Analysis on "the essence of tuina, arrival of qi ensuring curative effect" / 中国针灸

In reference with the systematic review of the thought of deqi (arrival of qi) put forward in Huangdi Neijing (Internal Classic of Yellow Emperor) and other classic books of traditional Chinese medicine, in view of detecting qi and identifying qi before treatment, as well as the prerequisites of deqi in tuina, meaning the accurate syndrome differentiation and manipulations, the importance of deqi in treatment with tuina is expounded. In association with clinical experience, the specific manifestations of deqi in patients during tuina are summarized, e.g. soreness, distention, pain, numbness, warm feeling and slight sweating, local changes in intestinal sound and skin color, as well as mind regulation. It is anticipated that deqi of tuina may be drawn the attention in clinical practice, and the relevant study be expanded.

Progress in characteristics and application of olfactory bulbectomy animal model / 药学学报

In rodents, bilateral olfactory bulbectomy (OBX) results in a series of changes in behaviors and neurobiology, similar to the clinical symptoms of depression in patients. These changes can be reversed by chronic but not acute treatment of antidepressants. Owing to the face, construct and predictive validities, the OBX model has been used to investigate the mechanisms of depression, screen for antidepressants, and reveal the mechanism of drug action. In addition, there are certain features in OBX animals resembling those of patients with Alzheimer's disease (AD), including the impaired learning and memory ability and the accumulation of amyloid-β protein (Aβ). In this review, we present the association between olfaction and depression or AD, the surgical procedure of OBX, the behavioral features of OBX animals, the abnormal changes in cortex and hippocampus, and the application of this model for studying depression and AD. These lines of information are important for the development of antidepressant and anti-dementia drugs using this model.

Application of the animal model of intracerebral injection of amyloid-β oligomers to the study of Alzheimer's disease / 药学学报

Progressive accumulation of the amyloid-β peptide (Aβ) in the brain plays a central role in the pathogenesis of Alzheimer's disease (AD). The animal model of intracerebral injection of Aβ oligomers not only provides a method for further exploring the mechanism of Aβ in AD, but also can be used to screen drug candidates targeting Aβ oligomers. This animal model has been widely used in the study of anti-AD drugs and mechanism of AD. In this paper, we summarize the research progress in the animal model of intracerebral injection of soluble Aβ oligomers, including experimental animals, the types of Aβ, the preparation of Aβ oligomers in vitro, injection sites and doses, the duration of modeling, animal behavioral changes, and the pathological mechanisms relating to this animal model, which will contribute to the application of the animal model to various conditions.

Hyperhomocysteinemia and kidney diseases / 生理学报

Homocysteine (Hcy) is an intermediate metabolite of methionine metabolism. Hyperhomocysteinemia (HHcy) is defined as a condition characterized by plasma Hcy level above 16 μmol/L which can result from abnormal Hcy metabolism. HHcy has been confirmed to be related to cardio-cerebrovascular disease, peripheral vascular disorders, neurodegenerative diseases, diabetes, pregnancy-induced hypertension syndrome, liver cirrhosis and kidney diseases. In this review, we summarize the correlation between HHcy and kidney diseases. Elucidating the role of HHcy in kidney diseases may provide a new strategy to prevent and treat kidney diseases.

Jiangtang Xiaozhi Recipe () prevents diabetic retinopathy in streptozotocin-induced diabetic rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the prevention effect of diabetic retinopathy of Jiangtang Xiaozhi Recipe (, JXR) in streptozotocin (STZ)-induced diabetic rats.</p><p><b>METHODS</b>Sprague-Dawley rats were randomly divided into normal control group and diabetic group. Rats in the diabetic group were induced by intraperitoneal administration of STZ (50 mg/kg), and subdivided into 5 groups. Rats in the diabetic control group were given saline; four treatment groups were given metformin (300 mg/kg), JXR (2, 4 and 8 g/kg) respectively for 8 weeks, while rats in the normal control group were injected with citrate buffer and given the same volume of vehicle. Body weight and food intake were measured every week. The hypoglycaemic effects were determined by testing fasting blood glucose (FBG) every other week, and hemoglobin A1c (HbA1c), insulin, and glucagon at the end of the treatment. The preventive effects of JXR on STZ-induced diabetic rats were determined by histopathological examination with hematoxylin and eosin staining, and periodic acid-schiff staining. The effects were further evaluated by serum superoxide dismutase (SOD) activity and malondialdehyde (MDA).</p><p><b>RESULTS</b>High-dose JXR significantly reduced FBG and HbA1c level at the 8th week of administration (P<0.01, P<0.05). JXR significantly increased insulin level (P<0.05), and decreased glucagon level (P<0.05). JXR showed the antioxidant defense with increased SOD activity and decreased MDA contents in diabetic rats. Histopathological studies revealed that there were no basement membrane thickening and mild destruction in the treated groups. Morphometric measurements of retina microvascular showed that acellular capillary and capillary density decreased in treated rats while pericyte and endothelial cell increasing after the treatment.</p><p><b>CONCLUSION</b>JXR have protective effect of diabetic retinopathy and its mechanism may be associated with the obvious hypoglycemic and antioxidant effect.</p>

Anti-tumor effect of suicide gene therapy using chimeric promoter plus radiotherapy on cancer cell lines / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the synergistic anti-tumor effect of radiotherapy and horseradish peroxidase/prodrug indole-3-acetic acid (HRP/IAA) gene therapy system using chimeric hTERT promoter responsive to ionizing radiation.</p><p><b>METHODS</b>The synthetic hTERT promoters containing four tandem-repeat copies of radio-inducible CArG elements, and the chimeric promoter containing cytomegalovirus (CMV) early promoter were both constructed. The activities of the chimeric promoters in cancer cell lines (HeLa, A549, and MHCC97) and normal cell line (MRC-5) were detected using luciferase reporter gene expression analysis after a (60)Co γ-irradiation treatment at a series of doses(a single dose of 0 to 10 Gy). The anti-tumor effect of combining irradiation with HRP/IAA gene-directed enzyme prodrug therapy system controlled by the chimeric promoter was tested by colony formation assay, cell counting and apoptosis analysis.</p><p><b>RESULTS</b>The chimeric promoters were ineffective in normal human cells, even after irradiation, but the expression of luciferase gene in tumor cells was significantly higher. The activity of the chimeric promoter in MRC-5 cells was 22.3%, 12.9% and 13.6% of that in HeLa, A549 and MHCC97 cells, respectively. After irradiation, the ratios were 11.7%, 8.7% and 8.8%, respectively. Furthermore, the chimeric promoters could successfully induce the expression of luciferase gene following different doses of radiation, with maximal inducible activity seen after 6 Gy irradiation. The chimeric promoter containing four tandem-repeat copies of radio-inducible CArG elements and CMV early promoter showed the highest activity with 6 Gy irradiation. The relative luciferase activities in HeLa, A549 and MHCC97 cells were 1.7 ± 0.2, 2.3 ± 0.2 and 2.3 ± 0.1, respectively. The chimeric promoter mediated suicide gene therapy system could increase radio-sensitivity in different cancer cells. Compared with the control system, it plus irradiation showed stronger cell proliferation inhibition, 67.3% vs. 26.1% in HeLa, 69.0% vs. 28.3% in A549, 64.6% vs. 20.8% in MHCC97 cells, and also higher apoptosis-inducing effect, 39.6% vs. 14.2% in HeLa, 33.0% vs. 12.4% in A549, and 33.2% vs. 14.2% in MHCC97 cells.</p><p><b>CONCLUSIONS</b>Chimeric promoter containing hTERT promoter, CArG elements and CMV promoter preserve the tumor-specificity in telomerase-positive tumor cells, and irradiation-responsive to low dose of radiation. The suicide gene therapy using this promoter plus radiotherapy show a strong anti-tumor effect in vitro. It is expected to have a good potential for future application in gene radiotherapy.</p>

CT imaging characteristics of incomplete and complete myocardial bridges-mural coronary artery / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the CT imaging characteristics of incomplete and complete myocardial bridges-mural coronary artery (MB-MCA).</p><p><b>METHODS</b>Fifty subjects with dual source coronary CT angiography (DSCTA) evidenced MB were included. The subjects were divided into incomplete MB-MCA and complete MB-MCA groups. The diameter of MCA in best systole phase and diastole phase, the MCA stenosis rate, the presence of atheromatous change proximal to the MB were evaluated.</p><p><b>RESULTS</b>There were 58 MB, the average length was (2.02 ± 1.02) cm, 23 were incomplete MB and 35 were complete MB. Thirty-two MB were in the middle segments of left anterior descending artery (55.2%); 17 MB were in the distal segment of the left anterior descending artery (29.3%); 1 MB was in the proximal segment of left anterior descending artery; 3 MB in diagonal branch; 4 MB in obtuse marginal branch, 1 MB in distal right coronary artery. It was statistically significant difference between the incomplete MB-MCA and the complete MB-MCA of the diameter change in diastole and systole phase [(1.93 ± 0.49) mm, (1.71 ± 0.45) mm vs. (2.21 ± 0.41) mm, (1.63 ± 0.52) mm, P = 0.008] and stenosis rate (10.38% ± 20.2% vs. 25.12% ± 21.02%, P = 0.01). Atherosclerotic finding was evidenced in 8 incomplete MB (34.78%) and 15 complete MB (42.86%) at the proximal vessel of mural coronary artery (P > 0.05).</p><p><b>CONCLUSION</b>DSCTA can vividly display the incomplete and complete myocardial MB, accurately evaluate the shape change of MB-MCA in diastole and systole phase and detect the atherosclerotic change in the proximal vessel of MB.</p>

Expression of beta-catenin, Glut-1, PTEN proteins in uterine endometrioid adenocarcinoma and its precursor lesions / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the expression of beta-catenin, Glut-1, PTEN in uterine endometrioid adenocarcinoma and their roles in tumorigenesis.</p><p><b>METHODS</b>A total of 83 cases of endometrial hyperplasia were selected and reclassified according to EIN diagnostic criteria. Expressions of beta-catenin, Glut-1 and PTEN proteins were investigated by immunohistochemistry in 10 proliferative endometrium, 83 endometrial hyperplasia and 24 endometrioid adenocarcinoma.</p><p><b>RESULTS</b>(1) 24 EIN (28.9%) lesions were reclassified among 83 previously diagnosed endometrial hyperplasia, of which, 16 of 24 EIN cases (66.7%) had a prior diagnosis of complex atypical hyperplasia. The relation between EIN diagnosis and grade of atypical hyperplasia was not obvious (P > 0.05). (2) Normal (membranous) expression of beta-catenin was present in 10 cases of proliferative endometrium. Abnormal (marked membranous/cytoplasmic, cytoplasmic and/or nuclear or negative) expression rates of beta-catenin in EIN lesions (50%, 12/24) and endometrioid adenocarcinoma (66.7%, 16/24) were significantly higher than that of benign hyperplasia (10.2%, 6/59) respectively (P < 0.01). However, the difference was not significant between EIN lesions and endometrioid adenocarcinomas (P > 0.05). (3) Low level expressions of Glut-1 was present in proliferative endometrium and benign hyperplasia. Overexpression of Glut-1 was present in 58.3% (14/24) of EIN and 70.8% (17/24) of endometrioid adenocarcinoma, respectively, and statistically not significant (P > 0.05). (4) Percentages of loss of PTEN expression showed no difference between EIN lesions (37.5%, 9/24) and proliferative endometrium (2/10), benign hyperplasia (28.8%, 17/59), endometrioid adenocarcinoma (62.5%, 15/24; P > 0.05). However, loss of PTEN expression in endometrioid adenocarcinoma was significantly higher than those in proliferative endometrium and benign hyperplasia (P < 0.05).</p><p><b>CONCLUSIONS</b>Abnormal expression of beta-catenin and overexpression of Glut-1 may be the early events in tumorigenesis of endometrioid adenocarcinoma. The expression of both markers may be useful in distinguishing a benign hyperplasia from EIN and endometrioid adenocarcinoma. Lack of PTEN expression may be the earliest event in endometrial carcinogenesis. However, it can not be used yet as a diagnostic marker for the EIN lesion.</p>

hTERT promoter enhances the radiosensitivity to gene-radiation therapy of human laryngeal carcinoma transplanted in nude mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the therapeutic efficiency of human telomerase reverse transcriptase promoter (hTERTp) mediated horseradish peroxidase (HRP) catalyzed effects of indole-3-acetic (IAA) on laryngeal squamous cell carcinoma with different radiosensitivity in vivo.</p><p><b>METHODS</b>Human laryngeal squamous cell carcinoma Hep-2 and Hep-2R cells were transplanted into nude mice. After growing to about 30 approximately 50 mm3, the tumor-bearing mice were randomly divided into eight groups: Hep-2 line: combined group (A), gene group (B), radiation group (C) and blank group (D); Hep-2R line: combined group (AR), gene group (BR), radiation group (CR) and blank group (DR). The phTERTp-HRP was delivered by intratumoral injection and the IAA by intraperitoneal injection, combined with 2 Gy daily radiation to a total dose of 30 Gy. The tumor volume was recorded. The cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The expression of HRP protein was detected by AP immunohistochemisty.</p><p><b>RESULTS</b>The tumor growth of combined groups was attenuated significantly and the tumor volume of Hep-2R blank group was the largest. The inhibition rate of each group was: A: 54.8%, B: 10.0%, C: 31.9%; AR: 52.7%, BR: 24.8%, CR: 17.0%. In the combined groups, necrosis and apoptosis of tumor cells were observed under the light microscope and the apoptotic index [A (16.6 +/- 1.3)% vs. AR (17.6 +/- 1.3)%] of tumor cells was highest (P < 0.05). The HRP protein expression of BR (33.3 +/- 8.9)% was higher than that of B (21.9 +/- 5.7)%, which was directly up-regulated in the tumors (45.0% vs. 54.8%, P < 0.05) after radiation.</p><p><b>CONCLUSION</b>In the Hep-2- and Hep-2R-transplantation tumors in nude mice, hTERTp can be induced by radiation and enhance the expression of horseradish peroxidase (HRP) gene according to telomerase activity. hTERTp-HRP/IAA system, which has synergistic effects with radiation and inhibits the tumor growth by induction of apoptosis and necrosis, may be a new gene-radiation strategy for the treatment of laryngeal carcinoma.</p>

Effective inhibition of hTERT expression by RNA interference on the radiosensitivity of human laryngeal cancer Hep-2 cell line / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To construct an eukaryotic expression vector of human telomerase reverse transcriptase (hTERT) gene specific shRNA, and investigate the effect of pshRNA-hTERT combined with gamma-irradiation on cell survival and telomerase activity.</p><p><b>METHODS</b>According to the coding sequence of hTERT mRNA, the target of RNAi was designed, and recombinant expression plasmid pshRNA-hTERT was constructed. The vector was transfected into Hep-2 cells. The radiosensitivity of Hep-2 cells was determined by clonogenic assay. Telomeric repeat amplification protocol (TRAP-PCR-ELISA) was used to observe the telomerase activity in each group. Results Recombinant expression vector pshRNA-hTERT was successfully transfected into Hep-2 cells. The hTERT expression inhibition rate reached 60. 8%. pshRNA-hTERT not only inhibited telomerase activity of Hep-2, but also inhibited the raise of telomerase activity induced by gamma-irradiation. Exposure of Hep-2 cells to pshRNA-hTERT for 24 hrs before irradiation resulted in a decrease in mean surviving fraction of Hep-2 cells compared with cells of group with irradiation alone (67. 7% vs 85. 7%, P <0. 05) .</p><p><b>CONCLUSION</b>RNAi showed a significant inhibitory effect to the expression of hTERT. The results indicate that pshRNA-hTERT can effectively inhibit telomerase activity of Hep-2 cells treated or untreated with 2 Gy gamma-irradiation and significantly enhance the radiosensitivity of Hep-2 cells in vitro. The role of radiosensitization of pshRNA-hTERT may be related with the inhibition of telomerase activity.</p>

Protection of Angelica sinensis against radiation-induced pulmonary fibrosis in mice / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the Angelica Sinensis as a protecting agent affecting the radiation-induced pulmonary fibrosis in an animal model,</p><p><b>METHODS</b>The thoraces of C57BL/6 mice were exposed to either sham irradiation or single fraction of 12 Gy. Four groups were defined: that received neither irradiation nor Angelica Sinensis (N group), that received Angelica Sinensis but no irradiation (A group), that underwent irradiation without Angelica Sinensis (NX group) and that received both Angelica Sinensis and irradiation (AX group). Mice were sacrificed at 1, 24, 72 hours and 1, 2, 4, 8, 16, 24 weeks post-irradiation. The lungs tissue were removed and processed for definitive analysis, including hydroxyproline content, HE and Masson staining, and the TGF-beta1, (Transforming Growth Factor beta1, TGF-beta1) mRNA expressions.</p><p><b>RESULTS</b>Compared with N and A group, there was some differences in the AX group, but a significant histological and pathologic changes in NX group. Non-irradiated groups (N and A group) exhibited low levels of hydroxyproline (0.775 +/- 0.024) microg/mg and (0.751 +/- 0.034) microg/mg, and there was a significantly elevated level of hydroxyproline in NX group (0.875 +/- 0.009) microg/mg (P < 0.05). AX group (0.782 +/- 0.010) microg/mg was in between the non-irradiated groups (N and A group) and the radiation-only group (NX group), and the difference between AX group and NX group was significant (P < 0.01). The results of real-time quantitative RT-PCR showed that the relative mRNA expressions of cytokine TGF-beta1 in NX group(249.655 +/- 16.320) was significantly higher than that in group A (1.254 +/- 0.061) and N (1.324 +/- 0.057) (P < 0.01), and that in AX group (108.076 +/- 9.870) decreased than that of NX group (P < 0.01).</p><p><b>CONCLUSION</b>An animal model of mice with radiation-induced lung injure was established successfully. This study has demonstrated that Angelica sinensis in Hibits the progress of radiation-induced pulmonary fibrosis, Possibly by down-regulating the expression of the proinflammatory cytokine Tgfb1. These data suggest that Angelica sinensis maybe useful in preventing and/or treating radiation-induced pulmonary fibrosis in the clinic.</p>

Multi-central controlled study on three-part massage therapy for treatment of insomnia of deficiency of both the heart and spleen / 中国针灸

<p><b>OBJECTIVE</b>To make multi-central clinical evaluation for three-part massage therapy for treatment of insomnia of deficiency of both the heart and spleen.</p><p><b>METHODS</b>One hundred and sixty-six cases were randomly divided into a test group (n = 84) and a control group (n = 82). Multi-central, randomized and controlled methods were adopted. The test group were treated by the three-part massage therapy, i. e. acupoints at the head, abdomen and back were massaged, once each day; and the control group by oral administration of Guipi Pills [symbol: see text], 8 pills each time, thrice daily. The treatment was given for 15 consecutive days and then the therapeutic effects were observed.</p><p><b>RESULTS</b>Sixty-seven cases were cured, 11 markedly effective, 3 effective, and 3 ineffective in the test group, and the corresponding figures were 10, 21, 29 and 22 in the control group with a very significant difference between the two groups (P< 0.001). The test group was superior to the control group in improvement for Pittsburgh Sleep Quality Index (PSQI), Sleepless Anxiety Scale (SAS) and Sleepless Depression Scale (SDS) (P < 0.001).</p><p><b>CONCLUSION</b>The three-part massage therapy has definite therapeutic effect on insomnia of deficiency of both the heart and spleen with safety.</p>

Inverse correlation between Snail and E-cadherin expression in carcinoma cell lines and invasive ability in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Malignant transformation of epithelial cell frequently coincides with loss of E-cadherin. Here we study the expression of Snail and E-cadherin and correlate their expression with cell differentiation and in vitro invasion.</p><p><b>METHODS</b>The expression and localization of Snail and E-cadherin were studied by Northern blot and laser confocal microscopy in two normal cell lines (MDCK, NIH 3T3) and six carcinoma cell lines (A431, MCF-7, MDA-MB-453, HepG2, MDA-MB-435s, MDA-MB-231). Boyden chamber assay was done to detect the invasive ability of cells in vitro.</p><p><b>RESULTS</b>Snail mRNA and protein were detected in fibroblasts NIH 3T3 and poorly differentiated carcinoma cell lines HepG2, MDA-MB-435s and MDA-MB-231. On the contrary, E-cadherin mRNA and protein were detected in normal epithelial cell line MDCK and well differentiated carcinoma cell lines A431 and MDA-MB-453. In MCF-7 cells, Snail and E-cadherin expressions were revealed both at mRNA and protein levels. The cells with higher expression of Snail had stronger ability of invasion than those with lower expression of Snail.</p><p><b>CONCLUSION</b>There is an inverse correlation between Snail and E-cadherin expressions and their expressions are correlated with cell differentiation and tumor invasiveness.</p>

Study on the relationship between polymorphisms of genes (CYP17, CYP19 and SULT1A1) and susceptibility to breast cancer in Chinese women / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between polymorphisms of genes (CYP17, CYP19 and SULT1A1) involved in estrogen metabolism and susceptibility to breast cancer in Chinese women.</p><p><b>METHODS</b>A case-control study was performed. PCR-base restriction fragment length polymorphism (PCR-RFLP) and short tandem repeat polymorphism (STRP) assays were used to detect the polymorphism distribution of CYP17, CYP19 and SULT1A1 in 213 breast cancer cases and 430 matched controls. Logistic regression analyses were used to determine the OR, multivariate adjusted OR and 95% CI of each and all three genes and estrogen exposure factors on the risk of breast cancer. Relationship between polymorphisms and clinic-pathological features was also assessed.</p><p><b>RESULTS</b>The frequency of A2 allele of CYP17 was 49.8% in cases and 49.1% in controls (P > 0.05). The frequency His allele of SULT1A1 in cases (13.6%) was significant higher than that of controls (9.5%) (P = 0.03). There was also significant difference in the frequencies of (TTTA)10 allele CYP19 which was 12.4% in cases and 8.2% in controls (P = 0.02). Multigenic model indicated that there was an increased risk of breast cancer with more numbers of high-risk genotypes in a dose-response effect (trend P = 0.05). Data from multivariate analysis showed that the allele of SULT1A1 His and CYP19 (TTTA)10 was positively associated with the risk of breast cancer. Other well-established risk factors as higher estrogen exposure including total years of menstrual, early menarche etc, and women with a higher BMI and WHR were all served as independent risks.</p><p><b>CONCLUSION</b>This study indicated that the polymorphisms of estrogen-metabolizing genes were related to breast cancer.</p>

Apoptosis induced by short hairpin RNA-mediated STAT6 gene silencing in human colon cancer cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The relationship between signal transduction and tumors has become one of the foci in cancer research. Signal transducer and activator of the transcription 6 (STAT6) signaling pathway is found to be activated in some cancer cells. But the function of the pathway in cancer cells is unknown. This study was undertaken to investigate the effect of the Stat6 signaling pathway on apoptosis in human colon cancer cells (HT-29 cells) and the possible mechanism of Stat6 by RNA interference techniques.</p><p><b>METHODS</b>Four eukaryotic expression plasmid vectors of short hairpin RNA (shRNA) specific for the STAT6 gene were designed and generated by molecular biological technology. The plasmid vectors were transfected into HT-29 cells by cation liposomes to block the Stat6 signaling pathway. The expressions of STAT6 mRNA and phosph-Stat6 protein were detected by the reverse transcriptase polymerase chain reaction (RT-PCR) method and flow cytometry respectively to screen the most effective shRNA at 72 hours after transfection. The apoptosis condition of the cells in which the expression of the STAT6 gene had been interfered was analyzed by flow cytometry and confocal microscopy. Both mRNA and protein expression of B cell lymphoma-2 (Bcl-2) and Bax were detected by RT-PCR and western blotting.</p><p><b>RESULTS</b>Two effective eukaryotic expression plasmid vectors of shRNA specific for the STAT6 gene were generated successfully. One can reduce the expression of the STAT6 gene by 82.4% and the other by 56.8% (P < 0.01). The apoptotic rate of colon cancer cells in which STAT6 gene expression had been interfered was significantly higher than that in controlled colon cancer cells (P < 0.01). In the cells in which the Stat6 signaling pathway was blocked, the levels of mRNA and protein Bcl-2 were significantly decreased, whereas those of Bax were significantly increased (P < 0.01).</p><p><b>CONCLUSIONS</b>The Stat6 signaling pathway can inhibit apoptosis in human colon cancer cells. The subsequent disorder of Bcl-2/Bax expression may play an important part in that process. The STAT6 gene may serve as a potential target in cancer therapy.</p>

Mechanism of improving effect of losartan on insulin sensitivity of non-insulin-dependent diabetes mellitus rats / 生理学报

The specific inhibition of angiotensin II action at AT(1) receptors by losartan has been shown to decrease peripheral insulin resistance in type 2 diabetic patients and animal models. We examined the effect of losartan on the expression of insulin receptor substrate 1 (IRS-1), protein kinase B (PKB) and glucose transporter 4 (GLUT4), as well as the phosphorylation status of IRS-1 and the association between IRS-1 and phosphatidylinositol (PI) 3-kinase in skeletal muscle from fat-fed and-streptozotocin (STZ)-treated rats, an animal model of type 2 diabetes mellitus. In addition, the effects of losartan on GLUT4 translocation in muscle cells and on insulin sensitivity were also evaluated. Muscle tissues were isolated from male losartan-treated and untreated normal or non-insulin-dependent diabetes mellitus (NIDDM) rats with a dose of 4 mg/kg per day for 6 weeks. Oral administration of losartan improved insulin sensitivity, which was determined by an oral glucose tolerance test (OGTT). In skeletal muscles, the protein levels of IRS-1, PKB and GLUT4 in NIDDM rats were not significantly different from those of the control rats, and they were not affected by losartan. The levels of IRS-1 tyrosine phosphorylation, PI 3-kinase activity associated with IRS-1 and PKB activation after stimulation with insulin in muscle tissue of NIDDM rats were significantly decreased (P<0.01) compared with those in the control rats, while they were not increased by losartan. Losartan had a major effect on GLUT4 translocation in myocytes, as it significantly increased (P<0.05) the insulin-induced amounts of GLUT4 in plasma membrane (PM) and T-tubules (TT) in myocytes from NIDDM rats. Consistent with these results, the plasma glucose level in losartan-treated NIDDM rats was decreased (P<0.05) compared with that in untreated NIDDM rats. Our results suggest that losartan may exert beneficial effects on insulin resistance by increasing the translocation of GLUT4 in muscle tissue, which is probably associated with a non-PI 3-kinase-dependent mechanism.

Inhibitory effect of telomerase inhibitors combined with X-irradiation on bone marrow hematopoiesis in mice / 中国实验血液学杂志

The purpose of this study was to evaluate the effect of telomerase inhibitors combined with X-irradiation on bone marrow hematopoiesis in tumor-carrying mice. With an orthogonal experiment design, the telomerase inhibitors [azidothymidine, AZT 300 mg/(kg.day) and lamivudine 150 mg/(kg x day), per os, bid, x 2 weeks] and X-irradiation [total dose 10 Gy (2 Gy x 5) in 1 week] were used to treat BALB/c mice carrying breast cancer MA(782) for evaluating the influence on peripheral blood cells, bone marrow nucleated cells and telomerase activity. Telomerase activity was detected by a PCR-based telomeric repeat amplification protocol (TRAP) coupled with ELISA. The results showed that the number of marrow nucleated cells (x 10(7)/femur) was 2.1875 in untreated group, and 1.7375, 1.7500 and 1.3475 in irradiated, lamivudine and AZT groups, respectively, these suggested that AZT and irradiation could obviously decrease the number of marrow nucleated cells (P< 0.01 or P < 0.05). The peripheral WBC increased 3.7% in untreated mice, and irradiation, lamivudine and AZT reduced 18.09%, 16.19% and 41.00% of WBC, respectively (P < 0.05). Irradiation, lamivudine and AZT showed no obvious effect on RBC and platelet counts (P > 0.05). The telomerase activity (A(450) nm) of marrow cells was 1.498, 1.483, 0.816 and 0.727 in untreated, irradiation, lamivudine and AZT groups, respectively. It is concluded that AZT and lamivudine combined with X-irradiation inhibit bone marrow nucleate cells and the peripheral WBC, manifest inhibitory effect on telomerase activity in murine bone marrow, but have no effect on the peripheral RBC and platelet.