The synergistic effect of palmitic acid and glucose on inducing endoplasmic reticulum stress-associated apoptosis in rat Schwann cells.

OBJECTIVE: Diabetic peripheral neuropathy (DPN) is a common long-term complication of diabetes mellitus accompanied with hyperglycemia and hyperlipidemia. Both high blood glucose and high blood lipids are key pathogenies for DPN. This research aims to investigate whether the combination of glucose (Glu) and palmitic acid (PA) played a synergistic role in the pathogenesis of DPN. MATERIALS AND METHODS: The proliferation rate of Rat Schwann cell line RSC96 cells stimulated by different concentrations of Glu and PA were analyzed by CCK-8 assay. After the IC50 was detected for each drug, the RSC96 cells were divided into control, Glu, Glu+PA, PA, and BSA groups. The apoptosis of RSC96 cells in different groups were detected by flow cytometry. The effects of Glu and/or PA on endoplasmic reticulum (ER) stress-associated apoptotic signaling pathways were determined by Western blot and qPCR. RESULTS: Both Glu and PA showed similar inhibition on the proliferation of RSC96 cells in a dose-dependent manner. However, PA induced stronger apoptosis of RSC96 cells than glucose and significantly increased the levels of X-box-binding protein-1 (XBP1), C/EBP homologous protein (CHOP), and eIF2α phosphorylation, which are key proteins regulating endoplasmic reticulum (ER) stress-associated apoptotic signaling pathways. The combination of Glu and PA induced the strongest apoptosis in RSC96 cells and also activated ER stress-associated apoptotic signaling pathways. These results verified the synergistic effect of Glu and PA on inducing ER stress-associated apoptosis in RSC96 cells, and PA even induced stronger apoptosis in RSC96 cells than Glu. CONCLUSIONS: The present research indicated that hyperglycemia and hyperlipidemia might exert a synergistic damage during the pathogenesis of DPN, suggesting that blood lipid control is as important as blood glucose control for DPN patients.

[Effect of primary lesion resection on the prognosis of patients with advanced breast cancer].

Objective: To explore the effect of the resection of the primary lesion on the prognosis for patients with stage Ⅳ breast cancer. Methods: A total of 132 breast cancer patients who were first diagnosed as stage Ⅳ in the Hebei Cancer Hospital from June 2008 to June 2015 were divided into two groups: the primary resection group (n=85) and the unresection group (n=47). The influences of primary resection, timing of operation, lymph node removal or dissection and radiotherapy on the prognosis of stage Ⅳ breast cancer patients were analyzed. Results: Multivariate Logistic regression analysis showed that visceral metastasis was an independent influencing factor for primary lesion resection in stage Ⅳ breast cancer patients (OR=2.590, 95% CI: 1.090-6.159). Multivariate Cox regression analysis showed that primary resection was an independent factor for the improvement of prognosis in stage Ⅳ breast cancer patients (OR=0.582, 95% CI: 0.400-0.847). The median overall survival (OS) was 37.20 months in the resection group, which was higher than 24.10 months in the unresection group (χ(2)=8.108, P=0.004). Among patients aged ≥50 years old, the median OS was 39.30 months in the resection group and 23.03 months in the unresection group, and the difference was statistically significant (χ(2)=14.191, P<0.001). The median OS was 38.00 months in the 66 patients with the operation time from diagnosis to resection of primary lesion<6 months (n=66), and 35.20 months for ≥6 months (n=19) (χ(2)=4.430, P=0.035), the difference was statistically significant (χ(2)=4.430, P=0.035). The median OR of axillary lymph node dissection and axillary lymph node excision group were 45.37 months and 33.44 months, respectively, the difference was statistically significant (χ(2)=7.832, P=0.005). The median OS of postoperative radiotherapy group and non-radiotherapy group were 44.80 months and 33.20 months, respectively, the difference was not statistically significant (χ(2)=2.950, P=0.086). Conclusion: Resection of the primary lesion may prolong the survival time of some advanced breast cancer patients.

[A multicenter clinical study for the comparison of S-1 versus capecitabine in the treatment of advanced breast cancer].

Objective: To investigate the safety, efficacy and prognostic factors of S-1 versus capecitabine in patients with advanced breast cancer (ABC). Methods: From January 1, 2012 to December 31, 2014, 154 ABC patients with pathological diagnosis were separated into two groups: S-1 with or without the 3rd generation chemotherapy drug (group S-1) and capecitabine with or without the 3rd generation chemotherapy drug (Group capecitabine). The efficacy, side effects and prognostic factors were compared between the two groups. Results: There were 70 patients in group S-1 and 84 patients in group capecitabine. The objective response rates (ORR) were 31.4% (22/70) in group S-1 and 28.6% (24/84) in group capecitabine. The disease control rates (DCR) were 74.3% (52/70) and 83.3% (70/84), respectively. There were no significant differences in DCR and ORR between two groups (P>0.05). The DCR of patients treated with capecitabine monotherapy was significantly higher than that of S-1 monotherapy [94.4%(17/18) and 64.0%(16/25), P=0.028]. The median PFS was 7.5 and 8.9 months for the patients in the group S-1 and group capecitabine, with no statistically significant difference (P=0.423). The 1-year survival rates of group S-1 and group capecitabine were 81.4% and 66.7%, respectively, with no significant differences(P=0.020). Univariate analysis showed that ER and/or PR status (P=0.004), T stage (P=0.041), and molecular typing (P=0.046) were associated with PFS. Multivariate analysis showed ER and/or PR status (P=0.034) was an independent prognostic factor related with PFS. The incidence of hemoglobin reduction was 14.3% (10/70) and 36.9% (31/84) in the group S-1 and group capecitabine, and the differences were statistically significant (P=0.002). There was no significant difference in the incidence of leukopenia, neutropenia, thrombocytopenia and hand-foot syndrome between the two groups(P>0.05). Conclusions: S-1 and capecitabine are both effective for advanced breast cancer. Neither ORR nor DCR were significantly different between these two groups. The incidence of gastrointestinal reactions and thrombocytopenia of S-1 was slightly lower than that of capecitabine.

Expression and clinical significance of obesity-associated gene STEAP4 in obese children.

The aim of this study was to investigate the expression and clinical significance of the obesity-associated gene STEAP4 in obese children. Fifty-three obese children and 33 children with a standard body weight (control) from our hospital were recruited to this study. The expression of STEAP4 mRNA and protein in the adipose tissue were detected by reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay, respectively, in order to analyze the relationship between STEAP4 mRNA and protein levels and blood pressure, blood lipid profile, blood glucose levels, and inflammation in obese children. Obese children showed significantly lower levels of STEAP4 mRNA and protein in the adipose tissue compared to the control subjects (P < 0.05). The obese subjects exhibited significantly higher diastolic blood pressure (DBP), systolic blood pressure (SBP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), fasting plasma glucose (FPG), interleukin (IL)-6, and tumor necrosis factor (TNF)-α levels, and a significantly lower high-density lipoprotein (HDL) level, compared to the control subjects (P < 0.05). Correlation analysis revealed that STEAP4 expression was negatively correlated with the DBP, SBP, TC, TG, LDL, FPG, IL-6, and TNF-α levels, and was positively correlated with the HDL level (P < 0.05). In conclusion, the expression of STEAP4 was significantly downregulated in the adipose tissue of obese children and was closely related to the blood pressure, blood lipid, blood glucose, and inflammation in these patients; therefore, these results could provide a theoretical basis for the treatment of childhood obesity.

Preliminary study on diagnosis of lumbar disc degeneration with magnetic resonance T1p, T2 mapping and DWI quantitative detection technologies.

OBJECTIVE: The value of diagnosing lumbar disc degeneration with T1p magnetic resonance imaging (MRI), T2 mapping and diffusion-weighted imaging (DWI) technologies. PATIENTS AND METHODS: We selected 30 patients diagnosed with lumbar disc herniation (group A), 30 patients with lumbar disc degeneration (group B) and 30 healthy volunteers (group C) and carried out Pfirrmann grading of intervertebral discs (L1-S1 segment) based on conventional T2WI median sagittal images. T1p, T2 mapping and DWI were then applied. RESULTS: Group A primarily had Pfirrmann grades of III-IV, group B had Pfirrmann grades of I-IV and group C had Pfirmann grades of I-II. The differences between the groups were statistically significant (p <0.05). The average T1p, T2 mapping and apparent diffusion coefficient (ADC) values of the nucleus pulposus and annulus fibrosus in group A were significantly lower than in group B. The highest values were in group C, and the differences were statistically significant (p <0.05). CONCLUSIONS: T2WI, T1p MRI, T2 Mapping and DWI technologies have different capacities to diagnose lumbar disc degeneration, and have great value in improving diagnostic accuracy.

Genetic diversity of Broussonetia papyrifera populations in southwest China.

Broussonetia papyrifera is an important native tree species with high economic value in southwest China. Its resources are drastically reduced because of over-harvesting and habitat fragmentation. In this study, 17 natural populations of B. papyrifera were analyzed using inter-simple sequence repeat (ISSR) markers to assess the genetic diversity and population structure. In total, 100 bands were obtained from 16 ISSR primers. The B. papyrifera populations showed relatively high genetic diversity at the species level [percentage of polymorphic bands (PPB): 96%; Nei's genetic diversity (HE): 0.3074; Shannon's information index (I): 0.4617], while the genetic diversity at the population level was relatively low (PPB: 53.2%; HE: 0.1826; I: 0.2735). Relatively high level of genetic differentiation among populations (41%) was disclosed by analysis of molecular variance, which agrees with the Nei's genetic diversity statistics (40.59%) and Shannon's information measure (40.76%). Gene flow among populations (NM) was only 0.7318. A significant correlation was observed between genetic and geographic distance among the studied populations (r=0.2948). We conjectured that the genetic diversity of B. papyrifera resulted from human disturbance, habitat fragmentation, small effective population size, and geographic barrier. Given the high genetic differentiation among populations, some utilization and conservation strategies were proposed. This study provides a reference for the sustainable use of the species in southwest China.

Platelet-derived growth factor receptor kinase inhibitor AG-1295 promotes osteoblast differentiation in MC3T3-E1 cells via the Erk pathway.

Previous studies have conflicting views on the effect of platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR) signaling on osteogenesis. The current study investigated the effect of PDGF receptor-beta (PDGFR-ß) inhibition by AG-1295 on the osteogenic differentiation of the mouse pre-osteoblastic cell line MC3T3-E1. Osteogenic differentiation was induced by treatment with ß-glycerophosphate, ascorbic acid, and dexamethasone along with or absent AG-1295. Results showed that AG-1295 significantly increased alkaline phosphatase (ALP) activity and enhanced the formation of mineralized nodules in a dose-dependent manner. Furthermore, treatment with AG-1295 resulted in up-regulated mRNA expression of the osteogenic marker genes collagen type I (Col1A), runt-related transcription factor 2 (Runx2), osterix (Osx), tissue-nonspecific alkaline phosphatase (Tnap), and osteocalcin (Ocn). Consistent with its effect on osteoblast differentiation, AG-1295 also significantly suppressed the phosphorylation of Erk1/2 in MC3T3-E1 cells. In conclusion, findings suggest that blocking the PDGFR-ß pathway with AG1295 markedly promotes osteoblast differentiation and matrix mineralization in mouse osteoblastic MC3T3-E1 cells and that the Erk1/2 pathway might participate in this process.

Aqueous foams stabilized by in situ surface activation of CaCO3 nanoparticles via adsorption of anionic surfactant.

The in situ surface activation of unmodified CaCO(3) nanoparticles by interaction with surfactant in aqueous media has been studied, and the impact of this on the foamability and foam stability of aqueous dispersions was assessed. Using complementary experiments including measurement of particle zeta potentials, adsorption isotherms of surfactant, air-water surface tensions, and relevant contact angles, the mechanism of this activation was revealed. The results show that the non-surface-active CaCO(3) nanoparticles cannot be surface activated by interaction with cationic or nonionic surfactants but can be surface activated by interaction with anionic surfactants such as SDS and AOT, leading to a synergistic effect in both foamability and foam stability. The electrostatic interaction between the positive charges on particle surfaces and the negative charges of anionic surfactant headgroups results in monolayer adsorption of the surfactant at the particle-water interface and transforms the particles from hydrophilic to partially hydrophobic such that particles become surface active and stabilize bubbles. SDS is a more efficient surfactant for this surface activation than AOT. Possible reasons for this difference are suggested.

Effects of surfactant structure on the phase inversion of emulsions stabilized by mixtures of silica nanoparticles and cationic surfactant.

Silica nanoparticles without any surface modification are not surface active at the toluene-water interface due to their extreme hydrophilicity but can be surface activated in situ by adsorbing cationic surfactant from water. This work investigates the effects of the molecular structure of water-soluble cationic surfactant on the surface activation of the nanoparticles by emulsion characterization, adsorption and zeta potential measurements, dispersion stability experiments, and determination of relevant contact angles. The results show that an adsorbed cationic surfactant monolayer on particle surfaces is responsible for the wettability modification of the particles. In the presence of a trace amount of cationic surfactant, the hydrophobicity of the particles increases, leading to the formation of stable oil-in-water O/W(1) emulsions. At high surfactant concentration (>cmc) the particle surface is retransformed to hydrophilic due to double-layer or hemimicelle formation, and the concentration of the free surfactant in the aqueous phase is high enough to stabilize emulsions alone. O/W(2) emulsions, probably costabilized by free surfactant and particles, are then formed. The monolayer adsorption seems to be charge-site dependent. Thus, using single-chain trimethylammonium bromide surfactants or a double-head gemini cationic surfactant, the hydrophobicity of the particles achieved is not sufficient to stabilize water-in-oil (W/O) emulsions, and no phase inversion is induced. However, using a double-chain cationic surfactant, the chain density on the particle surfaces endows them with a hydrophobicity high enough to stabilize W/O emulsions, and double phase inversion, O/W(1) --> W/O --> O/W(2), can then be achieved by increasing the surfactant concentration.

Optimal protocol for total body irradiation for allogeneic bone marrow transplantation in mice.

We have previously demonstrated, using chimeric resistant MRL/lpr mice, that a fractionated total body irradiation (FTBI) (5 Gy x 2 with a 4 h interval on the day before allogeneic bone marrow transplantation (BMT)) is the best conditioning regimen for the treatment of autoimmune diseases in radiosensitive MRL/lpr mice. In the present study, using various standard strains of mice (not radiosensitive mice), we explore the best protocol for irradiation (doses and intervals) as the conditioning regimen for allogeneic BMT. Recipient mice were exposed to various irradiation regimens: a single total body irradiation (TBI) of 9.5 or 12 Gy and FTBI of (5+5) Gy to (7+7) Gy with a 1 to 24 h interval. The method generally utilized for humans ((2+2) Gy with a 4 h interval for 3 days (total 12 Gy)) was also used. One day after the last irradiation, donor BMCs from BALB/c, C3H, or C57BL/6 (B6) mice were transplanted into C3H or B6 mice. The irradiation protocol of (2+2) Gy for 3 days was found to be insufficient to enable the complete removal of recipient immunocompetent cells, since donor-reactive T cells were observed in the recipient spleens and many recipient-type NK and CD4(+) cells were also detected in the recipient hematolymphoid tissues. In all the combinations, the highest survival rate was achieved in the recipients irradiated with (6+6) or (6.5+6.5) Gy with a 4 h interval. In the surviving mice, the hematolymphoid tissues had been fully reconstituted with donor cells.

Successful allogeneic bone marrow transplantation (BMT) by injection of bone marrow cells via portal vein: stromal cells as BMT-facilitating cells.

We examined the importance of the coadministration of bone marrow (BM) stromal cells with BM cells via the portal vein. A significant increase in the number of day-14 colony-forming unit-spleen (CFU-S) was observed in the recipient mice injected with hemopoietic stem cells (HSCs) along with donor BM stromal cells obtained after three to four weeks of culture. Histological examination revealed that hematopoietic colonies composed of both donor hemopoietic cells and stromal cells coexist in the liver of these mice. However, when donor HSCs plus BM stromal cells were administered i.v., neither the stimulatory effects on CFU-S formation nor the hemopoietic colonies in the recipient liver were observed. These findings suggest that the interaction of HSCs with stromal cells in the liver is the first crucial step for successful engraftment of allogeneic HSCs. It is likely that donor stromal cells and HSCs trapped in the liver migrate into the recipient BM and spleen, where they form CFU-BM and CFU-S, respectively.

Changes in ganglioside contents, plasma sialic acid and cAMP levels in experimental hepatoma in mice.

The present study was designed to assess whether changes in glycolipids and cyclic AMP contents might serve as markers for the diagnosis of malignancy in the liver. The experimental model was a transplantable murine hepatoma. Experimental mice were divided into three groups: (1) a therapeutic group, which had been transplanted with hepatoma and treated with the antimetabolism drug 5-fluorouracil (0.2 mg/day i.p.), (2) a control group, which had been transplanted with hepatoma and treated with 0.2 ml 0.9% NaCl/day and (3) a normal group of mice. The ganglioside and cAMP contents in the hepatoma tissue, plasma cAMP, total- and lipid-bound sialic acid levels and red blood cell membrane sialic acid levels were determined. Results showed that the ganglioside content, total and lipid-bound sialic acid levels in the control group were significantly higher than those in the livers of normal mice (p < 0.01) while these respective values in the therapeutic group were significantly lower than those in the control group (p < 0.01). The cAMP levels of tumor tissues and plasma in the control group were lower than those in normal mice. No significant difference in red blood cell membrane sialic acid content was observed between the therapeutic and control groups though levels for both were higher than those in normal mice. These results indicate that ganglioside content and sialic acid levels in hepatoma tissues were significantly elevated, and cAMP levels in hepatoma tissues were significantly decreased during proliferation and abnormal differentiation.

[Effects of red ginseng on the congestive heart failure and its mechanism].

Forty-five patients with class IV cardiac function were divided into three groups: group I (digoxin group), group II (Red Ginseng group) and group III (Red Ginseng plus digoxin group). Each group consisted of 15 cases. After treatment, the improvement of the hemodynamical and biochemical indexes of group II and group III were greater than those of group I, and group III was the most significant amongst all. The results suggested that Red Ginseng and digoxin had synergism for treatment of congestive heart failure, and Red Ginseng was an effective and safe adjuvant without any side effects.