Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum

Polygonum multiflorum stilbeneglycoside （PMS） is a water-soluble fraction of Polygonum multiflorum Thunb. , one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White （NZW） rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS （25, 50, or 100 mg/kg）. Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule （ICAM）-1 protein and the vascular endothelial growth factor （VEGF） protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.     

Rhodostomin inhibits thrombin-enhanced adhesion of ROS 17/2.8 cells through the blockade of alphavbeta3 integrin.

Osteosarcoma is a very malignant bone tumor which has a high metastatic potential and usually lead to poor prognosis. The adhesion of tumor cells to the endothelium or extracellular matrix (ECM) is an essential step in the metastatic cascade. We investigated the effect of thrombin on the adhesion activity of the osteosarcoma cell line, ROS 17/2.8. Incubation with the low concentrations of thrombin (0.01-5 U/ml, 5 min to 24 h) elevated the adhesion activity of ROS 17/2.8 to both human umbilical vein endothelial cells (HUVEC) and extracellular matrix, with the peak effect at the concentration of 0.5 U/ml for 30 min at 37 degrees C. The ROS 17/2.8 cells responded to thrombin by a peak effect of increased adhesion to HUVEC (5.5 folds vs. control) and fibronectin (4.8 folds) after thrombin pretreatment (0.5 U/ml, 30 min, 37 degrees C). Pretreatment with monoclonal antibodies against beta3 integrins, including anti-alphavbeta3, 10E5 and 7E3, effectively antagonized the thrombin-enhanced cell adhesion activity, whereas anti-alpha3beta1 and anti-alpha5beta1 did not antagonize the enhanced cell adhesion. Rhodostomin, an Arg-Gly-Asp (RGD)-containing snake venom peptide, and synthetic peptide RGDS also blocked the thrombin-enhanced ROS 17/2.8 cell adhesion. This study demonstrated that thrombin enhanced the cell adhesion of ROS 17/2.8 cells to HUVEC or ECM through an upregulation of beta3 integrins, and rhodostomin was a strong inhibitor on thrombin-enhanced cell adhesion, either to HUVEC or fibronectin substratum.     

Paclitaxel decreases the interstitial fluid pressure and improves oxygenation in breast cancers in patients treated with neoadjuvant chemotherapy: clinical implications.

PURPOSE: It has been hypothesized that tumors with high interstitial fluid pressure (IFP) and/or hypoxia respond poorly to chemotherapy (CT) because of poor drug delivery. Preclinical studies have shown that paclitaxel reduces the IFP and improves the oxygenation (pO(2)) of tumors. Our aim is to evaluate the IFP and pO(2) before and after neoadjuvant CT using sequential paclitaxel and doxorubicin in patients with breast cancer tumors of >/= 3 cm. PATIENTS AND METHODS: Patients were randomly assigned, according to an institutional review board-approved phase II protocol, to receive neoadjuvant sequential CT consisting of either four cycles of dose-dense doxorubicin at 60 mg/m(2) every 2 weeks followed by nine cycles of weekly paclitaxel at 80 mg/m(2) (group 1) or vice versa, with paclitaxel administered before doxorubicin (group 2). Patients were re-evaluated clinically and radiologically. The IFP (wick-in-needle technique) and pO(2) (Eppendorf) were measured in tumors at baseline and after completing the administration of the first and second drug. RESULTS: IFP and pO(2) were measured in 54 patients at baseline and after the first CT. Twenty-nine and 25 patients were randomly assigned to groups 1 and 2, respectively. Paclitaxel, when administered first, decreased the mean IFP by 36% (P = .02) and improved the tumor pO(2) by almost 100% (P = .003). In contrast, doxorubicin did not have a significant effect on either parameter. This difference was independent of the tumor size or response measured by ultrasound. CONCLUSION: Paclitaxel significantly decreased the IFP and increased the pO(2), whereas doxorubicin did not cause any significant changes. Tumor physiology could potentially be used to optimize the sequence of neoadjuvant CT in breast cancer.     

Combination bcl-2 antisense and radiation therapy for nasopharyngeal cancer.

PURPOSE: A wide variety of tumors depend on the dysregulation of Bcl-2 family proteins for survival. The resulting apoptotic block can often provide a mechanism for resistance to anticancer treatments, such as chemotherapy and radiation. This current study evaluates the efficacy of combining systemically delivered Bcl-2 phosphorothioate antisense (Bcl-2 ASO) and radiation for nasopharyngeal cancer therapy. RESULTS: Antisense uptake was unaffected by 0, 3, or 6 Gy radiation. Radiation decreased the fraction of viable C666-1 cells to 60%, with a further decrease to 40% in combination with Bcl-2 ASO. Despite a modest in vitro effect, Bcl-2 ASO alone caused the regression of established xenograft tumors in mice, extending survival by 15 days in a C666-1 and by 6 days in a C15 model. The survival times for mice treated with both Bcl-2 ASO and radiation increased by 52 days in C666-1 and by 20 days in C15 tumors. This combination resulted in a more-than-additive effect in C666-1 tumors. Less impressive gains observed in C15 tumors might be attributable to higher expression of antiapoptotic Bcl-2 family proteins and limited drug distribution in the tumor. Retreatment of C666-1 tumors with the Bcl-2 ASO-radiation combination, however, was effective, resulting in mice surviving for >80 days relative to untreated controls. CONCLUSIONS: Our results show that the Bcl-2 ASO and radiation combination is a highly potent therapy for nasopharyngeal cancer. Further examination of combination therapy with radiation and other Bcl-2 family-targeted anticancer agents in both preclinical and clinical settings is definitely warranted.     

Spinal sagittal malalignment following surgery for primary intramedullary tumours in children.

BACKGROUND/OBJECTIVE: As prior studies analysed predictive factors for various post-laminectomy spinal deformities in mixed spinal regions, age groups or pathologies, their validity and conclusions were unclear. The objective of this study was to determine predictive factors for worsened cervical or thoracic spinal sagittal alignment following laminectomy or laminotomy for primary intramedullary spinal cord tumours in children. METHODS: In this retrospective study, patients treated between 1980 and 1998 were reviewed. Changes in spinal alignment at the last follow-up compared to the pre-operative state were studied. Factors analysed were age, pre-operative spinal alignment, procedure types (laminectomy or laminoplasty), number of laminae operated, surgery of C2 or T1 laminae, histological grade, presence of post-operative neurological deficit and post-operative radiotherapy. RESULTS: There were 27 patients. The mean age was 5.6 years (range 1.3-14.0 years), and the mean duration of follow-up was 3.7 years (range 0.075-9.9 years). In the cervical-cervicothoracic surgical group (n = 12), alignment worsened post-operatively in 3 patients. The number of laminae operated upon had a statistically significant impact on the development of post-operative kyphosis (p = 0.07). In the thoracic-thoracolumbar surgical group (n = 15), alignment worsened in 9 patients. Procedure types were statistically significantly different, with laminectomy associated with an increased risk of post-operative kyphosis (p = 0.01). All 5 patients who had spinal fusion for worsened post-operative alignment were in the thoracic-thoracolumbar group; no patients in the cervical-cervicothoracic group required spinal fusion (p = 0.047). Other predictive factors did not reach statistical significance (p > 0.05). CONCLUSIONS: Worsened spinal sagittal alignment following laminectomy or laminoplasty and the need for spinal fusion is more common in the thoracic-thoracolumbar region than in the cervical-cervicothoracic region. In the cervical-cervicothoracic region, operation on a greater number of laminae tends to increase the risk of worsened alignment. In the thoracic-thoracolumbar region, laminectomy is associated with worsened alignment, while laminoplasty reduces this risk; also, pre-operative kyphotic deformity tends to increase the risk of worsened alignment post-operatively.     

Healthy Taiwanese Eating Approach (TEA) toward Total Wellbeing and Healthy Longevity

A healthy dietary pattern review for Asian countries is scarce, which is crucial for guiding healthy eating. We reviewed Taiwanese dietary pattern discovery studies. Included were 19 studies, the majority of which employed dimension reduction methods to find dietary patterns associated with various health conditions. To show what is a high or low intake of foods in Taiwan, we also report the average dietary content and the 25th and 75th percentile values of the adult population for six food groups gathered by the Nutrition and Health Survey in Taiwan, 2017–2020. The healthy Taiwanese dietary approach is cohesive across multiple health outcomes occurring at different ages. It is featured with higher intakes of plant-based foods, aquatic foods, and some beneficial ethnic foods (soy products), drinks (tea), and cooking methods (boiling and steaming); lower intakes of fast foods, fatty and processed meats, sugar, salt rich foods/drinks, and fried foods; but with mixed findings for dairy and egg. Yet, the average Taiwanese person consumed many refined staple foods and livestock, but not sufficient vegetables, fruits, whole grains and roots, beans, and nuts. Dairy consumption remains low. In conclusion, Taiwanese discovery studies point to a mortality-lowering total wellbeing dietary pattern consistent with the current knowledge, which discloses potential benefits of soy product, tea, and boiling and steaming.     

Soybean oil emulsion administration during parenteral nutrition in the preterm infant: effect on essential fatty acid, lipid, and glucose metabolism

To examine the effect of a soybean oil emulsion on essential fatty acid, lipid, and glucose metabolism, preterm infants were randomized to receive 0.5 g/kg/d lipid for 5 days (n = 10, group 1) or 0.5 increased to 2.0 g/kg/d over 5 days (n = 11, group 2). Triene/tetraene ratios did not change in group 1, but decreased in group 2. In both groups, plasma phospholipid linoleate (percent and micrograms per milliliter) increased, the increase being greater in group 2. In both groups, percent content of arachidonate and 5,8,11-eicosatrienoate decreased, and that of oleate remained unchanged. In contrast, absolute content of arachidonate and oleate tended to increase, and that of 5,8,11-eicosatrienoate remained unchanged. At a lipid intake of 0.5 g/kg/d, no infants had hyperlipemia. When lipid intake exceeded 1.0 g/kg/d, the frequency of hypertriglyceridemia (triglycerides greater than 200 mg/dL) and free fatty acidemia, with the free fatty acid/molar albumin ratio exceeding 6:1, increased. Plasma glycerol increased slightly, but was substantially less than the rise in enzymatically determined triglycerides. Hyperglycemia was self-limiting and did not require alteration in dextrose intake. Thus, (1) infusion of a soybean oil emulsion at 0.5 to 2.0 g/kg/d maintains essential fatty acid status and phospholipid arachidonate concentrations; (2) significant hyperlipemia occurs when lipid intake exceeds 1.0 g/kg/d; (3) hyperglycemia associated with lipid infusion tends to be self-limiting and may not require alteration in lipid or dextrose intake; and (4) enzymatically determined triglycerides may be used to monitor lipid tolerance, provided that allowance is made for a small but systematic overestimation resulting from the rise in plasma glycerol.     

Tumor necrosis factor-alpha converting enzyme in the human placenta throughout gestation

Ectodomain shedding of epidermal growth factor receptor ligands such as transforming growth factor- alpha (TGF-alpha), heparin-binding epidermal growth factor-like growth factor (HBEGF), and amphiregulin (AREG) is considered to be important during implantation. Tumor necrosis factor-alpha converting enzyme (TACE) has been suggested as the major sheddase for these molecules. The objectives of this study are (1) to characterize the expression of TACE in the human placenta throughout gestation; (2) to determine the association between the expression of TACE with TGF-alpha, HBEGF, and AREG; (3) to ascertain whether TACE mediates TGF-alpha, HBEGF, and AREG shedding; and (4) to examine the effect of hypoxia on the expression of TACE. By analyzing a total of 55 villous samples representing different gestational ages, the authors found that TACE was continuously expressed in the placentas throughout gestation and that the levels of TACE were positively correlated with the levels of TGF-alpha, HBEGF, and AREG. Preadministration of a TACE inhibitor in villous explant cultures or transfection of cytotrophoblastic cells with TACE-specific small interference RNA decreased the shedding of HBEGF and AREG. Moreover, hypoxia (2% O(2)) caused an increase in the levels of TACE mRNA and protein in villous explants and primary cytotrophoblastic cells in vitro. These results indicate that oxygen regulates the expression of TACE and that TACE may be important for placental development during human pregnancy.     

Abnormally low expression of connexin 37 and connexin 43 in subcutaneously transplanted cryopreserved mouse ovarian tissue

Purpose

To analyze the gap junction proteins connexin 37 (Cx37) and connexin 43 (Cx43) after subcutaneous transplantation of cryopreserved mouse ovarian tissue.

Methods

Expression of gap junction genes was assessed by immunohistochemistry and real-time polymerase chain reaction (PCR) in transplanted cryopreserved ovarian tissue compared with that of normal ovarian tissue. Apoptosis of ovarian cells was evaluated by using the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphates nick end-labeling method.

Results

After subcutaneous transplantation, Cx37 and Cx43 mRNA and protein expression were significantly lower in cryopreserved than in normal ovarian tissue. Apoptosis was increased in granulosa cells from antral follicles of the cryopreserved tissue.

Conclusion

After cryopreservation and subcutaneous transplantation of ovarian tissue, proteins forming gap junctions between oocytes and granulosa cells are under-expressed compared with normal controls.