Effects of vibration on the expression of mitochondrial fusion and fission genes and ultrastructure of skeletal muscle in rabbits / 中华劳动卫生职业病杂志

Objective: To study the effects of vibration on the expression of mitochondrial fusion and fission genes and ultrastructure of skeletal muscle in rabbits. Methods: Thirty-two 3.5-month-old New Zealand rabbits were randomly divided into low-intensity group, medium-intensity group, high-intensity group and control group, with 8 rabbits in each group. The rabbits in the experimental group were subjected to hind limb vibration load test for 45 days. The vibration intensity of the high intensity group was 12.26 m/s(2), the medium intensity group was 6.13 m/s(2), and the low intensity group was 3.02 m/s(2) according to the effective value of weighted acceleration[a(hw (4))] for 4 hours of equal energy frequency. The control group was exposed to noise only in the same experimental environment as the medium-intensity group. The noise levels of each group were measured during the vibration load experiment. After the test, the mRNA expression of mitochondrial fusion gene (Mfn1/Mfn2) and fission gene (Fis1, Drp1) by RT-PCR in the skeletal muscles were measured and the ultrastructure of the skeletal muscles were observed in high intensity group. Results: The mRNA expression of mitochondrial in the skeletal muscle tissues of control group, low intensity group, medium intensity group and high intensity group were Mfn1: 3.25±1.36, 3.85±1.90, 4.53±2.31 and 11.63±7.68; Mfn2: 0.68±0.25, 1.02±0.40, 0.94±0.33 and 1.40±0.45; Fis1: 1.05±0.62, 1.15±0.59, 1.53±1.06 and 2.46±1.51 and Drp1: 3.72±1.76, 2.91±1.63, 3.27±2.01 and 4.21±2.46, respectively. Compared with the control group, the expressions of Mfn1 mRNA, Mfn2 mRNA and Fis1 mRNA in the high-intensity group increased significantly (P<0.05) , and the expressions of Mfn2 mRNA in the medium-intensity group and the low-intensity group increased significantly (P<0.05) . Compared with the control group, the ultrastructure of skeletal muscle of high intensity group showed mitochondrial focal accumulation, cristae membrane damage, vacuole-like changes; Z-line irregularity of muscle fibers, and deficiency of sarcomere. Conclusion: Vibration must be lead to the abnormal mitochondrial morphology and structure and the disorder of energy metabolism due to the expression imbalance of mitochondrial fusion and fission genes in skeletal muscles of rabbits, which may be an important target of vibration-induced skeletal muscle injury.

Long-term efficacy of temozolomide in patients with glioblastoma / 中华神经医学杂志

Objective To determine the efficacy of temozolomide (TMZ) in treating patients with glioblastoma using carmustine (BCNU) as control, and examine the effect of O6-methylguanine-DNA methyltransferase (MGMT) expression on the prognosis of patients with glioblastoma. Methods Two hundred and eighty-three patients with pathologically confirmed glioblastoma,admitted to and received treatment without chemotherapeutics in our hospital from January 2004 to January 2009, were enrolled in our study; TMZ was used in 97 patients and BCNU in 186 patients.The glioma tissues were examined for MGMT protein expression by immunohistochemistry.All patients in these 2 groups were performed long-term follow-up for survival time of the patients, tumor response and drug safety. Results In patients of the TMZ treatment group,the median survival time was (19.2±0.6) months,the 2-year survival rate 31％ (30/97),the 5-year survival rate 6.2％ (6/97) and the objective response rate 75.26％ (73/97); while in patients of the BCNU treatment group,the median survival time of was (15.6±0.6) months,the 2-year survival rate 14％ (26/186),the 5-year survival rate 0.5％ (1/186),and objective response rate 45.16％ (84/186); the cumulative survival rate of patients received TMZ treatment was significantly higher than that of patients received BCNU treatment (P＜0.05);the objective response rate between the 2 groups was obviously different (x2=24.753, P=0.000); the incidence of hypoleukocytosis in patients received TMZ treatment was significantly lower than that in patients received BCNU treatment (x2=15.681,P=0.000). Conclusion TMZ shows more efficient oobjective response as compared with BCNU, with less adverse reaction and better tolerability.Therefore,it is an ideal drug of postoperative adjuvant chemotherapy for malignant glioma.

Inducement of U251 glioblastoma cell apoptosis in vivo through up-regulating PUMA expresion and knocking down miR-221/222 / 中华神经医学杂志

Objective To study the inducement of U251 glioblastoma cell apoptosis in vivo through up-regulating PUMA expresion and knocking down miR-221/222, and explore its mechanism.Methods Nude mouse xenograft models were established in 5-week-old BALB/c nude mice by subcutaneous vaccination of U251 glioblastomas; 1 week later, they were treated with intratumoral injection of lipofcctamine-mediated miRNA-221/222 antisense oligonucleotides (GroupA), nonsense sequences (Group B) and controls (Group C),respectively (n=8).The tumor growth was monitored until the end of observation period (28 d after the treatment) and pathological changes of the glioblastoma tissues were observed by HE staining at the end of observation.Fluorescence in situ hybridization (FISH) and real-time PCR were employed to measure the miR-221 and miR-222 expressions. Terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL) assay was used to detect the apoptosis of glioblastomas.Immunohistochemistry and Westem blotting were used to detect the expressions of PUMA,bax,bcl-2 and p53 in removed tumor specimens. Results The volume in Group A was significantly smaller than that of those in group B and group C 6-28 dater treatment (P=0.006). The miR-221 and miR-222 mRNA expressions in Group A were significantly decreased as compared with those of those in group B and group C.HE staining indicated that decreased heteromorphism and reduced number of new vessels in Group A were noted as compared with those in group B and group C.The cell apoptotic index in Group A was significantly higher than that in group B and group C (P＜0.05).Immunohistochemistry showed that the expression levels of PUMA and bax in Group A was significantly up-regulated as compared with those in group B and group C, while the expression of bcl-2 in Group A was significantly down-regulated as compared with that in group B and group C; and no significant changes were noted in the p53 expression. Conclusion By up-regulating PUMA expresion,knocking down miR-221/222 can induce U251 glioma apoptosis in vivo.

Experimental study on combined effect of low temperature and vibration on peripheral circulation function and peripheral nerve function / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the combined effect of low temperature and vibration on function of peripheral circulation and nerve.</p><p><b>METHODS</b>64 rabbits were divided into control group, low temperature group, vibration group and combined effect group randomly, 16 each group. The changes of concentration of ET, Ang II, NO in plasma and SCV, amplitude of sensory nerve action potential, latency of sensory nerve action potential, MCV, distal amplitude of motor nerve, and distal latency of motor nerve were measured before and after experiment.</p><p><b>RESULTS</b>After experiment, the concentration of ET, Ang II, NO and SCV, amplitude of sensory nerve action potential, latency of sensory nerve action potential, MCV, distal amplitude of motor nerve, and distal latency of motor nerve were (68.84+/-14.81) pg/ml, (544.01+/-70.20) pg/ml, (123.73+/-9.58) nmol/ml, (25.36+/-6.96) m/s, (1.84+/-0.65) microV, (4.05+/-1.04) m/s, (27.40+/-6.05) m/s, (1.60+/-0.52) microV, (3.51+/-1.30) m/s respectively in low temperature group; (70.22+/-15.02) pg/ml, (540.77+/-68.25) pg/ml, (129.46+/-11.99) nmol/ml, (27.69+/-6.16) m/s, (2.19+/-0.53) microV, (3.86+/-0.89) m/s, (30.03+/-5.21) m/s, (1.65+/-0.49) microV, (3.36+/-l.11) m/s respectively in vibration group; (88.47+/-13.20) pg/ml, (687.38+/-101.44) pg/ml, (70.66+/-4.99) nmol/ml, (20.82+/-3.65) m/s, (1.21+/-0.64) microV, (5.05+/-0.94) m/s, (19.97+/-4.37) m/s, (1.09+/-0.49) microV, (4.49+/-1.26) m/s respectively in combined effect group; compared with pre-experiment, the concentration of ET and Ang II in low temperature group, vibration group and combined effect group were increased after experiment, and the NO was decreased (P<0.05); the nerve conduct velocity and amplitude was decreased and the latency was delayed (P<0.05). After experiment, the concentrations of ET and Ang II in combined effect group were higher than low temperature group and vibration group, and the concentration of NO in combined effect group was lower than low temperature group and vibration group (P<0.05). After experiment, the SCV and MCV in combined effect group were slower than low temperature group and vibration group; the amplitude of sensory nerve action potential and distal amplitude of motor nerve were less than low temperature group and vibration group; the latency of sensory nerve action potential and distal latency of motor nerve in combined effect group was longer than low temperature group and vibration group. The factorial analysis results indicated the synergistic effect between low temperature and vibration (P<0.05).</p><p><b>CONCLUSION</b>Vibration-induced peripheral vascular impairment and nerve impairment would be intensified by low temperature.</p>

Effects of low temperature on functions of learning, memory and activities of ATPase in brain tissue of mice / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the effects of low temperature on the functions of learning and memory and activities of ATPase in brain tissue of mice.</p><p><b>METHODS</b>120 mice were randomly divided into 3 groups of A, B, and C with different cold exposure time. After low temperature test, learning and memory ability and activities of ATPase in brain tissue of the mice were measured.</p><p><b>RESULTS</b>Compared with corresponding control group, in the test of learning ability, the total electric shock period [(41.00 +/- 12.06), (45.90 +/- 13.61) min], the total electric times (85.00 +/- 15.81, 89.00 +/- 17.29), and the error reaction times (33.60 +/- 10.69, 39.00 +/- 11.63) were increased in group A and group C significantly (P < 0.01, P < 0.05), but the rate of right reaction (53.60% +/- 11.23%, 54.59% +/- 6.14%) were decreased in group A and group C significantly (P < 0.01, P < 0.05). In the test of memory ability, the total electric shock period [(19.00 +/- 4.62), (51.70 +/- 15.19) min] in group A and group C were increased significantly (P < 0.05, P < 0.01), the rate of right reaction (86.17% +/- 6.34%, 65.92% +/- 8.17%) in group A and group C were decreased significantly (P < 0.05). In test of activities of ATPase in brain tissue, the activities of Na(+)-K(+)-ATPase and activities of Ca(2+)-Mg(2+)-ATPase in brain tissue in group A and group C were decreased significantly (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>Low temperature could decrease the functions of learning and memory and the activities of Na+-K+-ATPase and Ca(2+)-Mg(2+)-ATPase in brain tissue of mice.</p>

Inhibitory effect of knocking down microRNA-221 and microRNA-222 on glioma cell growth in vitro and in vivo / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the inhibitory effect of knocking down microRNA(miR)-221 and miR-222 on human glioma cell growth and its possible mechanism.</p><p><b>METHODS</b>miRNA-221/222 antisense oligonucleotides (antisense miR221/222) were transfected into human glioma U251 cells by lipofectamine. Northern blot analysis was conducted to detect the mRNA expression of miR-221/222 in the control and transfected cell groups. The proliferation activity of cells was determined by MTT assay. Cell invasion ability was examined by transwell assay, and cell cycle kinetics and apoptosis were detected with flow cytometry. The expression of relevant proteins was analyzed by Western blotting. The therapeutic efficacy of antisense miR221/222 on the growth of xenograft tumors in nude mice were also observed.</p><p><b>RESULTS</b>In the antisense miR-221/222-transfected cells, the expression of miR-221/222 was significantly reduced; the cell invasion ability was suppressed, cell cycle was blocked at G(0)/G(1) phase, and apoptotic cells were increased. The growth of xenograft tumors treated with antisense miR-221/222 was also inhibited. In antisense miR-221/222 treated tumor cells, the expression of bcl-2 was down-regulated while connexin43, p27, PUMA, caspase-3, PTEN, TIMP3 and Bax up-regulated, and p53 expression not changed.</p><p><b>CONCLUSION</b>There is a significant inhibitory effect of antisense miR-221/222 on the growth of human glioma U251 cells. miR-221/222 may be considered as a candidate target for gene therapy of human gliomas.</p>

Effect of captopril on the nervous function in rabbits exposed to vibration / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the effect of captopril on the nervous function in rabbits exposed to vibration.</p><p><b>METHODS</b>Rabbits were divided into vibration group, intervention group, and control group. Vibration group and intervention group were exposed to (tested by) vibration. Captopril was given to intervention group from the 11th day of vibration exposure. Somatosensory evoked potential (SEP) and motor nervous conduction function (MCF) were measured and analyzed in each group before and after vibration exposure.</p><p><b>RESULTS</b>The latent periods of N1, P1 and N2 of SEP in vibration group after vibration exposure were (30.76 +/- 4.26), (41.91 +/- 6.67), and (45.29 +/- 5.81) ms respectively, and in intervention group after vibration exposure were (27.00 +/- 3.04), (35.07 +/- 4.20) and (41.15 +/- 3.19) ms respectively. Compared with intervention group before and after exposure, and control group, the latent periods of each wave of SEP were delayed significantly (P < 0.05). The nervous conduction velocity, the distant wave amplitude, and the distant potential period of sciatic nerve in vibration group after vibration exposure were significantly different from those in intervention group [(35.69 +/- 4.37) m/s, (1.55 +/- 0.73) microV, (8.16 +/- 0.71) ms respectively vs (52.20 +/- 5.13) m/s, (2.89 +/- 0.36) microV, (7.26 +/- 0.77) ms respectively (P < 0.01)].</p><p><b>CONCLUSION</b>Captopril may improve the impairment of nervous functions to a certain degree in rabbits exposed to vibration.</p>