GPAA1 promotes progression of childhood acute lymphoblastic leukemia through regulating c-myc.

OBJECTIVE: Previous studies have shown that glycosylphosphatidylinositol Anchor Attachment Protein 1 (GPAA1) is a cancer-promoting gene; however, the role of GPAA1 in childhood acute lymphoblastic leukemia (ALL) has not been reported. This study aims to illustrate the role of GPAA1 in promoting the metastasis of ALL by targeting c-myc and the potential mechanism. PATIENTS AND METHODS: Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to examine serum levels of GPAA1 and c-myc in 42 childhood ALL patients and healthy volunteers. The interaction between GPAA1 expression and prognosis of childhood ALL was analyzed. Meanwhile, expressions of GPAA1 and c-myc in ALL cell lines were determined by qRT-PCR. Furthermore, after GPAA1 knockdown model was constructed by lentivirus transfection in MOLT-4 and SUP-B15 cells, cell counting kit-8 (CCK-8), transwell invasion, and cell wound healing assays were conducted to analyze the effect of GPAA1 on the biological functions of ALL cells. Potential mechanism was further explored through Luciferase reporter gene assay and cell recovery experiments. RESULTS: QRT-PCR results indicated that serum level of GPAA1 in childhood ALL patients was remarkably higher than that of healthy volunteers, and the difference was statistically significant. Childhood ALL patients with high expression of GPAA1 had lower overall survival rate compared with those expressing low expression of GPAA1. Proliferation and metastasis abilities of pediatric ALL cells with GPAA1 knockdown remarkably decreased. Subsequently, c-myc expression was also found remarkably upregulated in ALL cell lines and serum samples of childhood ALL patients and it was positively correlated with GPAA1 level. In addition, Luciferase reporter gene assay demonstrated that overexpression of c-myc remarkably attenuated the Luciferase activity of the wild-type GPAA1 vector without attenuating that of the mutant vector or empty vector, further demonstrating that GPAA1 can be targeted by c-myc. At the same time, cell recovery experiment found that the interaction between GPAA1 and c-myc together regulated the malignant progression of ALL. CONCLUSIONS: GPAA1 was up-regulated in serum of childhood ALL patients, which was remarkably associated with the prognosis. In addition, GPAA1 may contribute to the malignant progression of childhood ALL via activating c-myc.

[Effect of magnesium and selenium on the expression of matrix metalloproteinases-20 and kallikrein 4 in fluorosis mice].

OBJECTIVE: To study the effect of magnesium/selenium on the expression of matrix metalloproteinases-20(MMP-20) and kallikrein 4(KLK4) during fluorosis in mice and to explore the formation mechanism of dental fluorosis. METHODS: Eighty SPF male ICR mice were randomly divided into 8 groups according to body weight: control group, magnesium group, selenium group, magnesium-selenium group, fluoride group, magnesium-fluorine group, selenium-fluorine group and magnesium-selenium-fluorine group. Mice in control, magnesium, selenium and magnesium-selenium groups were fed double steamed water, and mice in the other four groups were feddouble steamed water with 50 mg/L F(-). Mice in control and fluoride groups were fed conventionally. Mice in magnesium and magnesium-fluorine groups were fed conventionally by adding MgSO4·7H2O 162.5 mg/kg. Mice in selenium and selenium-fluorine groups were fed conventionally by adding Na2SeO3·5H2O 2 mg/kg. Mice in magnesium-selenium and magnesium-selenium-fluorine groups were fed conventionally by adding MgSO4·7 H2O 162.5 mg/kg + Na2SeO3·5H2O 2 mg/kg. Incisor specimens were obtained after the mice were put into death when they were 42 days. The expressions of MMP-20 and KLK4 were observed by using immunohisto-chemicalstain. RESULTS: The meangray value of MMP-20 of fluoride group(133.1±10.3) was significantly higher than that of control group(116.8±10.0), magnesium group (113.6 ± 9.6), magnesium-selenium group(108.2 ± 15.2), magnesium-fluorine group(111.1 ± 8.1) and magnesium-selenium-fluorine group(108.2 ± 11.0), respectively(F=3.864, P<0.05). The mean gray value of MMP-20 of magnesium-selenium-fluorine group(108.2±11.0) was significantly lower than that of selenium group(125.4 ± 7.9), fluoride group (133.1 ± 10.3) and selenium-fluorine group(126.2 ± 2.8), respectively(F= 3.864, P<0.05). The mean gray value of KLK4 of magnesium-selenium group(117.2±11.7) was significantly lower than others(137.3±7.9 of control group, 144.2±7.7 of magnesium group, 138.9±13.3 of selenium group, 149.7 ± 12.4 of fluoride group, 148.9 ± 7.5 of magnesium-fluorine group, 140.6 ± 17.0 of selenium-fluorine group and 140.7 ± 7.3 of magnesium-selenium-fluorine group, F=3.668, P<0.05). In factorial analysis of fluorosis mice, magnesium had effect on the expression of MMP-20(F=42.613, P<0.05), selenium had effect on the expression of KLK4(F=6.649, P<0.05). CONCLUSIONS: The excessive fluoride could inhibit the expressions of MMP-20. The excessive fluoride hadno significant influence on the expression of KLK4. Magnesium and selenium had antagonistic effect on the dental fluorosis.

Fibroblasts as novel therapeutic targets in chronic inflammation.

A characteristic feature of many chronic inflammatory diseases is their persistence and predilection for certain sites. The molecular basis for such tissue tropism and failure of the inflammatory response to resolve has until relative recently remained obscure. Recent studies have strongly implicated fibroblasts as cells which contribute to disease persistence and which help define anatomical location. Therefore fibroblasts make an attractive therapeutic target as they help orchestrate the inflammatory infiltrate. Current anti-inflammatory therapies target immune cells in an attempt to inhibit the production of pro-inflammatory mediators. However an equally important target is the active induction of pro-resolution programmes responsible for the resolution of inflammation. Fibroblasts are likely to be an important source of these anti-inflammatory mediators. Therapeutic manipulation of fibroblasts and their biologically active products is an emerging concept in treating cancer and is likely to provide a novel method to achieve improved control of chronic inflammatory disease.

Applied studies of the plant meridian system: II. Agri-wave technology increases the yield and quality of spinach and lettuce and enhances the disease resistant properties of spinach.

Agri-wave technology is composed of both a special frequency sound wave and a microelement fertilizer. In both components, the effect of sound waves on plants is more than that of fertilizers, but the best function is a combination of the two. Treatment by Agri-wave technology stimulated the growth rate and increased the yield of spinach. In small plot tests, the length and width of the treated spinach leaf was 50.8 cm and 20.3 cm, respectively, whereas the untreated leaves were 29.20 cm and 8.9 cm. The fresh weight of treated spinach was 0.42 kg. This was 5.5 times higher than that of the untreated spinach. In large area testing (17 hectares), the results of two tests show that the yields of the treated spinach were increased 22.7% and 22.2% over those of the control group. Sugar content of the treated spinach was increased by 37.5%, vitamin A, C, and B were increased 35.63%, 41.67% and 40.00%, respectively, above the levels of the control group. Niacin content was decreased by 7.69%. Of 33 elements analyzed in the spinach, 29 elements were increased by Agri-wave technology. The spinach was infected with "rot disease" in the control group while there was no disease present in the treated group. In greenhouse testing, the average weight of 3 species of lettuce treated by Agri-wave technology was increased 44.10% over that of the control group (P < 0.0001). The average weight of 3 species of lettuce by only sound and only fertilizer treated separately increased 29.92% and 16.19% above that of the control group (P < 0.0001). Sampling survey results in the field test were comparable to the above mentioned greenhouse test. The fresh weight of treated lettuce by Agri-wave technology was increased 41.67% over that of the control group (P < 0.0001). The fresh weight of treated lettuce by only sound and only fertilizer was increased 30.88% and 19.61%, respectively, over the control group (both P < 0.0001).

Applied studies of plant meridian system: I. The effect of agri-wave technology on yield and quality of tomato.

Agri-wave technology is a new agricultural technology based on the plant meridian system, that focuses on measurement of plant sound characteristics. The basic principle of agri-wave technology is to improve the yield and quality of plants such as vegetables, flowers, and fruit trees by broadcasting sound waves of certain frequencies and spraying a compound microelement fertilizer on the leaves. The application of agri-wave technology on tomatoes remarkably stimulates growth of their seedlings. Fresh weight of the branch, stems, and leaves of the treated tomatoes is significantly (59.53%, P < 0.0001) higher than that of the control group. Sampling survey results indicate that agri-wave technology accelerates the ripeness of tomatoes. The fresh weight of ripe tomatoes treated with this technique is 30.73% higher than that of the untreated (P = 0.0018), while the fresh weight of the treated unripe tomatoes is 27.29% lower than that of the untreated unripe group (P = 0.0020). Yield surveys show that the yield of treated plants is 13.89% (p < 0.0001) higher than that of the control group. Moreover, with agri-wave technology treatment the storage period of tomatoes is almost doubled. Analysis of tomato nutrition shows that agri-wave technology has increased their sugar content by 26.19%, vitamin A and niacin (an antifavours vitamin) by 55.39% and 92.31% respectively. There is no difference concerning vitamin B1, B2, and D content between the two groups, and vitamin C and E contents decreased by 2.10% and 12.69%, respectively. Among the analyzed 33 minerals of tomatoes, 26 increased in content, while 7 decreased. In conclusion, agri-wave technology has promoted the growth of the tomato, increased its yield, and improved its quality.

Experimental evidence of a plant meridian system: V. Acupuncture effect on circumnutation movements of shoots of Phaselus vulgaris L. pole bean.

When the first unifoliolate leaf of Phaselus vulgaris L. cv. Kentucky wonder pole bean was at the expended stage, two needles were inserted into opposite sides of the stem near the unifoliolate bud and left there for the entire experiment. Changes of the period of circumnutation movement at the shoots of Phaselus vulgaris L. pole bean were measured. Results from two separate experiments are reported in this communication. In the first experiment, the mean period of the ultradian rhythms of the horizontal circumnutation movement of shoots was reduced significantly (p = 0.0022) from 124.2 minutes in controls to 116.3 minutes in the treated plants. The average period of the ultradian rhythms of circumnutation movement in the treated and the untreated groups from the second experiments were 96.7 and 132.1, minutes respectively, which was statistically significant (p < 0.0001). This study demonstrates for the first time that acupuncture markedly shortens the period lengths of the ultradian rhythms of circumnutation movement of the shoots of the Phaselus vulgaris L. pole bean.

Experimental evidence of a plant meridian system: IV. The effects of acupuncture on growth and metabolism of Phaseolus vulgaris L. beans.

We have shown previously that plants exhibit functional characteristics similar to the meridian system in humans and animals, such as high potential and low electrical resistance, high temperature, and spontaneous sound production. Here we will show the effect of acupuncture on plants. When plants of Phaseolus vulgaris L. pole bean (cv. Kentucky wonder) and bush bean (cv. Slenderette) were subjected to acupuncture by inserting two needles into opposite sides of the stem of the unifoliolate buds, it was found that acupuncture strengthened the growth and development of the plants. Two repeated experiments showed that the mean net photosynthesis rate of plants subjected to acupuncture increased about 20.5%, the mean transpiration 27.2%, the growth and total length of internodes 22.5%, and the total dry weight of shoots from the cotyledon to the apex 22.9%, in comparisons with control plants under the same growing conditions. In addition, treated plants flowered three days earlier and had 14.4% more fruit than the untreated control plants. Thus, acupuncture may serve as a viable technique for increasing yield in agricultural plants.

Experimental evidence of a plant meridian system: III. The sound characteristics of phylodendron (Alocasia) and effects of acupuncture on those properties.

Studies on the sound characteristics of phylodendron performed by measuring the power of plant leaves with a laser beam found that the leaves of phylodendron could produce sound waves at relatively low frequencies (from 50 Hz to 120 Hz). Furthermore, it was found that those leaves could accept external sound wave stimulations, with frequencies lower than 150 Hz giving the strongest responses. When the plants were under stress, such as drought, the sound emissions from the plant's leaves increased approximately 20-30 dB, while the range of response to external sound wave stimulation decreased 10-20 dB. However, these increased emissions returned to normal six minutes after watering. When the stainless steel needles were inserted into the petiole of the plant, spontaneous sound production was increased about 40 dB for the main vein and 6 dB for the mesophyll. This is our third report on experimental evidence that plants might have a meridian system as in humans and other animals.

Experimental evidence of a plant meridian system: I. Bioelectricity and acupuncture effects on electrical resistance of the soybean (Glycine max).

Experiments were conducted on the bioelectrical potential and resistance of soybean (Glycine max) roots, stems, leaves and pods. Results showed a higher potential and lower electrical resistance associated with the leaf cushion, main vein and small vein areas in comparison with other parts of the plant. When two needles were inserted into one of the low resistance points, i.e., the leaf cushion area, the electrical resistance decreased 26.0% on the main vein and 4.5% on the mesophyll of the soybean leaf for at least 5 hours after acupuncture. These characteristics, similar to those of meridian transmission lines in humans and other animals, suggest that a meridian system might also exist in plants.

Experimental evidence of a plant meridian system: II. The effects of needle acupuncture on the temperature changes of soybean (Glycine max).

When stainless steel needles were inserted opposite each other in the stem near the unifoliolate buds of soybean plants and retained there for the whole experiment, leaf temperatures increased for two consecutive days. Following acupuncture, the mean temperature of the main vein in the first and second days increased 0.59 degree C and 0.48 degree C, respectively, while the temperature of mesophyll increased only 0.50 degree C and 0.47 degree C in the first and second days. These results are very consistent with studies on the human meridian system. This is our second report on experimental evidence that plants may have a meridian system as is known to exist in mammals.