Quiescin Sulfhydryl Oxidase 1 (QSOX1) Secreted by Lung Cancer Cells Promotes Cancer Metastasis.

As lung cancer shows the highest mortality in cancer-related death, serum biomarkers are demanded for lung cancer diagnosis and its treatment. To discover lung cancer protein biomarkers, secreted proteins from primary cultured lung cancer and adjacent normal tissues from patients were subjected to LC/MS⁻MS proteomic analysis. Quiescin sulfhydryl oxidase (QSOX1) was selected as a biomarker candidate from the enriched proteins in the secretion of lung cancer cells. QSOX1 levels were higher in 82% (51 of 62 tissues) of lung cancer tissues compared to adjacent normal tissues. Importantly, QSOX1 serum levels were significantly higher in cancer patients (p < 0.05, Area Under curve (AUC) = 0.89) when measured by multiple reaction monitoring (MRM). Higher levels of QSOX1 were also uniquely detected in lung cancer tissues, among several other solid cancers, by immunohistochemistry. QSOX1-knock-downed Lewis lung cancer (LLC) cells were less viable from oxidative stress and reduced migration and invasion. In addition, LLC mouse models with QSOX1 knock-down also proved that QSOX1 functions in promoting cancer metastasis. In conclusion, QSOX1 might be a lung cancer tissue-derived biomarker and be involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers.

The effect of changing condition of walking speed on the knee angle of rats with osteoarthritis.

[Purpose] The purpose of this study was to investigate the positive effect of exercise on knee osteoarthritis in rats with osteoarthritis induced by applying effective walking speed when changing speed conditions during walking. [Subjects and Methods] The rats used in this study were male Sprague-Dawley rats weighing 300 g and 7 weeks old, and 20 rats were used. The Osteoarthritis (OA) rats model was induced by MIA (monoiodoacetate). The rats was randomly divided into experimental group (MIA injection group) and control group (normal cell line injection group). Treadmill exercise was provided two groups for 2 weeks, 4 days per week. The knee joint angle of the stance was divided into pre-test and post-test, and each group was subjected to paired sample test. Independent sample t-test was conducted to examine the difference between experimental group and control group. [Results] There were statistically significant changes in the control and experimental groups. The knee angle was changed from 99.70 ± 2.40 to 85.60 ± 2.67 in the control group. The knee angle was changed from 100.96 ± 1.36 to 87.71 ± 1.57 in the experimental group. [Conclusion] In conclusion, the angle of the knee gradually decreases. It is considered a characteristic of progressive osteoarthritis. The change of knee angle was less in the experimental group than in the control group. This means that the stiffness of the joints during the walking exercise was less progressed in the experimental group than in the control group.

The relationship between non-affected forelimb exercise and recovery after focal cerebral ischemia in acute phase.

[Purpose] In the present study, we hypothesized that exercise of the nonaffected forelimb in the early poststroke phase would stimulate the intact hemisphere, thereby influencing the hemisphere of the infarcted side and improving the performance of the hemiplegic limb. [Subjects and Methods] Adult male Sprague-Dawley rats (8-10 weeks of age, weighing 250-300 g, n=12) were used and randomly divided into 3 groups: nonaffected forelimb exercise for 3 days and treadmill exercise 7 days after ischemia (ETF, n=6), resting for 3 days and treadmill exercise 7 days after ischemia (ETN, n=6), and after ischemia 10 days resting group. To validate nerve growth factor (NGF), western blot analysis was performed. The results were analyzed using SPSS for Windows version 18.0. and expressed as mean ± standard deviation (SD). [Results] Early treadmill exercise increased the expression of NGF protein level in both ETE and ETN groups. Comparing between the nonaffected forelimb exercise and infarct hemisphere in NGF protein expression, the ETE group showed higher increase of NGF protein level in right hemisphere than ETN group, but there was no statistical significance. [Conclusion] The early treadmill exercise increased NGF protein expression levels in both hemispheres and the nonaffected forelimb exercise in the early poststroke recovery phase could enhance neuronal recovery after focal ischemia in rat models.

The effect of the inspiratory muscle training on functional ability in stroke patients.

[Purpose] This study was to find out an inspiratory muscle training (IMT) program therapeutic effects on stroke patients' functional ability. [Subjects and Methods] Twenty stroke patients were assigned to one of two groups: inspiratory muscle training (n=10), and control (n=10), randomization. The inspiratory muscle training participants undertook an exercise program for 30 minute per times, 5 times a week for 6 weeks. The investigator measured the patients' trunk impairment scale (TIS) and 6 minute walking test (6MW) for functional ability before and after IMT. [Results] The TIS appeared some significant differences in both groups before and after the training. The 6MW test showed some significant differences in the inspiratory muscle training group, but didn't show any significant difference in the control group. And the differences in both groups after depending the inspiratory muscle training were significantly found in the tests of TIS and 6MW test [Conclusion] The results showed that the inspiratory muscle training in stroke patients are correlated with the trunk stability and locomotion ability, suggesting that physical therapist must take into consideration the inspiratory muscle training, as well as functional training to improve physical function in stroke patients.

Stanniocalcin-2 (STC2): A potential lung cancer biomarker promotes lung cancer metastasis and progression.

The homodimeric glycoprotein, stanniocalcin 2 (STC2) is previously known to be involved in the regulation of calcium and phosphate transport in the kidney and also reported to play multiple roles in several cancers. However, its function and clinical significance in lung cancer have never been reported and still remain uncertain. Here, we investigated the possibility of STC2 as a lung cancer biomarker and identified its potential role in lung cancer cell growth, metastasis and progression. Proteomic analysis of secretome of primary cultured lung cancer cells revealed higher expression of STC2 in cancers compared to that of adjacent normal cells. RT-PCR and Western blot analyses showed higher mRNA and protein expressions of STC2 in lung cancer tissues compared to the adjacent normal tissues. Knockdown of STC2 in H460 lung cancer cells slowed down cell growth progression and colony formation. Further analysis revealed suppression of migration, invasion and delayed G0/G1 cell cycle progression in the STC2 knockdown cells. STC2 knockdown also attenuated the H202-induced oxidative stress on H460 cell viability with a subsequent increase in intracellular ROS levels, which suggest a protective role of STC2 in redox regulatory system of lung cancer. These findings suggest that STC2 can be a potential lung cancer biomarker and plays a positive role in lung cancer metastasis and progression. This article is part of a Special Issue entitled: Medical Proteomics.

The effects of exercise on the GAP-43 expression in the spinal cord of arthritis-induced rats.

[Purpose] The purpose of the study was to investigate the effects of exercise on the recovery of spinal cord nerve cells damaged due to pain signals which are a major symptom of osteoarthritis. [Subjects and Methods] Adult male Sprague-Dawley rats (n=40) were used and induction of osteoarthritis by monosodium iodoacetate. Injected rats were randomly divided into 4 groups: Sham control group without MIA injection (SG), control group with injected MIA (CG), OA without exercise (NEG), OA with exercise (EG). Sham control group was injected normal cell line instead of MIA. The exercise group was submitted to 4-week training program on a treadmill for 5 days/week, 30 min/day, 16 m/min velocity, then spinal cord were removed and measured the GAP-43 expression by immunohistochemistry analysis. [Results] In this study, a results of measuring the expression of GAP-43. GAP-43 was observed in all groups, showed that the significant difference in each group. [Conclusion] It could be seen that exercise increased the GAP-43 expression in the spinal cord to promote the recovery of spinal cord nerve cells damaged due to chronic osteoarthritis.

The effect of low-intensity laser therapy (LILT) on cutaneous wound healing and pain relief in rats.

[Purpose] This study examined the impact of low-intensity laser therapy on wound healing and pain control using a rat cutaneous wound model. [Subjects and Methods] Twenty-four adult male Sprague-Dawley rats (between 220-240 g, 7 weeks) were used in this study. The rats were anesthetized and a circular fragment of skin was removed from the dorsal region of the back by a punch with an 8-mm diameter. The animals were randomly divided into 6 groups, Groups C 1, C 3, and C 5, control groups, received no laser treatment. Groups T 1, T 3, and T 5 received laser treatment for 20 min per day for 1, 3 and 5 days, respectively. Lumbar spine and dorsal skin were extracted and processed using western blot analysis. [Results] Periodical observation showed increases in NGF expression on the skin, and decreases in c-fos expression by the spinal cord in the treatment groups compared to the control group. [Conclusion] The present findings suggest that low-intensity laser therapy could be used as an effective therapy for wound healing and pain relief, and could be further used as a clinical approach for treating cutaneous wounds.

Effect of exercise on the expression of nerve growth factor in the spinal cord of rats with induced osteoarthritis.

[Purpose] We examined the impact of exercise on the expression pattern of nerve growth factor in the spinal cord of rats with induced osteoarthritis of the knee joint. [Subjects and Methods] To produce monosodium iodoacetate-induced arthritis, rats were administered 3 mg/50 µL monosodium iodoacetate through the interarticular space of the right knee. The animals were randomly divided into four groups: rats sacrificed 3 weeks after 0.9% saline solution injection (shame group, n = 10), rats sacrificed 3 weeks after monosodium iodoacetate injection (control group, n = 10), rats with 4 weeks rest from 3 weeks after monosodium iodoacetate injection (no exercise group, n = 10), and rats with 4 weeks treadmill training from 3 weeks after monosodium iodoacetate injection (exercise group, n = 10). Serial coronal sections of the lumbar spine were cut and processed for immunohistochemistry. [Results] The expression of nerve growth factor was significantly increased in the EG compared with the SG, CG, and NEG. [Conclusion] Increased nerve growth factor expression in the spinal cord due to exercise-induced stimulation can be effective in treating chronic pain. Such treatment will contribute not only to improving the joint function of patients with chronic pain but also their quality of life.

The effect of trunk stabilization exercises with a swiss ball on core muscle activation in the elderly.

[Purpose] The purpose of this study was to investigate the effects of trunk stabilization exercise on the muscle EMG activations related to core stability. [Subjects and Methods] Fifteen elderly people in a geriatric hospital performed trunk stabilization exercises with a Swiss ball for 20 minutes five times per week for 8 weeks. Trunk muscle activations were measured using electromyography before and after the intervention. [Results] After the intervention, the muscle activations of the rectus abdominis, erector spinae, lateral low-back (quadratus lumborum and external oblique), and gluteus medius muscles increased significantly. [Conclusion] The trunk stabilization exercise with a Swiss ball significantly increased the muscle activities of the elderly.

The effects of hippotherapy and a horse riding simulator on the balance of children with cerebral palsy.

[Purpose] We with respect to their effects on the compared hippotherapy with a horseback riding simulator (JOBA, Panasonic Inc. JP) static and dynamic balance of children with cerebral palsy (CP). [Subjects and Methods] Twenty-six children were randomly divided into two groups: a hippotherapy group that included 13 children, and a horseback riding simulator (JOBA, Panasonic Inc., Japan) group, which was also composed of 13 children. The two groups participated in 1 hour of exercise per day, 3 times a week, for 12 weeks. The subjects' static balance ability was measured using BPM (software 5.3, SMS Healthcare Inc., UK) as the center of pressure sway length while standing for 30 seconds with their eyes open and looking to the front. Dynamic balance ability was measured using the PBS (Pediatric Balance Scale). [Results] Both groups showed significant improvements in static and dynamic balance but significant differences between the two groups were not found. [Conclusion] The horseback riding simulator could be a useful alternative to hippotherapy for the improvement of static and dynamic balance of children with CP.

Study of treadmill exercise effect on rats with osteoarthritis using proteomic analysis.

[Purpose] To investigate the correlation between the effect treadmill exercise and change in serum proteins in rats with osteoarthritis, a study of proteins was carried out using a mass spectrometer. [Subjects and Methods] Rats were randomly divided into five groups. After 4 weeks of treadmill training, serum from each rat was analyzed by Liquid chromatography-electrospray ionization tandem mass spectrometry. Complementary component 9 (C9) was discovered to be downregulated in the serum of the exercise groups, and this was validated by Western blot. [Results] Seventeen proteins were discovered to be elevated in the monosodium iodoacetate injection osteoarthritis group samples by more than 1.5 fold compared with the control group. One of the proteins upregulated, C9 protein, was validated, and it was found to decrease in the middle-intensity exercise group. [Conclusion] We showed that the serum level of C9, an inflammatory-related protein, decreased after treadmill exercise. Therefore, treadmill exercise with an appropriate intensity might be recommended for OA patients.

The effect of proprioceptive neuromuscular facilitation therapy on pain and function.

[Purpose] The present study examined the effects of treatment using PNF extension techniques on the pain, pressure pain, and neck and shoulder functions of the upper trapezius muscles of myofascial pain syndrome (MPS) patients. [Subjects] Thirty-two patients with MPS in the upper trapezius muscle were divided into two groups: a PNF group (n=16), and a control group (n=16) [Methods] The PNF group received upper trapezius muscle relaxation therapy and shoulder joint stabilizing exercises. Subjects in the control group received only the general physical therapies for the upper trapezius muscles. Subjects were measured for pain on a visual analog scale (VAS), pressure pain threshold (PPT), the neck disability index (NDI), and the Constant-Murley scale (CMS). [Results] None of the VAS, PPT, and NDI results showed significant differences between the groups, while performing postures, internal rotation, and external rotation among the CMS items showed significant differences between the groups. [Conclusion] Exercise programs that apply PNF techniques can be said to be effective at improving the function of MPS patients.

Meta-markers for the differential diagnosis of lung cancer and lung disease.

UNLABELLED: Misdiagnosis of lung cancer remains a serious problem due to the difficulty of distinguishing lung cancer from other respiratory lung diseases. As a result, the development of serum-based differential diagnostic biomarkers is in high demand. In this study, 198 clinical serum samples from non-cancer lung disease and lung cancer patients were analyzed using nLC-MRM-MS for the levels of seven lung cancer biomarker candidates. When the candidates were assessed individually, only SERPINEA4 showed statistically significant changes in the serum levels. The MRM results and clinical information were analyzed using a logistic regression analysis to select model for the best 'meta-marker', or combination of biomarkers for differential diagnosis. Also, under consideration of statistical interaction, variables having low significance as a single factor but statistically influencing on meta-marker model were selected. Using this probabilistic classification, the best meta-marker was determined to be made up of two proteins SERPINA4 and PON1 with age factor. This meta-marker showed an enhanced differential diagnostic capability (AUC=0.915) for distinguishing the two patient groups. Our results suggest that a statistical model can determine optimal meta-markers, which may have better specificity and sensitivity than a single biomarker and thus improve the differential diagnosis of lung cancer and lung disease patients. BIOLOGICAL SIGNIFICANCE: Diagnosing lung cancer commonly involves the use of radiographic methods. However, an imaging-based diagnosis may fail to differentiate lung cancer from non-cancerous lung disease. In this study, we examined several serum proteins in the sera of 198 lung cancer and non-cancerous lung disease patients by multiple-reaction monitoring. We then used a combination of variables to generate a meta-marker model that is useful as a differential diagnostic biomarker.

Stanniocalcin 2 enhances mesenchymal stem cell survival by suppressing oxidative stress.

To overcome the disadvantages of stem cell-based cell therapy like low cell survival at the disease site, we used stanniocalcin 2 (STC2), a family of secreted glycoprotein hormones that function to inhibit apoptosis and oxidative damage and to induce proliferation. STC2 gene was transfected into two kinds of stem cells to prolong cell survival and protect the cells from the damage by oxidative stress. The stem cells expressing STC2 exhibited increased cell viability and improved cell survival as well as elevated expression of the pluripotency and self-renewal markers (Oct4 and Nanog) under sub-lethal oxidative conditions. Up-regulation of CDK2 and CDK4 and down-regulation of cell cycle inhibitors p16 and p21 were observed after the delivery of STC2. Furthermore, STC2 transduction activated pAKT and pERK 1/2 signal pathways. Taken together, the STC2 can be used to enhance cell survival and maintain long-term stemness in therapeutic use of stem cells.