Magnolol Suppresses ERK/NF-κB Signaling and Triggers Apoptosis Through Extrinsic/Intrinsic Pathways in Osteosarcoma.

BACKGROUND/AIM: Osteosarcoma is an aggressive primary malignant bone tumor that occurs in childhood. Although the diagnostic and treatment options have been improved, osteosarcoma confers poor prognosis. Magnolol, an active component of Magnoliae officinalis cortex, has been widely applied in herb medicine and has been shown to have multiple pharmacological activities. However, whether magnolol possesses anti-osteosarcoma capacity remains unknown. MATERIALS AND METHODS: We examined magnolol is cytotoxicity, and whether it regulates apoptosis and oncogene expression using MTT, flow cytometry and Western blotting assays in osteosarcoma cells. RESULTS: Magnolol exerted toxicity towards U-2 OS cells by inducing intrinsic/extrinsic apoptosis pathways. Additionally, treatment of U-2 OS cells with magnolol inhibited MAPK1 mitogen-activated protein kinase 1 (ERK)/Nuclear factor kappa B (NF-B) signaling involved in tumor progression and reduced the expression of anti-apoptotic and metastasis-associated genes. CONCLUSION: Magnolol may induce apoptosis and inactivate ERK/NF-B signal transduction in osteosarcoma cells.

Reinforcement of Sorafenib Anti-osteosarcoma Effect by Amentoflavone Is Associated With the Induction of Apoptosis and Inactivation of ERK/NF-κB.

BACKGROUND/AIM: Sorafenib has been reported to show anti-osteosarcoma (anti-OS) efficacy by inhibiting metastasis; however, a phase II trial suggested that further combination with other agents could be necessary to achieve permanent remission. Herein, we aimed to identify whether amentoflavone, an abundant natural bioflavonoid found in many medicinal plants, can improve the treatment efficacy of sorafenib in OS. MATERIALS AND METHODS: Cell viability, metastasis, apoptosis, and nuclear translocation of NF-κB after amentoflavone combined with sorafenib were assayed by MTT, transwell migration/invasion, western blotting, flow cytometry, and immunofluorescence staining, respectively. RESULTS: The sorafenib-induced cytotoxicity and apoptosis of U-2 OS was enhanced by combining treatment with QNZ (NF-κB inhibitor) or amentoflavone. NF-κB nuclear translocation, NF-κB phosphorylation, and metastasis capacity of U-2 OS cells were inhibited by amentoflavone combined with sorafenib. CONCLUSION: Amentoflavone may sensitize OS to sorafenib treatment by inducing intrinsic and extrinsic apoptosis and inhibiting ERK/NF-κB signaling transduction.

The psychometric properties of the cervical nonorganic signs in patients with neck pain: an assessment of pain expression.

PURPOSE: Neck pain is a common cause of disability. This study investigated the psychometric properties of the cervical nonorganic signs (CNOS), a tool for assessing abnormal illness behaviors in patients with neck pain. METHODS: The CNOS was administered on patients with neck pain. Reliability and validity analyses were used to evaluate the psychometric properties. Exploratory factor analysis was used to investigate the dimensionality. Correlations with the Short Form-36 were used to investigate the convergent validity. RESULTS: The results supported the reliability (inter-rater reliability intra-class correlation: 0.920), validity (correlated with body pain (|ρ|=0.31) and vitality (|ρ| =0.30), and two-factor dimensionality (χ2= 5.904, p= 0.66; χ2/df = 0.738; RMSEA< 0.001; CFI = 1.000; TLI = 1.024; SRMR = 0.047) of the scale. The two factors were pain (severe pain) and vitality (poor vitality) expressed by the patients. CONCLUSION: The CNOS is a reliable and valid instrument for assessing pain and vitality problems. It helps patients to express severe pain and lack of vitality. The rehabilitation discipline could use the scale to understand pain expression and to design proper rehabilitation programs. Implications for Rehabilitation The cervical nonorganic signs has two domains (pain and vitality). The scale is reliable and valid for patients with neck pain. Patients with high scores on the pain domain have severe body pain that may interfere with normal social activities. Clinicians should understand their suffering and try to help them to alleviate the pain.

Correlations between quality of life and psychological factors in patients with chronic neck pain.

The purpose of this study was to investigate health-related quality of life (HRQOL) and associated factors in patients with chronic neck pain (CNP). The HRQOL of patients with CNP was assessed by the Short Form-36 questionnaire in this cross-sectional study. To evaluate the psychological factors related to HRQOL, the Eysenck Personality Questionnaire, Chinese Health Questionnaire, and Beck Anxiety Inventory were used. The scores for the eight subscales of Short Form-36 were all lower than the Taiwanese age-matched normative values (p < 0.001). The two most strongly affected subscales were the role-physical subscale and the bodily pain subscale; both scores were below half the score of the age-/sex-matched normative values. The physical components summary score, a summary measure, was moderately correlated with age (rho = -0.43), education level (rho = 0.37) and Beck Anxiety Inventory score (rho = -0.36). The mental components summary score was moderately to highly correlated with the Chinese Health Questionnaire score (rho = -0.72), the neuroticism domain of Eysenck Personality Questionnaire (rho = -0.52) and Beck Anxiety Inventory score (rho = -0.41). The HRQOL of patients with CNP was worse than that of normal subjects across all domains. Furthermore, patients with a neurotic personality, minor psychiatric morbidity and higher anxiety status showed poor mental health, as measured by the Short Form-36. We found that patients with CNP had multiple physical and mental health problems in terms of. The mental health of patients with CNP was strongly associated with various psychological factors. Comprehensive assessment of the physical and mental functioning of patients with CNP can improve the management and care of these patients.

Measurement of the functional status of patients with different types of muscular dystrophy.

Muscular dystrophy (MD) comprises a group of diseases characterized by progressive muscle weakness that induces functional deterioration. Clinical management requires the use of a well-designed scale to measure patients' functional status. This study aimed to investigate the quality of the functional scales used to assess patients with different types of MD. The Brooke scale and the Vignos scale were used to grade arm and leg function, respectively. The Barthel Index was used to evaluate the function of daily living activity. We performed tests to assess the acceptability of these scales. The characteristics of the different types of MD are discussed. This was a multicenter study and included patients diagnosed with Duchenne muscular dystrophy (DMD) (classified as severely progressive MD), Becker muscular dystrophy (BMD), limb girdle muscular dystrophy (LGMD) and facioscapulohumeral muscular dystrophy (FSHD). BMD, LGMD, and FSHD were classified as slowly progressive MD. The results demonstrated that the Brooke scale was acceptable for grading arm function in DMD, but was unable to discriminate between differing levels of severity in slowly progressive MD. The floor effect was large for all types of slowly progressive MD (range, 20.0-61.9), and was especially high for BMD. The floor effect was also large for BMD (23.8%) and FSHD (50.0%) using the Vignos scale. Grades 6-8 of the Vignos scale were inapplicable because they included items involving the use of long leg braces for walking or standing, and some patients did not use long leg braces. In the Barthel Index, a ceiling effect was prominent for slowly progressive MD (58.9%), while a floor effect existed for DMD (17.9%). Among the slowly progressive MDs, FSHD patients had the best level of functioning; they had better leg function and their daily living activities were less affected than patients with other forms of slowly progressive MD. The results of this study demonstrate the acceptability of the different applications used for measuring functional status in patients with different types of MD. Some of the limitations of these measures as applied to MD should be carefully considered, especially in patients with slowly progressive MD. We suggest that these applications be used in combination with other measures, or that a complicated instrument capable of evaluating the various levels of functional status be used.

Development and validation of a muscular dystrophy-specific functional rating scale.

OBJECTIVE: To develop a reliable and valid new rating scale for measuring the functional impact of muscular dystrophy. DESIGN: Prospective and longitudinal investigation. SETTING: Three academic medical centres in Taiwan and the Muscular Dystrophy Association of Taiwan. MEASURES: The Brooke Scale, the Vignos Scale, the Barthel Index, muscular strength, contracture severity, and predicted forced vital capacity (FVC%). METHODS: Scale development was in three stages. In stage I, a preliminary pool of 53 items was generated from patient interviews (n = 25), literature review, existing functional rating scales and expert opinion. In stage II, these items were administered to 85 patients with muscular dystrophy. The resulting data were analysed to construct a rating scale (the Muscular Dystrophy Functional Rating Scale, MDFRS) that encompassed four unidimensional constructs: mobility, basic activities of daily living, arm function and impairment. In stage III, the measurement properties of this rating scale were assessed in 121 muscular dystrophy patients different from those examined with the preliminary instrument. RESULTS: Internal consistency reliability was excellent for all domains of the final 33-item scale, with values of Cronbach's alpha ranging from 0.84 to 0.97. Intraclass correlation coefficients for test-retest and inter-rater reliability were 0.99 for all domains of the MDFRS. The MDFRS showed moderate to high correlations with a range of functional rating scales measuring similar aspects and impairment parameters (Spearman's rho = 0.65-0.91; P < 0.001, each). Confirmatory factor analysis supported a unitary construct of the four-dimensional MDFRS. The MDFRS had small floor and ceiling effects in the study samples. Sensitivity to change was confirmed by large standardized response means for the MDFRS total score. CONCLUSIONS: The MDFRS is a reliable and valid disease-specific measure of functional status for patients with muscular dystrophy.

Organization and expression of nitrogen-fixation genes in the aerobic nitrogen-fixing unicellular cyanobacterium Synechococcus sp. strain RF-1.

Sixteen nif and 'nif-associated' genes (expressed only under conditions of nitrogen fixation) in Synechococcus sp. strain RF-1 have been cloned and sequenced. All of the nif and nif-associated genes identified in Synechococcus RF-1 were arranged in a continuous cluster spanning approximately 18 kb and containing seven operons. The nifH operon (nifH-nifD-nifK) has been reported previously. nifB, fdxN, nifS, nifU and nifP were found to be located upstream of the nifH operon. nifB-fdxN-nifS-nifU were expressed as an operon. A nifP-like gene was found to be located just upstream of nifB. nifE, nifN, nifX, nifW and the nif-associated hesA, hesB and 'fdx' were found to be located downstream from nifK. The genes located downstream from nifK are arranged nifE-nifN-nifX-orf-nifW-hesA-hesB-'+ ++fdx' and span approximately 7 kb. The function of the ORF situated between nifX and nifW is not known. However, it was identified as a counterpart of ORF-2 in Anabaena sp. strain PCC 7120 based on the deduced amino acid sequence. Northern hybridization and primer extension analysis indicated that the nif and nif-associated genes are organized in nifE-nifN, nifX-orf, nifW-hesA-hesB and 'fdx'-containing operons, respectively. According to the results of this study and previous reports, the genes are expressed in a rhythmic pattern with peaks during the dark phase when the culture is grown in a 12 h light/12 h dark regimen. The rhythm persisted after the culture was transferred to continuous illumination.