Sensory Stimuli to Sustainable Social Wellbeing: A Multimodal Approach Based on Warm Scent.

Sensory experiences affect individuals' judgment and behavior through the metaphors that experiences carry. The literature has demonstrated that the perception of warmth activates concepts related to positive meaning and metaphors, such as consideration and gentleness, which increase individuals' tendency to help or relate to others. This study hypothesized that warm olfactory stimuli influence intention toward prosocial behavior by increasing the need for social connectedness (NSC). The first experiment (n = 123) demonstrated that the actual warm scent increased participants' intentions for prosocial behavior and that the effect of the actual warm scent was mediated by NSC. Using Amazon Mechanical Turk (MTurk), a second experiment (n = 995) was conducted the showed that warm scent simulated via visual stimuli (i.e., a multimodal approach) led to prosocial behavior intention as well. The results of the study provide academic and managerial insights into how to improve prosocial behavior intention, which is essential for the sustainable development of societies.

Identification of Speech Characteristics to Distinguish Human Personality of Introversive and Extroversive Male Groups.

According to the similarity-attraction theory, humans respond more positively to people who are similar in personality. This observation also holds true between humans and robots, as shown by recent studies that examined human-robot interactions. Thus, it would be conducive for robots to be able to capture the user personality and adjust the interactional patterns accordingly. The present study is intended to identify significant speech characteristics such as sound and lexical features between the two different personality groups (introverts vs. extroverts), so that a robot can distinguish a user's personality by observing specific speech characteristics. Twenty-four male participants took the Myers-Briggs Type Indicator (MBTI) test for personality screening. The speech data of those participants (identified as 12 introvertive males and 12 extroversive males through the MBTI test) were recorded while they were verbally responding to the eight Walk-in-the-Wood questions. After that, speech, sound, and lexical features were extracted. Averaged reaction time (1.200 s for introversive and 0.762 s for extroversive; p = 0.01) and total reaction time (9.39 s for introversive and 6.10 s for extroversive; p = 0.008) showed significant differences between the two groups. However, averaged pitch frequency, sound power, and lexical features did not show significant differences between the two groups. A binary logistic regression developed to classify two different personalities showed 70.8% of classification accuracy. Significant speech features between introversive and extroversive individuals have been identified, and a personality classification model has been developed. The identified features would be applicable for designing or programming a social robot to promote human-robot interaction by matching the robot's behaviors toward a user's personality estimated.

Synthesis, Structure Revision, and Cytotoxicity of Nocarbenzoxazole G.

The total synthesis of nocarbenzoxazoles F (1) and G (2), originally obtained from the marine-derived halophilic bacterial strain Nocardiopsis lucentensis DSM 44048, was achieved via a simple and versatile route involving microwave-assisted construction of a benzoxazole skeleton, followed by carbon-carbon bond formation with the corresponding aryl bromides. Unfortunately, the 1H and 13C NMR spectra of natural nocarbenzoxazole G did not agree with those of the synthesized compound. In particular, the spectra of the isolated and synthesized compounds showed considerable differences in the signals from the protons and carbons in the aryl group. The revised structure was validated by the total synthesis of the actual nocarbenzoxazole G (8c) molecule, which is a regioisomer of the compound that was reported earlier as nocarbenzoxazole G. The synthesized derivatives showed specific cytotoxicity to the human cervical carcinoma cell line, HeLa, but did not have any remarkable effect on the other cell lines.

Predictors of postoperative eGFR change and resolution of hyperfiltration in obese patients following bariatric surgery.

BACKGROUND: Bariatric surgery (BS) can improve glomerular hyperfiltration (GHPF). Very few studies identified associative factors with glomerular filtration rate and resolution from GHPF after BS. OBJECTIVES: To investigate the predictors of estimated GFR (eGFR) changes and resolution from GHPF after BS. SETTING: University hospital, Republic of Korea. METHODS: We enrolled patients who underwent BS for obesity from January 2008 to December 2014 and had more than a year of follow-up. GHPF was defined as an eGFR above 95th percentile values for age- and sex-matched cohorts extracted from the Korea National Health and Nutrition Examination Survey Database. Patients with baseline eGFR less than 60 mL/min/1.73 m2 were excluded. RESULTS: A total of 138 patients (age interquartile range [IQR] 28-43; 21 men, 117 women) were analyzed. The median follow-up period was 36 months (IQR 25-45 mo). One hundred twenty patients (87%) were defined as having GHPF and 75 (54%) resolved after surgery. Multivariate analysis found that sex, preoperative body mass index (BMI), and age were predictive of postoperative eGFR. In patients with preoperative GHPF, female and lower BMI groups had significantly higher resolution rates (P = .012 for sex, P = .016 for BMI). Younger age was related with early resolution after BS. CONCLUSIONS: Younger patients had a faster eGFR decline after BS. Predictive factors for resolution of GHPF after BS include female sex and lower BMI.

Rigidity of silicone substrates controls cell spreading and stem cell differentiation.

The dependences of spreading and differentiation of stem cells plated on hydrogel and silicone gel substrates on the rigidity and porosity of the substrates have recently been a subject of some controversy. In experiments on human mesenchymal stem cells plated on soft, medium rigidity, and hard silicone gels we show that harder gels are more osteogenic, softer gels are more adipogenic, and cell spreading areas increase with the silicone gel substrate rigidity. The results of our study indicate that substrate rigidity induces some universal cellular responses independently of the porosity or topography of the substrate.

Correlation between Semi-Quantitative (18)F-FDG PET/CT Parameters and Ki-67 Expression in Small Cell Lung Cancer.

PURPOSE: The aim of this study was to evaluate the relationship between semiquantitative parameters on (18)F-FDG PET/CT including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) and the expression level of Ki-67 in small-cell lung cancer (SCLC). METHODS: Ninety-four consecutive patients with SCLC were enrolled in this study. They underwent (18)F-FDG PET/CT for initial evaluation of SCLC, and we measured SUVmax, avgSUVmean, MTVsum, and TLGtotal on (18)F-FDG PET/CT images. The protein expression of Ki-67 was examined by immunohistochemical staining. RESULTS: Significant correlations were found between the MTVsum and Ki-67 labeling index (r = 0.254, p = 0.014) and the TLGtotal and Ki-67 labeling index (r = 0.239, p = 0.020). No correlation was found between the SUVmax and Ki-67 labeling index (r = 0.116, p = 0.264) and the avgSUVmean and Ki-67 labeling index (r = 0.031, p = 0.770). Dividing the Ki-67 expression level into three categories, it was suggested that increasing Ki-67 expression level caused a stepwise increase in the MTVsum and TLGtotal. (p = 0.028 and 0.039, respectively), but not the SUVmax and avgSUVmean (p = 0.526 and 0.729, respectively). CONCLUSION: In conclusion, the volume-based parameters of (18)F-FDG PET/CT correlate with immunohistochemical staining of Ki-67 in SCLC. Measurement of the MTVsum and TLGtotal by (18)F-FDG PET/CT might be a simple, noninvasive, and useful method to determine the proliferative potential of cancer cells.

Concurrent Carotid Inflammation in Acute Coronary Syndrome as Assessed by (18)F-FDG PET/CT: A Possible Mechanistic Link for Ischemic Stroke.

BACKGROUND: Patients with acute coronary syndrome (ACS) are prone to ischemic stroke (IS) especially during the early phase. ACS patients are more likely to have concurrent complex carotid plaques which, when destabilized, may serve as a source of distal embolism. This study investigated whether inflammatory activity in carotid artery was increased in ACS survivors compared to chronic stable angina (CSA) patients. METHODS: We prospectively enrolled 74 patients with ACS or CSA (39 ACS patients versus 35 CSA patients), and fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) was performed within 1 week after diagnosis. Carotid PET signal was quantified as standardized uptake value (SUV) and target-to-background ratio (TBR, carotid SUV/jugular venous SUV). RESULTS: Baseline characteristics were similar between groups. TBRs and SUVs were significantly higher in the carotid arteries of ACS patients than those of CSA patients (P < .001). Systemic inflammatory biomarker correlated significantly with carotid FDG uptake (high-sensitivity C-reactive protein versus average SUV: r = .361, P = .002), and the presence of cardiovascular risk factors was also related to inflammation activity. During follow-up, 3 cerebrovascular events occurred in ACS patients (including 1 early IS in a patient with severe baseline carotid inflammation), whereas none in CSA patients (P = .057). CONCLUSIONS: This study provided in vivo evidence that ACS survivors might experience concurrent carotid arterial inflammation. Our findings supported the role of systemic immune activation contributing to multiarterial instability in symptomatic atherosclerosis as a possible mechanistic link between ACS and IS.

Value of (18)F-FDG PET/CT in the Detection of Ovarian Malignancy.

PURPOSE: Ovarian cancer is a leading cause of gynecologic malignancy. As symptoms of ovarian cancer are nonspecific, only 20 % of ovarian cancers are diagnosed while they are still limited to the ovaries. Thus, early and accurate detection of disease is important for an improved prognosis. For the accurate and effective diagnosis of ovarian malignancy on (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT), we analyzed several parameters, including visual assessment. METHOD: A total of 51 peritoneal lesions in 19 patients who showed ovarian masses with diffuse peritoneal infiltration were enrolled. Twelve patients were confirmed to have ovarian malignancy and seven patients with benign disease by pathologic examination. All patients were examined by (18)F-FDG PET/CT, and an additional 2-h delayed (18)F-FDG PET/CT was also performed for 15 patients with 42 peritoneal lesions. We measured semiquantitative parameters including maximum and mean standardized uptake values (SUVmax, SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on a 1-h initial (18)F-FDG PET/CT image (Parameter1) and on a 2-h delayed image (Parameter2). Additionally, retention indices of each parameter were calculated, and each parameter among the malignant and benign lesions was compared by Mann-Whitney U test. We also assessed the visual characteristics of each peritoneal lesion, including metabolic extent, intensity, shape, heterogeneity, and total visual score. Associations between visual grades and malignancy were analyzed using linear by linear association methods. Moreover, a receiver operating characteristic (ROC) curve was analyzed to compare the effectiveness of significant parameters. RESULT: In a comparison between the malignant and benign groups in the analysis of 51 total peritoneal lesions, SUVmax1, SUVmean1, and TLG1 showed significant differences. Also, in the analysis of 42 peritoneal lesions that underwent an additional 2-h (18)F-FDG PET/CT examination, SUVmax1,2, SUVmean1,2, TLG2, and the RI of TLG showed significant differences between the malignant and benign groups. MTV did not show significant differences in either the analysis of 51 peritoneal lesions or of 42 lesions. Regarding visual assessments, metabolic intensity, shape, heterogeneity, and total visual score showed an association with malignancy. In the ROC analysis, the AUC of the visual score was larger than the AUC of other parameters in both the analyses of 51 peritoneal lesions and of 42 lesions. CONCLUSION: Although further study with a larger patient population is needed, the visual assessment of (18)F-FDG PET/CT imaging has a primary role in the detection of malignancy in ovarian cancer patients with assistance from other semi-quantitative parameters.

CD98hc (SLC3A2) loss protects against ras-driven tumorigenesis by modulating integrin-mediated mechanotransduction.

CD98hc (SLC3A2) is the heavy chain component of the dimeric transmembrane glycoprotein CD98, which comprises the large neutral amino acid transporter LAT1 (SLC7A5) in cells. Overexpression of CD98hc occurs widely in cancer cells and is associated with poor prognosis clinically, but its exact contributions to tumorigenesis are uncertain. In this study, we showed that genetic deficiency of CD98hc protects against Ras-driven skin carcinogenesis. Deleting CD98hc after tumor induction was also sufficient to cause regression of existing tumors. Investigations into the basis for these effects defined two new functions of CD98hc that contribute to epithelial cancer beyond an intrinsic effect of CD98hc on tumor cell proliferation. First, CD98hc increased the stiffness of the tumor microenvironment. Second, CD98hc amplified the capacity of cells to respond to matrix rigidity, an essential factor in tumor development. Mechanistically, CD98hc mediated this stiffness sensing by increasing Rho kinase (ROCK) activity, resulting in increased transcription mediated by YAP/TAZ, a nuclear relay for mechanical signals. Our results suggest that CD98hc contributes to carcinogenesis by amplifying a positive feedback loop, which increases both extracellular matrix stiffness and resulting cellular responses. This work supports a rationale to explore the use of CD98hc inhibitors as cancer therapeutics.

The role of interim 18F-FDG PET/CT in predicting early response to neoadjuvant chemotherapy in breast cancer.

AIM: The aim of this study was to prove the diagnostic value of interim 18F-Fluorodeoxyglucose-positron-emission tomography combined with computed tomography (PET/CT) scan for predicting pathological complete response (pCR) compared to other factors in neoadjuvant chemotherapy. PATIENTS AND METHODS: Twenty-seven patients with breast cancer were included in this retrospective study. They all underwent scheduled neoadjuvant chemotherapy. Patients underwent PET/CT at baseline, mid-point (interim), and preoperatively (after completion of chemotherapy). The metabolic response was calculated as follows: ΔStandardized uptake value (SUV)(%)=(1st SUV(max)-2nd SUV(max))/1st SUV(max) × 100. RESULTS: The change in SUVmax between baseline and interim PET/CT scans was significantly larger than between interim and preoperative PET/CT scan. An optimal cut-off ΔSUV value of 78.3% was proposed for discriminating patients with pCR from those without pCR. Metabolic CR, defined as a change of SUV(max) greater than the cut-off value, can predict pCR according to univariate analysis (p=0.012; Relative risk (RR)=25.3). Furthermore, metabolic CR was the most powerful factor for predicting pCR than other possible factors according to multivariate analysis (p=0.003). CONCLUSION: It is possible to use interim (18)F-FDG PET-CT as an effective method to predict early response in patients with breast cancer treated with neoadjuvant chemotherapy.

Expression patterns of glucose transporter-1 gene and thyroid specific genes in human papillary thyroid carcinoma.

PURPOSE: The expression of glucose transporter-1 (Glut-1) gene and those of major thyroid-specific genes were examined in papillary carcinoma tissues, and the expressions of these genes were compared with cancer differentiation grades. MATERIALS AND METHODS: Twenty-four human papillary carcinoma tissues were included in this study. The expressions of Glut-1- and thyroid-specific genes [sodium/iodide symporter (NIS), thyroid peroxidase, thyroglobulin, TSH receptor and pendrin] were analyzed by RT-PCR. Expression levels were expressed as ratios versus the expression of beta-actin. Pathologic differentiation of papillary carcinoma was classified into a relatively well-differentiated group (n = 13) and relatively less differentiated group (n = 11). RESULTS: Glut-1 gene expression was significantly higher in the less differentiated group (0.66 ± 0.04) than in the well-differentiated group (0.59 ± 0.07). The expression levels of the NIS, PD and TG genes were significantly higher in the well-differentiated group (NIS: 0.67 ± 0.20, PD: 0.65 ± 0.21, TG: 0.74 ± 0.16) than in the less differentiated group (NIS: 0.36 ± 0.05, PD: 0.49 ± 0.08, TG: 0.60 ± 0.11), respectively. A significant negative correlation was found between Glut-1 and NIS expression, and positive correlations were found between NIS and TG, and between NIS and PD. CONCLUSION: The NIS, PD and TG genes were highly expressed in well-differentiated thyroid carcinomas, whereas the Glut-1 gene was highly expressed in less differentiated thyroid carcinomas. These findings provide a molecular rationale for the management of papillary carcinoma, especially in the selection of FDG PET or radioiodine whole-body scan and I-131-based therapy.

The Clinical Role of Dual-Time-Point (18)F-FDG PET/CT in Differential Diagnosis of the Thyroid Incidentaloma.

Thyroid incidentalomas are common findings during imaging studies including (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) for cancer evaluation. Although the overall incidence of incidental thyroid uptake detected on PET imaging is low, clinical attention should be warranted owing to the high incidence of harboring primary thyroid malignancy. We retrospectively reviewed 2,368 dual-time-point (18)F-FDG PET/CT cases that were undertaken for cancer evaluation from November 2007 to February 2009, to determine the clinical impact of dual-time-point imaging in the differential diagnosis of thyroid incidentalomas. Focal thyroid uptake was identified in 64 PET cases and final diagnosis was clarified with cytology/histology in a total of 27 patients with (18)F-FDG-avid incidental thyroid lesion. The maximum standardized uptake value (SUVmax) of the initial image (SUV1) and SUVmax of the delayed image (SUV2) were determined, and the retention index (RI) was calculated by dividing the difference between SUV2 and SUV1 by SUV1 (i.e., RI = [SUV2 - SUV1]/SUV1 × 100). These indices were compared between patient groups that were proven to have pathologically benign or malignant thyroid lesions. There was no statistically significant difference in SUV1 between benign and malignant lesions. SUV2 and RI of the malignant lesions were significantly higher than the benign lesions. The areas under the ROC curves showed that SUV2 and RI have the ability to discriminate between benign and malignant thyroid lesions. The predictability of dual-time-point PET parameters for thyroid malignancy was assessed by ROC curve analyses. When SUV2 of 3.9 was used as cut-off threshold, malignancy on the pathology could be predicted with a sensitivity of 87.5 % and specificity of 75 %. A thyroid lesion that shows RI greater than 12.5 % could be expected to be malignant (sensitivity 88.9 %, specificity 66.3 %). All malignant lesions showed an increase in SUVmax on the delayed images compared with the initial images. But in the group of benign lesions, 37.5 % (6/16) showed a decrease or no change in SUVmax. Dual-time-point (18)F-FDG PET/CT, obtaining additional images 2 h after injection, seems to be a complementary method for the differentiation between malignancy and benignity of incidental thyroid lesions.

Prognostic impact of minimal pleural effusion in non-small-cell lung cancer.

PURPOSE: Minimal (< 10 mm thick) pleural effusion (PE) may represent an early phase of malignant PE, but its clinical relevance has rarely been studied. Therefore, we examined the proportion of minimal PE in patients with non-small-cell lung cancer (NSCLC) and its impact on survival. We also considered possible accumulation mechanisms in our data set. PATIENTS AND METHODS: On the basis of PE status from chest computed tomography scans at diagnosis, 2,061 patients were classified into three groups: no PE, minimal PE, and malignant PE. Twenty-one variables associated with four factors-patient, stage migration, tumor, and treatment-were investigated for correlation with survival. RESULTS: Minimal PE presented in 272 patients (13.2%). Of 2,061 patients, the proportion of each stage was the following: 5.2% stage I, 10.9% stage II, 13.2% stage IIIA, 23.8% stage IIIB, and 13.9% stage IV. Minimal PE correlated significantly with shorter survival time than did no PE (median survival time, 7.7 v 17.7 months; log-rank P < .001), even after full adjustment with all variables (adjusted hazard ratio, 1.40; 95% CI, 1.21 to 1.62). Prognostic impact of minimal PE was higher in early versus advanced stages (Pinteraction = .001). In 237 patients (87.8%) with minimal PE, pleural invasion or attachment as a direct mechanism was observed, and it was an independent factor predicting worse survival (P = .03). CONCLUSION: Minimal PE is a commonly encountered clinical concern in staging NSCLCs. Its presence is an important prognostic factor of worse survival, especially in early-stage disease.

Data sharing for public health research: A qualitative study of industry and academia.

Data sharing is a key biomedical research theme for the 21st century. Biomedical data sharing is the exchange of data among (non)affiliated parties under mutually agreeable terms to promote scientific advancement and the development of safe and effective medical products. Wide sharing of research data is important for scientific discovery, medical product development, and public health. Data sharing enables improvements in development of medical products, more attention to rare diseases, and cost-efficiencies in biomedical research. We interviewed 11 participants about their attitudes and beliefs about data sharing. Using a qualitative, thematic analysis approach, our analysis revealed a number of themes including: experiences, approaches, perceived challenges, and opportunities for sharing data.

Tetraspan TM4SF5-dependent direct activation of FAK and metastatic potential of hepatocarcinoma cells.

Transmembrane 4 L six family member 5 (TM4SF5) plays an important role in cell migration, and focal adhesion kinase (FAK) activity is essential for homeostatic and pathological migration of adherent cells. However, it is unclear how TM4SF5 signaling mediates the activation of cellular migration machinery, and how FAK is activated during cell adhesion. Here, we showed that direct and adhesion-dependent binding of TM4SF5 to FAK causes a structural alteration that may release the inhibitory intramolecular interaction in FAK. In turn, this may activate FAK at the cell's leading edge, to promote migration/invasion and in vivo metastasis. TM4SF5-mediated FAK activation occurred during integrin-mediated cell adhesion. TM4SF5 was localized at the leading edge of the cells, together with FAK and actin-organizing molecules, indicating a signaling link between TM4SF5/FAK and actin reorganization machinery. Impaired interactions between TM4SF5 and FAK resulted in an attenuated FAK phosphorylation (the signaling link to actin organization machinery) and the metastatic potential. Our findings demonstrate that TM4SF5 directly binds to and activates FAK in an adhesion-dependent manner, to regulate cell migration and invasion, suggesting that TM4SF5 is a promising target in the treatment of metastatic cancer.

Peripheral bone involvement of intravascular large B-cell lymphoma on 99mTc-MDP bone scan and 18F-FDG PET/CT.

A 64-year-old man was admitted for evaluation of recently developed anemia and bone pain. The bone scan showed diffusely active lesions in the peripheral bones, symmetrically. Interestingly, 18F-FDG PET/CT revealed the hypermetabolic changes in the peripheral bones as well as the internal organs. Biopsy of bone marrow confirmed the diagnosis of intravascular B-cell lymphoma. After the 3 cycles of R-CHOP chemotherapy, 18F-FDG PET/CT showed improvement of the previous hypermetabolic lesions, suggesting good response. Intravascular B-cell lymphoma is a rare and aggressive variant of diffuse large cell lymphoma characterized by proliferation of malignant cells within the vascular lumina.

Cross-talk between TGFß1 and EGFR signalling pathways induces TM4SF5 expression and epithelial-mesenchymal transition.

The EMT (epithelial-mesenchymal transition) is involved in fibrosis and cancer, and is regulated by different signalling pathways mediated through soluble factors, actin reorganization and transcription factor actions. Because the tetraspan (also called tetraspanin) TM4SF5 (transmembrane 4 L6 family member 5) is highly expressed in hepatocellular carcinoma and induces EMT, understanding how TM4SF5 expression in hepatocytes is regulated is important. We explored the mechanisms that induce TM4SF5 expression and whether impaired signalling pathways for TM4SF5 expression inhibit the acquisition of mesenchymal cell features, using human and mouse normal hepatocytes. We found that TGFß1 (transforming growth factor ß1)-mediated Smad activation caused TM4SF5 expression and EMT, and activation of the EGFR [EGF (epidermal growth factor) receptor] pathway. Inhibition of EGFR activity following TGFß1 treatment abolished acquisition of EMT, suggesting a link from Smads to EGFR for TM4SF5 expression. Further, TGFß1-mediated EGFR activation and TM4SF5 expression were abolished by EGFR suppression or extracellular EGF depletion. Smad overexpression mediated EGFR activation and TM4SF5 expression in the absence of serum, and EGFR kinase inactivation or EGF depletion abolished Smad-overexpression-induced TM4SF5 and mesenchymal cell marker expression. Inhibition of Smad, EGFR or TM4SF5 using Smad7 or small compounds also blocked TM4SF5 expression and/or EMT. These results indicate that TGFß1- and growth factor-mediated signalling activities mediate TM4SF5 expression leading to acquisition of mesenchymal cell features, suggesting that TM4SF5 induction may be involved in the development of liver pathologies.

Sulfur mustard primes human neutrophils for increased degranulation and stimulates cytokine release via TRPM2/p38 MAPK signaling.

Sulfur mustard (2,2'-bis-chloroethyl-sulfide; SM) has been a military threat since the World War I. The emerging threat of bioterrorism makes SM a major threat not only to military but also to civilian world. SM injury elicits an inflammatory response characterized by infiltration of neutrophils. Although SM was reported to prime neutrophils, the mechanism has not been identified yet. In the present study, we investigated the mechanism of SM-induced priming in human neutrophils. SM increased [Ca(2+)](i) in human neutrophils in a concentration-dependent fashion. Transient receptor potential melastatin (TRPM) 2 inhibitors (clotrimazole, econazole and flufenamic acid) and silencing of TRPM2 by shRNA attenuated SM-induced [Ca(2+)](i) increase. SM primed degranulation of azurophil and specific granules in response to activation by fMLP as previously reported. SB203580, an inhibitor of p38 MAPK, inhibited SM-induced priming. Neither PD98057, an ERK inhibitor, nor SP600215, a JNK inhibitor, inhibited SM-induced priming. In addition, SM enhanced phosphorylation of NF-kB p65 and release of TNF-α, interleukin (IL)-6 and IL-8. SB203580 inhibited SM-induced NF-kB phosphorylation and cytokine release. These results suggest the involvement of TRPM2/p38 MAPK pathway in SM-induced priming and cytokines release in neutrophils.