Salvage neck surgery in recurrent nodal NPC: Do all patients require a comprehensive neck dissection in the modern MRI era?

OBJECTIVE: The standard treatment for regional failure in nasopharyngeal carcinoma (NPC) is the radical neck dissection (RND). Our study sought to determine if magnetic resonance imaging (MRI) may accurately predict nodal involvement to allow selected levels of neck dissection to be preserved. STUDY DESIGN AND SETTING: We analysed retrospectively all NPC patients in our centre undergoing neck dissections as salvage therapy for nodal recurrence. Nodal involvement based on the preoperative MRI was assessed and compared with postoperative histopathology. METHODS: This is a retrospective study conducted on patients in our centre with recurrent NPC from February 2002 to February 2017. Patients were identified from the database of the otolaryngology oncology division at our institution. Of these, 28 patients met all our inclusion and exclusion criteria. We calculated sensitivity and specificity as well as average number of nodes per patient. RESULTS: In our study, we calculated the false negative and false positive rates of preoperative MRI neck by levels. Overall sensitivity of MRI picking up disease by level was 76% and specificity was 86%. CONCLUSION: Based on our study, we will be missing a total of 10 (7.1%) diseased neck levels in eight (28.5%) patients. MRI alone, therefore, does not provide enough information to allow safe selective preservation of neck levels in surgical salvage of neck recurrences in NPC.

Knockdown of miR-125b-5p inhibits the proliferation and invasion of gastric carcinoma cells by targeting RYBP.

Gastric carcinoma, one of the most aggressive and lethal human malignancies, is associated with poor prognosis despite progress in therapeutic strategies. This study examined the potential function and mechanism of action of microRNA-125b-5p (miR-125b-5p) in the pathogenesis of gastric carcinoma. We recognized that miR-125b-5p was elevated in gastric carcinoma, and its decreased expression was associated with a better prognosis. Loss-of-function assays showed that miR-125b-5p suppression inhibited the proliferative and invasive abilities of gastric cancer cells. Furthermore, RING1 and YY1-binding protein (RYBP) was found to be target gene for miR-125b-5p action; miR-125b-5p negatively regulates RYBP expression. According to the results of rescue experiments, RYBP downregulation partially counteracted the miR-125b-5p silence-mediated inhibitory function in gastric cancer progression. Collectively, these data elucidated the molecular mechanisms of the miR-125b-5p/RYBP axis in gastric cancer invasion and growth.

Self-expanding metal stent insertion by colorectal surgeons using a two-person approach colonoscopy without fluoroscopic monitoring in the management of acute colorectal obstruction: a 14-year experience.

BACKGROUND: Placement of a self-expanding metal stent (SEMS) in patients presenting with an acute colorectal obstruction (ACO) may obviate emergency surgery (ES), potentially effectively palliating incurable tumors, acting as a bridge to surgery (BTS) in patients with operable or potentially operable tumors and achieving effective decompression of other ACO. We present our experience with SEMS insertion by colorectal surgeons without fluoroscopic monitoring for ACO especially for acute malignant colorectal obstruction (AMCO) for nearly a 14-year period (2007-2020). AIM: To explore the safety and effectiveness of SEMS insertion in the management of ACO by colorectal surgeons using a two-person approach colonoscopy without fluoroscopic monitoring. METHODS: We reviewed the medical records of patients retrospectively to identify all patients presenting to our unit with ACO especially with AMCO who had stenting carried out to achieve colonic decompression. All 434 procedures were performed by colorectal surgeons using a two-person approach colonoscopy without fluoroscopic monitoring. RESULTS: The overall technique success rate and clinic success rate by SEMS insertion were 428/434 (98.6%) and 412/434 (94.9%). The overall incidence of complications by SEMS insertion was 19/434 (4.4%). The complications included clinical perforation (6/434, 1.4%); stent migration (2/434, 0.5%), 1 of which re-stent; stent detachment (fell off) (3/434, 0.7%), none of them with re-stent; stool impaction (6/434, 1.4%), 1 of which re-stent; and abdominal or anal pain (2/434, 0.5%). There was no hemorrhage in any of the 434 patients. CONCLUSIONS: SEMS insertion is a relatively safe and effective technique for colonic decompression in dealing with ACO as either a BTS or as a palliative measure. It is also a solution to other causes of ACO such as recurrent tumor, benign diseases, or extra-luminal compression. Therefore, ES was largely avoided.

Earthworm activity and its coupling to soil hydrology: A deterministic analysis.

Considering in situ observations, chaos theory was taken as a basis to study the activity of anecic earthworms based on cast production from September 2016 to January 2018 in the Dong Cao watershed (Vietnam). To study this activity, the global modeling technique was used to obtain deterministic models of ordinary differential equations directly from observational time series. The obtained models show that the behavior of earthworms is chaotic; it is coupled to the dynamics of soil water content in a complex (integrative) way and can be interpreted as an habituation/sensitization process. However, this coupling is insufficient to explain the desynchronization of the cast production variations observed at different study sites. The retroaction of earthworm activity on soil is required to explain the spatiotemporal discrepancies.

Quinone-amine polymers as metal-free and reductant-free catalysts for hydroxylation of benzene to phenol with molecular oxygen.

Quinone-amine polymers were employed as metal-free and reductant-free catalysts for the hydroxylation of benzene to phenol with molecular oxygen, yielding phenol as high as the transition metal catalyst.

[Diagnostic value of endobronchial ultrasonography with guide-sheath combined with virtual bronchoscopy navigation in peripheral lung cancer].

Objective: To explore the diagnostic value and safety of endobronchial ultrasonography with guide-sheath (EBUS-GS) combined with virtual bronchoscopy navigation (VBN) in peripheral lung cancer. Methods: Between Dec. 2015 to Dec. 2016, patients with pulmonary solitary nodule suspected of early lung cancer on computed tomography (CT) in Department of Respiratory, Tangdu Hospital, Fourth Military Medical University were enrolled for this study. The patients underwent EBUS-GS transbronchoscopic lung biopsy (TBLB) with or without VBN. The visibility rate, diagnostic yield, influencing factors, the operation time and complications were evaluated in the 2 groups. The data were compared using independent sample t test or chi-squared test. Results: A total of 134 patients were enrolled and completed this study. Among them 74 were males and 60 were females. There were 64 cases in the group of EBUS-GS with VBN (VBNA), and 70 in the group without VBN (NVBNA). The visibility rate and diagnosis rate of VBNA group were 87.5% (56/64) and 78.1% (50/64), respectively. The mean time of operation and confirming the target lesions were (25±5), (5.8±1.3) min, respectively. The visibility rate and diagnosis rate of NVBNA group were 81.4%(57/70) and 75.7%(53/70), respectively. The mean time of operation and confirming the target lesions were (27±6), (9.8±1.5)min .There was no significant difference in the visibility rate and diagnosis rate between the 2 groups (χ(2)=0.933, P=0.334; χ(2)=0.109, P=0.838). There was no significant difference in the mean operation time between the 2 groups(t=0.633, P=0.524). But the time of confirming the target lesions between the 2 groups was statistically different (t=17.41, P<0.01). EBUS-GS-TBLB was well tolerated. No severe complications such as pneumothorax or chest pain were observed. There were 3 patients in the VBNA group and 7 patients in the NVBNA group experiencing a small amount of biopsy site bleeding. The incidence of complications did not differ between the 2 groups(χ(2)=1.366, P=0.330). Conclusions: VBN could not improve the diagnostic yield of EBUS-GS. However, it could shorten the time needed to confirm the target lesions and did not increase the incidence of EBUS-GS complications, indicating that EBUS-GS with VBN was a safe and effective method.

Pharyngeal airway changes following maxillary expansion or protraction: A meta-analysis.

The aim of this meta-analysis was to investigate the changes in airway dimensions after rapid maxillary expansion (RME) and facemask (FM) protraction. Using PubMed, Medline, ScienceDirect and Web of Science, only controlled clinical trials, published up to November 2016, with RME and/or FM as keywords that had ≥6 months follow-up period were included in this meta-analysis. The changes in pharyngeal airway dimension in both two-dimensional and three-dimensional images were included in the analysis. Nine studies met the criteria. There are statically significant changes in upper airway and nasal passage airway in the intervention groups as compared to the control groups, assessed in two-dimensional and three-dimensional images. However , in the lower airway and the airway below the palatal plane, no statistically significant changes are seen in 2D and 3D images. RME/FM treatments might increase the upper airway space in children and young adolescents. However, more RCTs and long-term cohort studies are needed to further clarify the effects on pharyngeal airway changes.

Capacity-oriented approaches to developing childhood obesity interventions: a systematic review.

Capacity-oriented approaches to health interventions seek to empower the target population or community to manage the health issue themselves using resources they can control. Positive deviance, resilience and asset-based approaches are three such methods of developing and implementing health interventions. This study aimed to review the efficacy of interventions explicitly applying these methods in addressing childhood obesity using adiposity as the primary outcome, measured by standardized body mass index. The search strategy was developed and implemented across four electronic databases. Of the 181 records identified and screened, 11 studies were identified as using a capacity-oriented approach overall. Asset-based approaches (n = 8 studies) consisted of 47 880 participants, positive deviance (n = 2 studies) consisted of 781 participants, and resilience-based interventions (n = 1 study) consisted of 35 participants. The asset-based approaches were mixed, with three of the eight studies showing a significant reduction in adiposity, while the other five did not find a difference. The positive deviance and resilience-based studies showed signs of efficacy in reducing adiposity. There was significant design heterogeneity across studies, and varied interpretations and definitions of the approaches were used. Further work should attempt to achieve some consensus on the use of these approaches to facilitate comparison and advance the science of capacity-oriented interventions for childhood obesity.

Effect of high glucose, Porphyromonas gingivalis lipopolysaccharide and advanced glycation end-products on production of interleukin-6/-8 by gingival fibroblasts.

BACKGROUND AND OBJECTIVE: It is known that chronic periodontal infection can magnify the cytokine responses in patients with diabetes. Hyperglycemia increases the proinflammatory status, including the levels of advanced glycation end-products (AGEs), in patients with periodontitis. However, whether AGEs have additional effects on the production of those proinflammatory cytokines in diabetic patients with periodontitis is still unknown. To examine in vitro the effect of hyperglycemia and AGEs on the amounts of interleukin (IL)-6 and IL-8 produced in periodontally infected gingiva, human gingival fibroblasts (HGFs) were stimulated with glucose, AGE-modified bovine serum albumin (AGE-BSA) and Porphyromonas gingivalis LPS in the present study. MATERIAL AND METHODS: Primary culture of HGFs was incubated with various concentrations of AGE-BSA (0, 50, 100 and 200 µg/mL) and LPS (0, 10, 100 or 1000 ng/mL) at two different glucose concentrations - normal glucose (5 mm) and high glucose (25 mm). The amounts of IL-6 and IL-8 produced by HGFs were evaluated using ELISA. Expression of the AGE receptor on HGFs was determined by flow cytometry. RESULTS: High glucose stimulated a significant increase in the production of IL-6 and IL-8 by HGFs compared with normal glucose. This enhanced production of IL-6 and IL-8 could also be observed in the presence of LPS and/or AGE-BSA. When both LPS and AGE-BSA were present, especially at high concentrations (≥ 500 µg/mL of LPS and ≥ 25 µg/mL of AGE-BSA), a synergistic effect on IL-8 production was found in the high-glucose condition. CONCLUSIONS: A synergistic effect of the production of IL-8 could be induced in HGFs with the combination of high glucose, LPS and AGEs.

What determines the interfacial configuration of Nb/Al2O3 and Nb/MgO interface.

Nb films are deposited on single crystal Al2O3 (110) and MgO(111) substrates by e-beam evaporation technique. Structure of Nb films and orientation relationships (ORs) of Nb/Al2O3 and Nb/MgO interface are studied and compared by the combination of experiments and simulations. The experiments show that the Nb films obtain strong (110) texture, and the Nb film on Al2O3(110) substrate shows a higher crystalline quality than that on MgO(111) substrate. First principle calculations show that both the lattice mismatch and the strength of interface bonding play major roles in determining the crystalline perfection of Nb films and ORs between Nb films and single crystal ceramic substrates. The fundamental mechanisms for forming the interfacial configuration in terms of the lattice mismatch and the strength of interface bonding are discussed.

Fasudil alleviated hypoxia-induced pulmonary hypertension by stabilizing the expression of angiotensin-(1-7) in rats.

OBJECTIVE: The aim of this study was to investigate the mechanism of fasudil alleviating hypoxic pulmonary hypertension (HPH). MATERIALS AND METHODS: A total of 50 Sprague-Dawley rats were randomized into control, model and fasudil intervention groups. Hemodynamic and pulmonary pathomorphology data were collected using Powerlab system and hematoxylin and eosin staining. The protein expression of Ang-(1-7) was detected by immunohistochemical staining and ELISA assay in vivo or in vitro. Western blot was utilized to observe the protein expression of ACE2 and HIF-1α in vitro. RESULTS: Fasudil treatment repressed the elevation of RVSP, RV/(LV+S), attenuated the pulmonary vascular structure remodeling (PVSR) of pulmonary arterioles induced by chronic hypoxia, and stabilized the expression of Ang-(1-7) in vivo and in vitro. In addition, experiments consistently indicated an escalation of ACE2 and a reduction of HIF-1α. CONCLUSIONS: Our results suggest that fasudil can effectively attenuate PVSR and PH. The underlying mechanism may partially up-regulated Ang-(1-7) and ACE2, and lessened HIF-1α.

A Salvia miltiorrhiza ethanol extract ameliorates tissue destruction caused by experimental periodontitis in rats.

BACKGROUND AND OBJECTIVE: Salvia miltiorrhiza Bunge (Labiatae), or Danshen, is a Chinese medicine used for treatment of cardiac diseases by improving blood circulation and inhibiting inflammatory responses. In this study, we aimed to determine whether an ethanol extract of S. miltiorrhiza can ameliorate tissue damage caused by periodontitis. MATERIAL AND METHODS: An ethanolic extract of S. miltiorrhiza roots was prepared, and its major constituents were determined by HPLC analysis, by comparison with known standards for the major bioactive components. The activity of the extract was evaluated in a rat model in which periodontitis was induced by ligation of a silk suture around the neck of molar teeth. The effects of the S. miltiorrhiza extract on periodontitis were assessed by dental radiography, micro-computed tomography and histology. RESULTS: The cemento-enamel junction-bone distances among the four different groups of rats were significantly different: the distance was shorter in groups treated with ligation + S. miltiorrhiza extract than in the group treated with ligation only, but was longer than in the nonligated group, regardless of the radiographic methods used. Histology and histometry also indicated a similar trend of less gingival inflammation and alveolar bone destruction in the histological sections from the S. miltiorrhiza extract groups than in those from the ligation group. CONCLUSION: Because the S. miltiorrhiza extract reduced tissue damage and bone loss caused by ligation-induced periodontitis in rats, we suggest that the S. miltiorrhiza extract might have an ameliorative effect on periodontal tissue destruction during the process of periodontitis.

Root coverage by coronally advanced flap with connective tissue graft and/or enamel matrix derivative: a meta-analysis.

BACKGROUND AND OBJECTIVE: Previous systematic reviews have reported that the use of a coronally advanced flap (CAF) combined with a connective tissue graft (CTG) or enamel matrix derivative (EMD) is more likely to achieve complete root coverage (CRC) than other modalities. However, the details of periodontal parameters and comparisons among a variety of combinations of CAF with CTG and/or EMD are left to be investigated. This study aimed to analyze the differences in periodontal parameters between these treatment modalities. MATERIAL AND METHODS: A literature search was performed using the Cochrane library and MEDLINE (PubMed) for studies focused on the treatment of gingival recession (Miller Class I, II and III) with CAF alone or combined with CTG, EMD or both up to December 2011. Randomized controlled clinical trials with a follow-up duration ≥ 6 mo were included. The outcome analysis included changes in periodontal probing depth (PPD), clinical attachment level, recession depth (RED) and keratinized tissue width (KTW). RESULTS: Thirteen randomized controlled clinical trials, including 529 Miller Class I-III defects from 321 patients were included. For an increase in KTW, CAF + CTG significantly improved more than CAF alone. CAF + EMD also gained more KTW than CAF alone. EMD reduced PPD, however, a significant difference was not found. Furthermore, the effects on changes of RED and clinical attachment level were not identified in the study. CONCLUSION: When combined with CAF, CTG contributed more in the increase of KTW, while EMD seemed helpful for wound healing by its potential in PPD reduction. However, further research is needed to clarify the effects on changes in RED and clinical attachment level.

The effects of diallyl sulfide upon Porphyromonas gingivalis lipopolysaccharide stimulated proinflammatory cytokine expressions and nuclear factor-kappa B activation in human gingival fibroblasts.

BACKGROUND AND OBJECTIVE: Diallyl sulfide (DAS), a flavor compound from garlic, has varied potential therapeutic activities. Periodontitis is a disease that develops because of host-mediated inflammation to periodontal pathogens. In this study, the effects of DAS on the common proinflammatory cytokines and nuclear factor-kappa B (NF-κB) in human gingival fibroblasts (HGFs) being stimulated with lipopolysaccharide from Porphyromonas gingivalis, a potent periodontal pathogen, were evaluated. MATERIAL AND METHODS: Cytotoxicities of DAS and lipopolysaccharide on HGFs were measured with MTS assay. The mRNA and protein expressions of proinflammatory cytokines, including interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α, from the HGFs treated with lipopolysaccharide with and without DAS were examined with reverse transcription-polymerase chain reaction and immunocytochemistry, respectively. In addition, the activation and nuclear translocation of NF-κB with and without DAS were compared. RESULTS: DAS and lipopolysaccharide treatments within 3 mm and 10 µg/mL, respectively, did not affect the survival rate of HGFs. Lipopolysaccharide (1 µg/mL) significantly increased the mRNA expressions of IL-1ß, IL-6 and TNF-α; however, DAS (1 mm) inhibited these expressions. The protein expressions of TNF-α, IL-1ß, as well as the NF-κB nuclear translocation were increased after lipopolysaccharide treatment, but decreased when there was a DAS pretreatment. CONCLUSION: DAS diminished P. gingivalis lipopolysaccharide-stimulated cytokine expression and NF-κB activation in HGFs; we therefore suggest DAS may be beneficial on periodontal inflammation.

Cyclosporine A up-regulates Sonic hedgehog in gingiva: role of the up-regulation on gingival cell proliferation.

BACKGROUND AND OBJECTIVE: Sonic hedgehog protein (SHH) is a mitogen that stimulates cell proliferation. Cyclosporine A enhances the proliferation of gingival cells; however, the relationships of SHH to cyclosporine A or to cyclosporine A-enhanced gingival cell proliferation have not been described. MATERIAL AND METHODS: Here, we investigated SHH expression in gingiva in vitro and in vivo after cyclosporine A treatment and tested the effect of SHH inhibition on cyclosporine A-enhanced gingival fibroblast proliferation in vitro. RESULTS: In human gingival fibroblasts, cyclosporine A treatment increased the expression of SHH transcripts and SHH protein, and stimulated cell proliferation; the addition of cyclopamine, an SHH signaling inhibitor, suppressed cyclosporine A-enhanced cell proliferation. Up-regulated expression of SHH and up-regulation of proliferating cell nuclear antigen transcripts and protein were observed in the edentulous gingiva of cyclosporine A-treated rats. CONCLUSION: Cyclosporine A up-regulates gingival SHH expression in vitro and in vivo, and the inhibition of the SHH pathway counteracts the stimulatory effect of cyclosporine A on gingival fibroblast proliferation. Therefore, we suggest that SHH mediates a novel molecular mechanism for cyclosporine A-induced gingival complications.

Cyclosporine-A inhibits MMP-2 and -9 activities in the presence of Porphyromonas gingivalis lipopolysaccharide: an experiment in human gingival fibroblast and U937 macrophage co-culture.

BACKGROUND AND OBJECTIVE: Studies have shown that bacterial plaque and the associated gingival inflammation increase the severity of gingival overgrowth induced by cyclosporine-A (CsA). This in vitro study aimed to evaluate the effect of CsA on the activities of MMPs from the co-culture of human gingival fibroblasts and U937 macrophages in the presence or absence of Porphyromonas gingivalis lipopolysaccharide (LPS). MATERIAL AND METHODS: Activities of pro-MMP-2, MMP-2 and pro-MMP-9 in the supernatants of independent cultures and co-cultures were examined by zymography. RT-PCR was selected to evaluate the expression of mRNA for membrane type-1 (MT1) MMP in the co-cultures. RESULTS: Activities of MMPs in the co-cultures were significantly greater when compared with any of the independent cultures. Lipopolysaccharide significantly increased the MMP activities in a dose-dependent manner in the co-cultures, whereas CsA inhibited these activities. In the presence of both CsA and LPS, the MMP activities inhibited by CsA could still be observed in the co-cultures. In the individual cultures, in contrast, the CsA-inhibited MMP activities, in the presence of LPS, were minimally detected. The mRNA expression of MT1-MMP was significantly enhanced after LPS treatment; however, this enhancement was inhibited by CsA. CONCLUSION: This study demonstrated that, in co-cultures of human gingival fibroblasts and U937 macrophages, CsA could inhibit MMP activities in the presence of P. gingivalis LPS. It might be part of the underlying reason for the persistent overgrowth of gingiva seen when bacterial plaque and local inflammation are present during CsA therapy.

Suppression of lung cancer metastasis-related protein 1 (LCMR1) inhibits the growth of colorectal cancer cells.

Lung cancer metastasis-related protein 1 (LCMR1) is a critical subunit of the mediator complex, and plays an important role in the elaborate regulation of gene transcription. However, the functional role of LCMR1 in colorectal carcinoma (CRC) has not been clarified. In this study, LCMR1 expression in CRC specimens was quantified by using the quantitative reverse transcription polymerase chain reaction method. The effect of downregulation of LCMR1 by lentivirus-mediated small hairpin RNA (shRNA) on CRC cell proliferation and tumorigenesis was explored. There was a higher expression of LCMR1 in CRC tissue in comparison with adjacent normal colon tissue (P < 0.05). LCMR1 gene was effectively knocked down in human CRC RKO and DLD-1 cells that infected with lentivirus delivering shRNA against LCMR1, which resulted in inhibition of cell proliferation and augmentation of G0/G1 phase proportion. Moreover, the tumorigenicity of RKO cells was also dramatically inhibited after LCMR1 was knocked down. In conclusion, our results suggest that LCMR1 promotes CRC cell growth, and lentivirus-mediated silencing of LCMR1 may contribute to the gene therapy for CRC.

Effect of cyclosporine-A on orthodontic tooth movement in rats.

OBJECTIVE: The objective of this study is to examine the effect of cyclosporine-A (CsA) on the rate of orthodontic tooth movement in rats. SETTING AND SAMPLE POPULATION: This is a randomized controlled trial with a split-mouth design in Sprague-Dawley rats. MATERIAL AND METHODS: Eighteen rats, divided at random in two groups, were fed with 8 mg/kg CsA (experiment) or mineral oil (control) daily after initial healing of bilateral maxillary second molar removal. All rats received orthodontic coil springs (10 cN) secured to the maxillary incisors and first molars at the rights side, while no springs were placed at the left. Distances between first and third molars were measured on days 0, 3, 6, and 12. After sacrificing on day 12, the alveolar ridges of the maxillae were sectioned and blood samples were collected for serum tartrate-resistant acid phosphatase (TRAP)-5b level detection and for histology, respectively. RESULTS: Significantly larger changes in intermolar distances were found after orthodontic force application in the CsA group at days 3 and 12 when compared with the control group. The inter-radicular dental alveolus of CSA-fed rats was osteopenic. Significantly increased TRAP-5b serum level was noted in the CsA group when compared with the control group. CONCLUSIONS: We suggest that CsA enhanced the rate of orthodontic tooth movement. The osteopenia and the increased osteoclastic activity could be the underlying factors.

Nrf-2 regulates cyclosporine-stimulated HO-1 expression in gingiva.

Cyclosporine-A (CsA) stimulates heme oxygenase-1 (HO-1) expression in the gingiva, but the regulation and the role of HO-1 in gingival overgrowth are not well-understood. HO-1 is regulated by several transcription factors, such as nuclear factor-κB (NF-κB) and nuclear factor erythroid-2-related factor 2 (Nrf-2). The aim of this study was to examine the role of Nrf-2 in the regulation of CsA-stimulated HO-1 expression in human gingival fibroblasts. Nrf-2 siRNA (siNrf-2), NF-κB, kinase inhibitors, and sulforaphane (SFN) were used to examine the nuclear translocation of Nrf-2 and expression of HO-1 and transforming growth factor-ß1 (TGF-ß1) in cells. Treatment with siNrf-2, but not with an NF-κB inhibitor, reduced CsA-stimulated HO-1 mRNA expression. ERK inhibition significantly decreased CsA-stimulated Nrf-2 nuclear translocation and HO-1 mRNA expression. Pre-treatment with SFN showed that HO-1 plays a role in attenuating CsA-mediated TGF-ß1 expressions. These findings suggest that CsA-stimulated HO-1 expression is mediated through the activation of ERK, and that Nrf-2 plays a protective role against CsA-induced gingival fibrosis by modulating collagen turnover-related genes.