Facile synthesis of phosphorus and nitrogen co-doped carbon dots with excellent fluorescence emission towards cellular imaging.

Fluorescent carbon nanomaterials have attracted increasing attention owing to their unique photoluminescence properties, good biocompatibility and low toxicity in bioimaging as well as biosensing. Heteroatom doping is usually used to improve photoluminescence properties by tuning the functional groups and the particle size domain effect, thus leading to redshifted emission. Here, we report a straightforward strategy for the fabrication of a mixture of fluorescent phosphorus and nitrogen carbon nanodots (P,N-CDs) followed by separating two kinds of fluorescent fractions based on their different negative charges. Such a one-pot hydrothermal method using formamide, urea and hydroxyethylidene diphosphonic acid as the precursor yields fluorescent P,N-CDs. Specifically, blue-emitting CDs (bCDs) and green-emitting CDs (gCDs) were separated by using column chromatography. The quantum yields of bCDs and gCDs were 20.33% and 1.92%, respectively. And the fluorescence lifetimes of bCDs and gCDs were 6.194 ns and 2.09 ns, respectively. What is more, the resultant P,N-CDs exhibited low toxicity and excellent biocompatibility. Confocal fluorescence microscopy images were obtained successfully, suggesting that P,N-CDs have excellent cell membrane permeability and cellular imaging. This work provides a promising fluorescent carbon nanomaterial with tunable emission as a probe for versatile applications in bioimaging, sensing and drug delivery.

[Ginsenoside Rg3 Regulates Cisplatin Resistance in Gastric Cancer by Wnt/ß-catenin Signaling Pathway].

Objective To investigate the inhibitory effect of ginsenoside Rg3 combined with cisplatin (DDP) on DDP-resistant cell line SGC-7901/DDP and their molecular mechanism.Methods SGC-7901/DDP cells were divided into four groups including a control group,a ginsenoside Rg3 (40 µg/ml) treatment group,a DDP (1.40 µg/ml) treatment group,and a drug combination treatment group.The proliferation ability of SGC-7901/DDP cells was detected by MTT,EdU,and colony formation assays.The apoptosis ability of SGC-7901/DDP cell was detected by flow cytometry and Hoechst 33342 staining.The protein levels of apoptosis-related markers were detected by Western blotting.The migration ability of SGC-7901/DDP cells was detected by wound healing and Transwell assays.The expression levels of proteins in epithelial-mesenchymal transformation (EMT) and Wnt/ß-catenin signaling pathway were determined by Western blotting and immunofluorescence staining.Results Compared with the ginsenoside Rg3 or the DDP treatment groups,the drug combination treatment group inhibited the proliferation (t=8.062,P=0.001;t=7.090,P=0.002),colony formation (t=8.062,P=0.001;t=6.144,P=0.004),and migration (t=7.424,P=0.002;t=4.317,P=0.013),and promoted the apoptosis (t=5.530,P=0.031;t=6.036,P=0.026) of SGC-7901/DDP cells.Compared with the ginsenoside Rg3 and the DDP treatment groups,the drug combination treatment group down-regulated the expression levels of EMT-associated proteins including vimentin (t=24.450,P<0.001;t=14.750,P<0.001),Snail (t=29.640,P<0.001;t=70.700,P<0.001),Slug (t=89.230,P<0.001;t=87.360,P<0.001),matrix metalloproteinase (MMP) 2 (t=84.540,P<0.001;t=67.120,P<0.001),and MMP9 (t=19.010,P<0.001;t=10.890,P<0.001),as well as those of Wnt/ß-catenin signaling pathway related proteins including Wnt (t=35.480,P<0.001;t=14.670,P<0.001),ß-catenin (t=155.800,P<0.001;t=118.100,P<0.001),C-myc (t=20.870,P<0.001;t=3.334,P=0.029),and cyclin D1 (t=5.007,P=0.008;t=8.347,P=0.001).Meanwhile,it up-regulated the expression of epithelial cells including E-cadherin (t=36.450,P<0.001;t=33.810,P<0.001) and ZO-1 (t=37.060,P<0.001;t=37.030,P<0.001).Conclusion Ginsenoside Rg3 enhanced the sensitivity of SGC-7901/DDP cells to DDP by inhibiting the activity of Wnt/ß-catenin signaling pathway.

Pathological analysis and surgical modalities selection of cT1N0M0 solitary papillary thyroid carcinoma in the isthmus.

BACKGROUND: prognosis, identify clinicopathological characteristics, and determine optimal modalities for cT1N0M0 solitary papillary thyroid carcinoma in the isthmus (PTCI). METHODS: The clinical data of 124 patients with cT1N0M0 solitary PTCI from 3 medical centers were analyzed retrospectively. Of these, 32 participants had undergone total thyroidectomy plus unilateral central neck dissection, 36 had received total thyroidectomy plus bilateral central neck dissection, 24 had less-than-total thyroidectomy plus unilateral central neck dissection, and 32 had less-than-total thyroidectomy plus bilateral central neck dissection. We compared the effects of different surgical modalities and clinicopathological characteristics on the prognosis of cT1N0M0 solitary PTCI. RESULTS: There was no significant difference in postoperative recurrence-free survival between participants who received different extents of central region lymph node dissection and thyroidectomies (P>0.05). Temporary hypocalcemia occurred in participants who underwent total thyroidectomy plus bilateral central neck dissection [chi-square (χ2) =7.87, P=0.005]. Tumors with primary lesions ≥0.55 cm were prone to have central lymph node metastasis [95% confidence interval (CI): 0.51 to 0.71, P=0.047]. Multiple logistic analysis suggested that age over 55 years [odds ratio (OR) =11.90, 95% CI: 1.36 to 104.03, P=0.025], tumor size greater than 0.55 cm (OR =4.16, 95% CI: 1.28 to 13.52, P=0.018), and absence of nodular goiter (OR =2.57, 95% CI: 1.05 to 6.32, P=0.04) were risk factors for central lymph node metastasis of patients with cT1N0M0 solitary PTCI. CONCLUSIONS: Less-than-total thyroidectomy is recommended for patients with cT1N0M0 solitary PTCI. Central lymph node dissection is recommended for patients who are prone to have central occult lymph node metastases with tumor size ≥55 cm, older than 55 years, and without nodular goiter.

Effects of screw configuration on chemical properties and ginsenosides content of extruded ginseng.

BACKGROUND: The purpose of this study was to investigate the effects of screw configuration on chemical properties and ginsenosides content of extruded ginseng and to select the most suitable screw configuration for the processing of ginseng. METHOD: The extrusion conditions were set as follows: moisture content (20%), barrel temperature (140°C), screw speed (200 rpm), and feeding rate (100 g/min). RESULT: The extruded ginseng of screw configuration 6 has the highest DPPH free radical scavenging rate, reducing power and total phenol, which is the most suitable configuration for the development of ginseng extract products. In addition, the extruded ginseng of screw configuration 9 has the highest content of total saponin, and the content of rare ginsenoside Rg3 which is scarcely present in the ginseng raw material powder was significantly increased. This intended that twin-screw extrusion process enables the mutual conversion between ginsenosides and rare ginsenoside Rg3 had achieved. CONCLUSION: The extrusion process promotes the development and utilization of ginseng and provides theoretical basis for the design and development of screw configuration of twin-screw extruded ginseng.

The 6q25.1 rs2046210 polymorphism is associated with an elevated susceptibility to breast cancer: A meta-analysis of 261,703 subjects.

BACKGROUND: Several genome-wide association studies already explored the associations between 6q25.1 rs2046210 polymorphism and breast cancer (BC), but the results of these studies were not consistent. Thus, we conducted a meta-analysis of relevant studies to better analyze the effects of rs2046210 polymorphism on individual susceptibility to BC. METHODS: PubMed, Web of Science, and Embase were searched for eligible studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Totally 21 studies with 261,703 subjects were analyzed. A significant association with BC was observed for the rs2046210 polymorphism in GG versus GA +AA (dominant comparison, p < 0.0001, OR = 0.78, 95% CI 0.73-0.83), AA versus GG + GA (recessive comparison, p < 0.0001, OR = 1.21, 95% CI 1.18-1.24), GA versus GG + AA (overdominant comparison, p < 0.0001, OR = 1.12, 95% CI 1.08-1.16), and G versus A (allele comparison, p < 0.0001, OR = 0.86, 95% CI 0.82-0.89). Further subgroup analyses yielded similar positive results in both Asians and Caucasians. CONCLUSION: In summary, our findings suggested that the rs2046210 polymorphism may serve as a potential genetic biomarker of BC in both Asians and Caucasians.

Effects of extrusion conditions on chemical properties of extruded white ginseng root hair.

BACKGROUND: This study was to investigate the significant effects of extrusion process variables on chemical properties of extruded white ginseng root hair. The extrusion conditions were set as follows: barrel temperature (110 and 140 °C), moisture content (20 and 30%) and screw speed (200 and 300 rpm). The powder of white ginseng root hair was extruded as L8 (27 ) orthogonal experimental design. RESULTS: The crude saponin and acidic polysaccharide contents of extrudate were significantly higher than those of raw material after extrusion. In addition, antioxidant properties were also increased, while reducing sugar content was markedly lower than that of raw material. Moisture content was the most significant factor affecting the reducing sugar, acidic polysaccharide and total phenolic contents, and 2,2-diphenyl-1-picrylhydrazyl scavenging activity. Barrel temperature significantly affected reducing power, and screw speed significantly influenced crude saponin content. CONCLUSIONS: The extrusion process aided in improving the amount of beneficial compounds from white ginseng root hair. © 2018 Society of Chemical Industry.

Isolation and characterization of a protease from the Actinidia arguta fruit for improving meat tenderness.

An protease from Actinidia arguta for improving meat tenderness was purified, characterized from wild A. arguta fruit by ammonium sulfate precipitation, Sephdex G-25 gel filtration chromatography, and DEAE Sepharose Fast Flow ion exchange chromatography, and its activity was investigated. The purified protease was subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis to obtain a single band of protease. The protease was purified successfully, and found to have a molecular weight of 23.8 kDa (mass spectrometry). The specific activity of the purified protease reached 53,428 U/mg with a 25.5-fold purification factor and 9% activity recovery. Based on N-terminal sequencing results, the A. arguta protease was derived from the class of actinidia proteases that have an N-terminal sequence of VLPDY VDWRS AGAVV. The protease was effective for tenderizing beef and decomposing actomyosin, suggesting the potential application for improving meat tenderness.

Cytotoxic anthraquinone dimers from Melandrium firmum.

Two new anthraquinone dimers, melrubiellin A (1) and melrubiellin B (2), were isolated from the aerial part of Melandrium firmum Rohrbach, along with seven known compounds (3-9). The structures of these compounds were elucidated by spectral analyses, including 1D and 2D NMR (COSY, HMQC, HMBC and NOESY) experiments. Compound 1 and 2 exhibited significant cytotoxicity towards HeLa, NCI-H460, Hep G2, Hep 3B and MKN-28 cell lines with IC50 values ranging from 5.26 to 81.16 µM.

Expression of Akt kinase-interacting protein 1, a scaffold protein of the PI3K/PDK1/Akt pathway, in pancreatic cancer.

OBJECTIVES: Akt kinase-interacting protein 1 (Aki1) has been reported to be a scaffold protein of the PI3K (phosphoinositide 3-kinase)/PDK1 (3-phosphoinositide-dependent protein kinase)/Akt pathway and to interact with epidermal growth factor receptor signaling. Although Aki1 has been reported to be expressed in lung cancer, the significance of its expression in pancreatic cancer has not been clarified. METHODS: The expression of Aki1 and its associated proteins was assayed in pancreatic cancer cell lines, and its involvement in cell viability was examined by treatment with Aki1 small interfering RNA. We also assessed the immunohistochemical expression of Aki1 in tissue samples from 60 patients with pancreatic cancer. RESULTS: All of the pancreatic cancer cell lines expressed Aki1 and its associated proteins at various levels. Treatment with Aki1 small interfering RNA or PI3K inhibitor inhibited the viability of Panc1 cells. Silencing of Aki1 in Panc1 cells reduced the phosphorylation of Akt and increased the phosphorylation of cleaved PARP. The Aki1 was expressed in 25 (42%) of the 60 pancreatic cancers, but there was no correlation between Aki1 expression and clinicopathologic parameters. We observed a statistically significant correlation between Aki1 and p-Akt expression (P = 0.016). CONCLUSIONS: Inhibition of the Aki1-Akt axis may be a therapeutic target in some patients with pancreatic cancer.

Improved anti-tumor efficiency against prostate cancer by docetaxel-loaded PEG-PCL micelles.

This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol (PEG)2000-polycaprolactone (PCL)2600 micelles on hormone-refractory prostate cancer (HRPC). By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel (DTX)-loaded mPEG-PCL micelles (DTX-PMs), with the purpose of eliminating side effects of the commercial formulation (Tween 80) and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of (8.72±1.05)%, and an encapsulation efficiency of (98.1±8.4)%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei®. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei®, the DTX-PMs dramatically reduced the prostate specific antigen (PSA) level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.

Tunica Vaginalis Pedicle Flap for Reconstruction of Anterior Urethral Stricture.

OBJECTIVE: To evaluate the intermediate-term clinical efficacy and success rate of tunica vaginalis (TV) pedicle flap for reconstruction of bulbo-penile urethral stricture. METHODS: We assessed the medical records of 15 male patients who had undergone TV pedicle flap urethroplasty for reconstruction of anterior urethral stricture between January 2006 and December 2011. The surgical outcome was assessed by comparison of four parameters including the maximum flow rate (Qmax ), international prostate symptom score (IPSS), residual urine (RU) and quality of life (QOL) in all patients pre- and postoperatively. Moreover, pre- and postoperative retrograde urethrography films were compared in all patients. t-test was used for data analysis. RESULTS: The mean patient age was 38.1 ± 9.3 years (range: 25-55), mean stricture length was 4.2 ± 1.1 cm (range: 3-6.1 cm), and the mean follow up time was 14.6 ± 1.9 months (range: 12-18) months. There was a statistically significant difference between Q(max) , IPSS, RU and QOL pre- and postoperatively (P < 0.01). The clinical success rate in this study was 86.6% (13/15). The early complication was one case of wound infection and subsequent wound dehiscence, one case of hematoma formation in another patient, which did not have any influence in the long-term clinical outcome. CONCLUSION: At intermediate-term follow up, TV pedicle flap urethroplasty has a high clinical success rate with low complication. However, a large clinical trial with long-term follow up is needed to confirm the result.

[Urethroplasty with pedunculated preputial flap and testicular tunica vaginalis for long anterior urethral stricture: A case report and review of the literature].

OBJECTIVE: To explore the treatment of urethral stricture. METHODS: We retrospectively studied the clinical data of 1 case of long anterior urethral stricture treated by urethroplasty with pedunculated preputial flap and testicular tunica vaginalis, and summarized the treatment of the disease with review of the relevant literature. RESULTS: The operation was smooth and successful, and no such complications as fistula and urethral stricture were found during the follow-up. CONCLUSION: Urethroplasty with pedunculated preputial flap and testicular tunica vaginalis as a substitute is feasible for the treatment of urethral stricture. The key to a successful operation is the proper choice of a urethral substitute.

[Study on the alkaloids from the stem of Zanthoxylum dissitum].

OBJECTIVE: To study the alkaloids from the stems of Zanthoxylum dissitum. METHODS: Added ammonia to the 0.5% HCl extract solution of the plants until the pH was 11 to collect the total alkaloids. Using the chromatography of alumina and silica gel to separate the alkaloids. According to the physicochemical properties and spectral analysis to elucidate the structures of the constitutes. RESULTS: Four compounds were isolated and identified as nitidine (I), sanguinarine (II), zanthobungeanine (III), dictamnine (IV). CONCLUSION: Besides dictamnine, three others are isolated from the rhizome of the plant for the first time.

[Expression of cyclooxygenase-2 and vascular endothelial growth factor in human prostate cancer and its significance].

OBJECTIVE: To evaluate expressions of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in primary prostate cancer and its clinical significance. METHODS: Expressions of COX-2 and VEGF were detected by immunohistochemical assay in tissues of 40 prostate cancer and 10 benign prostatic hyperplasia samples. RESULTS: COX-2 and VEGF levels in prostate cancer were much higher than those in BPH. The degrees of cancer malignancy and invasion positively correlated with the expressions of COX-2 and VEGF. COX-2 level positively correlated with VEGF level. CONCLUSION: The abnormal expression of COX-2 plays an important role in the development of primary prostate cancer. COX-2 and VEGF are good molecular markers of prostate cancer which are hopeful to be used for the assistant diagnosis and the prediction of prognosis of prostate cancer.

[The cytotoxicity and mechanism of CIK cells to breast cancer cells ZK-75-1].

AIM: To study the cytotoxicity and mechanism of cytokine-induced killer (CIK) cells to breast cancer cell line ZK-75-1. METHODS: The morphological changes of ZK-75-1 cells were observed by HE staining. The apoptosis of ZK-75-1 cell line was examined by TUNEL staining. The expression of P53, P16, C-myc, Bcl-2 and Bax was determined by immunocytochemical staining. RESULTS: The result of HE staining revealed that CIK cells moved toward the target cells, forming typical rosette cells. Granule-like substances appeared in cytoplasm of tumor cells, but only granule-shape patch was found in some tumor cells while breast cancer cells as control grew well. TUNEL staining indicated that the cells in control group were not stained or dyed well-distributed light blue. As the cells in experiment group became smaller, mucleoluser or perinuclear was dyed deep blue. The apoptotic rate of ZK-75-1 cells cocultured with CIK cells was increased after 4-12 hours and was decreased after 12-24 hours, with a significant difference compared with control group (P<0.01). Immunocytochemical staining showed that the expression of p53, p16, C-myc and Bcl-2 proteins in CIK group declined but the expression of Bax protein increased with the passage of time, which was significantly different compared with control (P<0.01). CONCLUSION: The mechanism of killing ZK-75-1 cells by CIK cells is closely related to the downregulation of the expression of P53, P16, c-myc and Bcl-2 proteins and to the upregulation of the expression of Bax protein. It also has close relation with the time of exposure to CIK cells.

Induction of tolerance in quadruple chimeric mice.

Human cord blood (CB) contains hematopoietic stem cells and progenitors. Because the major limitation to a widespread use of CB for transplantation lies in its limited volume, it is necessary to combine the CB from several donors. In this study, we show that lethally irradiated mice can be reconstituted with the injection of a mixture of T cell-depleted bone marrow cells (BMCs; total, 3 x 10(6)) obtained from three fully allogeneic mouse strains in two different mouse combinations. A higher survival rate was obtained in the triple injection group than in mice injected with BMCs (1 x10(6)) obtained from a single mouse strain. In the mixed chimeric mice, three kinds of donor-type and recipient-type cells were detected in all the hematopoietic organs 1 month after bone marrow transplantation (BMT). Mixed-lymphocyte reaction showed that the tolerance to both recipient-type and donor-type major histocompatibility complex determinants was induced in the chimeric mice. In the peripheral blood (PB) of these mice, only one type of cells from the three different donor strains became dominant in most chimeric mice and reached a stable level about 4 months after BMT. Polymerase chain reaction analyses, however, revealed that the skins from all the donors were accepted even when no cells with their phenotypes could be detected in the PB. These results suggest that both hemato-lymphoid reconstitution and stable tolerance to not only the recipient strain but also all the donor strains can be achieved in chimeric mice, indicating the possibility of mixed CB transplantation in humans.

Long-term immunologic induction of donor-specific tolerance to skin allografts by bone marrow transplant in rabbits.

The induction of donor-specific tolerance to skin allografts was investigated in rabbits using bone marrow transplantation techniques reported to be effective in mice. Various routes of bone marrow transplantation (i.e., intravenous, portal venous, or intraosseous) were also examined. In regimen A, the animals were treated with portal venous injection of bone marrow cells from the donor on day 0 and intravenous injection of bone marrow cells from the same donor on posttransplant day 5. In regimen B, the animals were treated with portal venous and intraosseous injections of donor bone marrow cells on day 0 and intravenous injection of bone marrow cells from the same donor on posttransplant day 5. In regimen C, the animals were given intraosseous injection of donor bone marrow cells on day 0 and intravenous injection of bone marrow cells from the same donor on posttransplant day 5. It was found that regimens B and C were more effective than regimen A in prolonging allograft survival. The results demonstrate that induction of allograft tolerance can be achieved by bone marrow transplantation in a rabbit model. This protocol deserves further study in other large animal models.