白花蛇舌草-半枝莲药对组分对结肠腺癌Lovo细胞生物学行为的影响

摘要:目的　探讨白花蛇舌草-半枝莲药对组分对结肠腺癌Lovo细胞增殖、侵袭、迁移和凋亡的影响及作用机制。方法　将白花蛇舌草、半枝莲按质量1∶1进行3次煎煮,获得水提物,后取适量浸膏用石油醚回流脱脂,再以乙酸乙酯进行多次萃取,获得白花蛇舌草-半枝莲药对组分,并计算得率。实验分为对照组（正常培养Lovo细胞）、白花蛇舌草-半枝莲药对组分低剂量组（10 mg/L）、中剂量组（30 mg/L）及高剂量组（50 mg/L）。通过噻唑蓝比色法（MTT）检测各组细胞培养24、48、72 h后的增殖抑制率。各组细胞培养48 h后,流式细胞仪检测细胞周期分布;Transwell实验检测细胞侵袭能力;划痕实验检测细胞迁移能力;TUNEL法检测细胞凋亡情况;Western blot法检测Grb2相关结合蛋白1（Gab1）、血管内皮生长因子受体2（VEGFR-2）、磷脂酰肌醇3-激酶（PI3K）、苏氨酸激酶（Akt）、基质金属蛋白酶-9（MMP-9）、B淋巴细胞瘤-2基因（Bcl-2）、Bcl-2相关X蛋白（Bax）蛋白表达情况。结果　化学萃取后的白花蛇舌草-半枝莲药对中主要含有对羟基苯乙酮、野黄芩苷、木犀草素和芹菜素4种化合物,组分得率为0.61%。与对照组相比,低、中、高剂量组细胞增殖抑制率升高,G1期肿瘤细胞比例增加,细胞凋亡指数增高,侵袭细胞数和划痕闭合率明显减小（均P＜0.05）,细胞中Gab1、VEGFR-2、PI3K、Akt、MMP-9、Bcl-2蛋白表达降低,Bax表达升高（均P＜0.05）,且存在剂量依赖性。结论　白花蛇舌草-半枝莲药对组分可抑制结肠腺癌Lovo细胞的增殖,降低其迁移和侵袭能力,诱导细胞凋亡,其机制可能与抑制Gab1/VEGFR-2/PI3K/Akt信号通路活化有关。     

Toxicity of fungicides to Pisum sativum: a study of oxidative damage,growth suppression,cellular death and morpho-anatomical changes

Considering the fungicidal threat to the sustainable agro-environment, the toxicological impacts of three fungicides, namely kitazin, hexaconazole and carbendazim, on the biological, chemical and morpho-anatomical changes of peas were assessed. Fungicide applications in general caused a slow but gradual reduction in growth, symbiosis and yields of peas, which, however, varied appreciably among species and concentrations of the three fungicides. Of the three fungicides, carbendazim had the most lethal effect, in which it delayed seed germination and also diminished the overall pea growth. Carbendazim at 3000 μg kg⁻¹ maximally reduced the germination, SVI, size of roots and shoots and total dry matter accumulation in roots, shoots and whole plants distinctly by 40%, 84%, 72%, 73%, 68%, 75% and 73% (p ≤ 0.05), respectively. Hexaconazole at 120 μg kg⁻¹ significantly (p ≤ 0.05) declined total chlorophyll, carotenoids, grain yields, grain protein, root P and shoot N by 19%, 28%, 46%, 69%, 48% and 51%, respectively, over the control. The synthesis of stress biomarkers and oxidative stress were increased with increasing dosage rates of fungicides. Proline content in roots, shoots, leaves and grains, MDA, electrolyte leakage and H₂O₂ of plants grown in soil treated with 288 μg kg⁻¹ kitazin were increased significantly (p ≤ 0.05) by 73%, 52%, 41%, 24%, 59%, 40% and 27%, respectively, relative to the control. Antioxidant defence enzymes were greater in pea foliage. The SEM and CLSM images revealed an obvious alteration in root tips, enhanced cellular damage and cell death when plants were raised under fungicide stress. Also, morpho-anatomical variations in fungicide-treated foliage were visible in the SEM images. Overall, the present study suggests that a careful and secure strategy should be adopted before fungicides are chosen for enhancing pulse production in different agro-climatic regions.

Considering the fungicidal threat to the sustainable agro-environment, the toxicological impacts of three fungicides, namely kitazin, hexaconazole and carbendazim, on the biological, chemical and morpho-anatomical changes of peas were assessed.     

Granulocyte-macrophage colony-stimulating factor augmentation of T-cell receptor-dependent and T-cell receptor-independent thymocyte proliferation

The effects of granulocyte-macrophage colony-stimulating factor (GM- CSF) are not confined to cells of the myeloid lineage. GM-CSF has been shown to have effects on mature T cells and both mature and immature T- cell lines. We therefore examined the GM-CSF responsiveness of murine thymocytes to investigate whether GM-CSF also affected normal immature T lymphocytes. The studies presented here indicate that GM-CSF augments accessory cell (AC)-dependent T-cell receptor (TCR)-mediated proliferation of unseparated thymocyte populations. To identify the GM- CSF responsive cell type, thymic AC and T cells were examined for GM- CSF responsiveness. We found that GM-CSF augmentation of TCR-induced thymocyte proliferation appears to be mediated via augmentation of AC function, and not via direct effects on mature single-positive (SP) thymocytes. Enriched double-negative (DN) thymocytes were also tested for GM-CSF responsiveness. GM-CSF induced the proliferation of adult and fetal DN thymocytes in an AC-independent and TCR-independent single- cell assay. Thus, in contrast to the SP thymocytes, a DN thymocyte population was directly responsive to GM-CSF. GM-CSF therefore may play a direct role in the expansion of DN thymocytes and an indirect role in the expansion of SP thymocytes.     

Results of ACDF using Alexandria Modular Cage-Plate Construct in cervical canal stenosis

Background

The purpose of this study was to assess prospectively operative results and complications of treatment of cervical spinal canal stenosis (CCS) by anterior cervical discectomy and fusion (ACDF) using a newly introduced Alexandria Modular Cage-Plate Construct (AMCPC).

Methods

Fifteen patients (eight males, seven females) with symptomatic CCS were treated by ACDF, with a mean age of 51.2 years. Post-operative assessment depended upon clinical and radiological results.

Results

Total number of operated levels was 25 levels, with a mean 1.67 levels/patient. Mean operative time was 69.6 min/level and 116 min/patient. Average blood loss was 78 mL/level and 130 mL/patient. Mean hospital stay was 2.8 days. Post-operative dysphagia/dysphonia persisted in one patient for 1 year. One patient developed C5 radiculopathy with grade 2 deltoid weakness that recovered after 3 months. According to Odom’s criteria, results were excellent in 13 patients (86.67 %), good in 1 (6.67 %), and fair in 1 patient. In 13 patients (23 cage-plates, 92 %), the implant showed to be completely contained until the end of follow-up (24 months). One patient had a broken screw and one had screw backing-out, both did not necessitate revision. The achieved sagittal profile was maintained without sinking-in of any cage.

Conclusion

AMCPC can be used safely for a variety of disorders requiring instrumentation and fusion. It is advantageous to stand-alone cage and to rigid cage-plates when intraoperative flexibility is needed. It overcomes the disadvantages of stand-alone cage, sinking-in, cage dislodgement and post-operative rekyphosis. In addition, it obviates the need for wearing post-operative neck collar.     

The use of bisphosphonates in children: review of the literature and guidelines for dental management

Bisphosphonates are inhibitors of osteoclastic bone resorption with therapeutic benefit in a variety of bone disorders in both adults and children. While these agents have been routinely used in adults for the past three decades, their more recent introduction into paediatric medicine means there is a paucity of data on long‐term safety and effects on dental development. There is uncertainty regarding the dental management of children treated with bisphosphonates, particularly when invasive dental procedures, such as extractions and oral surgical procedures, are required. There are limited data with which to make recommendations about the dental management of patients treated with bisphosphonates, and there are no published recommendations that specifically address paediatric patients. This paper aims to outline paediatric uses and adverse effects of bisphosphonates and present recommendations on the dental management of children receiving bisphosphonates.     

Erysipelas of the upper extremity following locoregional therapy for breast cancer

Cellulitis is a well-known complication of lymphedema of the lower extremities. Erysipelas of the upper extremity complicating breast cancer therapy has never been reported in the English-language literature. We describe seven breast cancer patients with erysipelas of the upper extremity. Five had a predisposing injury to the extremity. All patients responded very well to intravenous antibiotics without any sequelae. They had rapid resolution with typical desquamation. No long-term sequelae were seen except for mild increase of lymphedema. Erysipelas should be listed as a rare complication after locoregional therapy for breast cancer. Intravenous penicillin should be used as the initial therapy. Prevention of arm lymphedema and avoidance of any trauma to the arm are important prophylactic measures. Sentinel lymph node biopsy reduces the rate of axillary lymph node dissection and thus should reduce the incidence of lymphedema and erysipelas.     

A longitudinal study of otitis media with effusion among 2- to 5-year-old African-American children in child care

OBJECTIVE: To prospectively document the prevalence of otitis media with effusion (OME) in 86 African-American children between ages 2 and 5 years. STUDY DESIGN: Eighty-six children in center-based child care whose ear status had been followed from infancy continued to be observed. Middle ear status was assessed by pneumatic otoscopy and tympanometry biweekly. RESULTS: The prevalence of OME decreased as children became older. The mean proportion of examinations demonstrating bilateral OME (BOME) ranged from 12% between 24 to 30 months to 4% between 54 to 60 months of age. The mean proportion of exams revealing bilateral normal ears increased from 77% at 24 to 30 months to 88% at 54 to 60 months of age. Although 60 children had experienced BOME that lasted 4 months or longer in the 6- to 24-month age period, only 8 of these children experienced at least 4 months of continuous BOME between 24 to 60 months. CONCLUSIONS: The proportion of time with BOME decreased progressively with increasing age in this population. Only 8 of 60 children who had experienced more than 4 consecutive months of BOME before 2 years of age continued to manifest persistent effusion or experience recurrences of prolonged BOME after 2 years of age.     

Comparative efficacy of exenatide versus insulin glargine on glycemic control in type 2 diabetes mellitus patients inadequately treated with metformin monotherapy

PurposeComparative efficacy of exenatide versus insulin glargine primarily on glucemic control, and secondarily on body mass index (BMI), lipid profile and blood pressure, in type 2 diabetes mellitus (T2DM) patients suboptimally treated with metformin monotherapy.Material/MethodsForty-seven inadequately treated T2DM patients on metformin assigned to exenatide (n=18) or insulin glargine (n=29) for 26 weeks. Glycosylated hemoglobin (HbA1c), serum lipids, BMI, systolic and diastolic blood pressure, and adverse events, including episodes of hypoglycemia and gastrointestinal symptoms, were recorded.ResultsEither treatment had a similar favorable mean reduction in HbA1c. However, more patients in exenatide group achieved HbA1c ≤ 7% at the 26th week compared with insulin glargine group (p=0.036). Insulin glargine group had significantly more episodes of hypoglycemia compared with exenatide group (p=0.039). Gastrointestinal adverse events were non-significantly higher in the exenatide group. A significantly greater BMI reduction was observed in exenatide group, whereas BMI was not altered in insulin glargine group. Total and LDL cholesterol (p=0.012), and triglycerides (p=0.016) significantly decreased, whereas HDL cholesterol increased (p=0.021) in the exenatide group, whereas only total cholesterol decreased in insulin glargine group. Changes in systolic and diastolic blood pressure were insignificant in both groups.ConclusionsExenatide provided similar reduction in HbA1c, but fewer episodes of hypoglycemia, compared with insulin glargine. Exenatide had also a favorable effect on weight loss, although more gastrointestinal adverse events. Exenatide may provide a justified alternative in second line treatment of T2DM, but more trials are required to elucidate its long-term safety and cost-effectiveness.