Anti-Cancer Effects of Oxygen-Atom-Modified Derivatives of Wasabi Components on Human Leukemia Cells.

1-Isothiocyanato-6-(methylsulfinyl)-hexanate (6-MITC) is a natural compound found in Wasabia japonica. The synthetic derivatives 1-Isothiocyanato-6-(methylsulfenyl)-hexane (I7447) and 1-Isothiocyanato-6-(methylsulfonyl)-hexane (I7557) were obtained from 6-MITC by deleting and adding an oxygen atom to the sulfone group, respectively. We previously demonstrated that extensive mitotic arrest, spindle multipolarity, and cytoplasmic vacuole accumulation were induced by 6-MITC and inhibited the viability of human chronic myelogenous leukemia K562 cells. In this study, we examined the anti-cancer effects of 6-MITC derivatives on human chronic myelogenous leukemia (CML) cells. Autophagy was identified as the formation of autophagosomes with double-layered membranes using transmission electron microscopy. Cell cycle and differentiation were analyzed using flow cytometry. Apoptosis was detected by annexin V staining. After treatment with I7447 and I7557, the G2/M phase of cell cycle arrest was revealed. Cell death can be induced by a distinct mechanism (the simultaneous occurrence of autophagy and aberrant mitosis). The expression levels of acridine orange were significantly affected by lysosomal inhibitors. The natural wasabi component, 6-MITC, and its synthetic derivatives have similar effects on human chronic myelogenous leukemia cells and may be developed as novel therapeutic agents against leukemia.

Borneol and Tetrandrine Modulate the Blood-Brain Barrier and Blood-Tumor Barrier to Improve the Therapeutic Efficacy of 5-Fluorouracil in Brain Metastasis.

The efficacy of chemotherapeutic drugs for the treatment of brain metastasis may be compromised by the blood-brain barrier (BBB) and blood-tumor barrier (BTB). P-glycoprotein (P-gp) is a multidrug resistance protein that potentially limits the penetration of chemotherapeutics through the BBB and BTB. 5-Fluorouracil (5-FU) is widely used to treat cancer. Bioactive constituents of medicinal herbs, such as borneol and tetrandrine, potentially improve drug penetration through the BBB and BTB. We hypothesized that borneol and tetrandrine might modulate the BBB and BTB to enhance 5-FU penetration into the brain. To investigate this, in vitro and in vivo models were developed to explore the modulatory effects of borneol and tetrandrine on 5-FU penetration through the BBB and BTB. In the in vitro models, barrier integrity, cell viability, barrier penetration, P-gp activity, and NF-κB expression were assessed. In the in vivo brain metastasis models, cancer cells were injected into the internal carotid artery to evaluate tumor growth. The experimental results demonstrated that borneol and borneol + tetrandrine reduced BBB integrity. The efflux pump function of P-gp was partially inhibited by tetrandrine and borneol + tetrandrine. In the in vivo experiment, borneol + tetrandrine effectively prolonged survival without compromising body weight. In conclusion, BBB and BTB integrity was modulated by borneol and borneol + tetrandrine. The combination of borneol and tetrandrine could be used to improve the chemotherapeutic control of brain metastasis.

Ventilator Parameters in the Diagnosis and Prognosis of Acute Respiratory Distress Syndrome in Postoperative Patients: A Preliminary Study.

This study investigated the usefulness of ventilator parameters in the prediction of development and outcome of acute respiratory distress syndrome (ARDS) in postoperative patients with esophageal or lung cancer on admission to the surgical intensive care unit (SICU). A total of 32 post-operative patients with lung or esophageal cancer from SICU in a tertiary medical center were retrospectively analyzed. The study patients were divided into an ARDS group (n = 21) and a non-ARDS group (n = 11). The ARDS group contained the postoperative patients who developed ARDS after lung or esophageal cancer surgery. The ventilator variables were analyzed in this study. Principal component analysis (PCA) was performed to reduce the correlated ventilator variables to a small set of variables. The top three ventilator variables with large coefficients, as determined by PCA, were considered as sensitive variables and included in the analysis model based on the rule of 10 events per variable. Firth logistic regression with selective stepwise elimination procedure was performed to identify the most important predictors of morbidity and mortality in patients with ARDS. Ventilator parameters, including rapid shallow breath index during mechanical ventilation (RSBIv), rate pressure product of ventilation (RPPv), rate pressure volume index (RPVI), mechanical work (MW), and inspiration to expiration time ratio (IER), were analyzed in this study. It was found that the ARDS patients had significantly greater respiratory rate (RR), airway resistance (Raw), RSBIv, RPPv, RPVI, positive end-expiratory pressure (PEEP), and IER and significantly lower respiratory interval (RI), expiration time (Te), flow rate (V˙), tidal volume (VT), dynamic compliance (Cdyn), mechanical work of ventilation (MW), and MW/IER ratio than the non-ARDS patients. The non-survivors of ARDS had significantly greater peak inspiratory pressure above PEEP (PIP), RSBIv, RPPv, and RPVI than the survivors of ARDS. By using PCA, the MW/IER was found to be the most important predictor of the development of ARDS, and both RPPv and RPVI were significant predictors of mortality in patients with ARDS. In conclusion, some ventilator parameters, such as RPPv, RPVI, and MW/IER defined in this study, can be derived from ventilator readings and used to predict the development and outcome of ARDS in mechanically ventilated patients on admission to the SICU.

Inhibition of Jurkat T Cell Growth by N-farnesyl-norcantharimide Through Up-regulation of Tumor Suppressor Genes and Down-regulation of Genes for Steroid Biosynthesis, Metabolic Pathways and Fatty Acid Metabolism.

BACKGROUND/AIM: To evaluate the anti-cancer mechanism of N-Farnesyl-norcantharimide (NC15). MATERIALS AND METHODS: The viability of NC15-treated human leukemic Jurkat T (JKT) cells was assessed using the Kit-8 cell counting method. Flow cytometry analysis, human apoptosis antibody array assay, and whole genome sequencing were adopted to investigate the mechanism underlying the anti-cancer activity of NC15 in JKT cells. RESULTS: The growth inhibition rates of NC15 in JKT cells were about 80% and 95% after treatment with 8 µmol/l NC15 for 24 and 48 h, respectively. The percentages of NC15-treated JKT cells in the sub-G1 phase at 24 and 48 h were 22.0% and 34.3%, respectively, in contrast to the 1.5% in the control. Next-generation sequencing showed that many tumor suppressor genes (TSG) were up-regulated, while many genes associated with steroid biosynthesis, metabolic pathways, and fatty acid metabolism were down-regulated. CONCLUSION: NC15 can reduce the cell viability and increase the percentage of JKT cells in the sub-G1 phase by up-regulating TSG and related genes, and down-regulating the genes for steroid biosynthesis, metabolic pathways and fatty acid metabolism, instead of through apoptosis.

Effect of body position on bilateral EEG alterations and their relationship with autonomic nervous modulation in normal subjects.

This study investigated the effect of body position on the electroencephalogram (EEG) and autonomic nervous modulation, and the relationship between them using spectral analysis of EEG and heart rate variability (HRV). All healthy volunteers recruited had their electrocardiogram and EEG recorded for power spectral analysis. We found that when changing position from supine to upright, the EEG spectral components below the α band, such as δ and θ bands, were significantly decreased while the EEG spectral components above the α band, such as ß, γ and ω bands, were significantly increased in both scalps. Correlation analysis showed that the θ rhythm of both scalps might be associated with the control of HR, the α and ß rhythms of right scalp might be associated with vagal modulation, and the γ rhythm of left scalp might be associated with sympathetic modulation of the subject. Thus, some EEG components might be associated with the autonomic nervous modulation of the subject during positional change. There might be a mechanism located in the brain-stem which jointly controls both autonomic influences on heart rate and EEG activation.

Cerebral sinus thrombosis with intracerebral hemorrhage in pregnancy: a case report.

A 29-year-old woman who was pregnant for 12 weeks presented with headache for one week and drowsiness for two days. Computed tomography of the brain revealed multifocal hematomas with mass effect. Decompressive craniectomy was done to relieve the increased intracranial pressure. Magnetic resonance angiography and cerebral angiography were subsequently performed, both demonstrating thrombosis of the left transverse sinus. Treatment of sinus thrombosis generally includes correction of increased intracranial pressure and administration of anticoagulants, such as heparin. However, in this case heparin was contraindicated for the presence of intracranial bleeding, a clinical dilemma that requires careful considerations to balance treatment risks and benefits.

Vicarious perception of postural discomfort and exertion.

Perceived exertion and discomfort have been used extensively in ergonomics practice. Job incumbents typically rate their exertion on scales such as Borg's rated perceived effort (RPE) and their discomfort on scales such as Corlett and Bishop's body part discomfort scales (BPD). This study asks whether exertion and discomfort can be perceived by an external observer, i.e. is vicarious perception possible? Four participants (targets) performed 20 postural holding tasks selected from Ovako Working Posture Analysing System postures and gave RPE and BPD scores for each posture. Video clips of each target in each posture were shown to four expert ergonomists and 23 novices, who also gave RPE and BPD scores. Correlations between targets and observers scores were high, with significance exceeding p = 0.01. Observers were generally conservative, rating easy postures too high and difficult postures too low. All observers rated female targets higher than male targets. Female observers rated all targets higher then male observers. Vicarious perception of discomfort and exertion was possible, but there was not a one-to-one correspondence to ratings given by those experiencing the posture.

Tophaceous gout of the lumbar spine mimicking infectious spondylodiscitis and epidural abscess: MR imaging findings.

We report a case of surgically proven tophaceous gout of the lumbar spine at the L5-S1 level that mimicked infectious spondylodiscitis and epidural abscess on magnetic resonance (MR) images in a 65-year-old woman. The spinal tophi were hypointense on T1-weighted images; focally and strongly hyperintense on T2-weighted images; and heterogeneously, marginally enhancing on contrast-enhanced T1-weighted images. The aim of this report is to emphasize the importance of considering this disease entity in the differential diagnosis of an epidural mass in a patient with chronic back pain.

Cough induced by ossification of the ligamentum flavum in the high cervical spine. Case report.

The authors report a very rare case of high cervical ossification of the ligamentum flavum (OLF) in a 40-year-old woman who developed an intractable cough after a traffic accident. The patient's symptoms subsided immediately after decompressive laminectomy and removal of the lesion. To the authors' knowledge, this is the first reported case of high cervical OLF in a patient who presented with a cough. The pathophysiological mechanism underlying the cough was determined to be symptomatic of high cervical spine OLF.