effect on alleviating clinical signs and erythrocyte sedimentation rate of RA (P<0.05). Results of the symptoms relief differed from the studies. No adverse events were reported.</p><p><b>CONCLUSION</b>The evidence available currently indicates that periodontal therapy may play a positive role in remitting the clinical signs and periodontal status of RA except the relief of the symptoms.</p>

The effect of pulsed Nd:YAG laser used as an adjunct to subgingival scaling and root planning / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study was to observe and compare the microbiological effects of laser therapy combined with ultrasonic subgingival scaling and root planning (SRP) versus SRP alone.</p><p><b>METHODS</b>26 contra lateral teeth were randomly assigned to the test group (laser + SRP) or the control group (SRP alone). Subgingival microbial samples were collected, cultured and analyzed at baseline, then repeated immediately after laser treatment at week 1, week 2 and week 4.</p><p><b>RESULTS</b>Although both groups had significant increase in G+/G- ratio (P < 0.01), the changes of G+ and G- were more obvious in the test group till week 1(P < 0.05). The total CFU of test group diminished significantly just after laser irradiation (P < 0.05). That revealed the laser therapy followed by SRP appeared to have a stronger effect on converting the subgingival micro-ecosystem to healthy status.</p><p><b>CONCLUSION</b>Laser appeared to have a stronger bactericidal action in vivo. especially on the dark-pigmented G- rods associated with periodontal disease.</p>

Expression of MMP-1 and MMP-8 in periodontal tissues in rats with periodontitis / 实用口腔医学杂志

Objective:To investigate the expression of MMP-1 and MMP-8 in periodontal tissues in rats with periodontitis at different stages of inflammation with varied severity. Methods:Periodontitis was induced by silk ligature. P.gingivalis(Pg) or Pg with F.nu were used to induce the varied severity of periodontitis in 40 rats. 14 and 28 days after periodontitis induction the animals were sacrificed, periodontal tissues were immunohistochemically stained by antibody of MMP-1 and MMP-8 respectively. Results:MMP-1 and MMP-8 were both strongly positive in gingival epithelia cells and fibroblasts in periodontal ligament in rats with periodontitis.Higher expression of MMP-1 and MMP-8 was observed at 14 d than at 28 d(P0.05). Conclusion:The expression of MMP-1 and MMP-8 varies in different stage of periodontitis. MMP-1 and MMP-8 may play an important role in development of periodontitis.

Assessment of the microbiologic and clinical effects of ultrasonic scaling combining with simultaneous antimicrobial agent irrigation / 实用口腔医学杂志

Objective:To assess the clinical and microbiologic effects of ultrasonic scaling with simultanous irrigation with chlorhexidine(CHX), conventional ultrasonic scaling or subgingival irrigation. Methods: 20 teeth in 7 patients with periodontitis were equally divided into test and control group. Patients in the test group were treated by irrigation with CHX during ultrasonic scaling(Master400),those in the control with irrigating after scaling(MiNi ). Clinical assessments of bleeding on probing (BOP),probing depth (PD) were made just before and 7 and 14 days after treatment. The subgingival microbiologic examination was performed before and 0,7 and 14 days after treatment. Result: Significant reductions in PD and BOP were observed in both groups 7 and 14 days after treatment(P