Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy

Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood-brain barrier (BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers. Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and glioma-targeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs. The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of menthol-modified casein nanoparticles (M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-M-CA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining of the organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy.

Surface modification of PGP for a neutrophil-nanoparticle co-vehicle to enhance the anti-depressant effect of baicalein

Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. -Acetyl Pro-Gly-Pro (PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles (PGP-SLNs) to facilitate binding to neutrophils . Brain-targeted delivery to the basolateral amygdala (BLA) was demonstrated by enhanced concentration of baicalein in the BLA. An enhanced anti-depressant effect was observed and The mechanism involved inhibition of apoptosis and a decrease in lactate dehydrogenase release. Behavioral evaluation carried out with rats demonstrated that anti-depression outcomes were achieved. The results indicate that PGP-SLNs decrease immobility time, increase swimming time and climbing time and attenuate locomotion in olfactory-bulbectomized (OB) rats. In conclusion, PGP modification is a strategy for targeting the brain with a cell-nanoparticle delivery system for depression therapy.

Comparison of the clinical efficacy of partial hepatectomy combined with biliary intestinal anastomosis and T tube drainage in the treatment of intrahepatic stones / 中国基层医药

Objective To compare the clinical curative effect of partial hepatectomy combined with biliary intestinal anastomosis and T tube drainage in the treatment of intrahepatic stones.Methods 72 patients with intrahe-patic stones were selected and randomly divided into observation group and control group.The observation group received lobectomy of liver +bile duct jejunum anastomosis,the control group received lobectomy of liver +T tube drainage treatment.The operation time,intraoperative blood loss,functional exercise time,length of hospital stay, recurrence rate,clinical efficacy and complications were observed.Results The patients were followed up for 6 -12months.The operative time,blood loss,ambulation exercise time,length of hospital stay in the observation group were (158.29 ±32.53)min,(161.42 ±11.75)mL,(3.61 ±0.28)d,(5.31 ±1.17)d,which were significantly more than those in the control group[(127.57 ±26.38)min,(78.29 ±8.36)mL,(2.25 ±0.56)d,(4.86 ± 2.39)d].The recurrence rate of stone of the observation group during the postoperative follow -up was 5.56%, which was significantly lower than 16.67% of the control group (t =4.328,7.196,2.174,2.259,1.862,all P <0.05).The excellent and good rate of the observation group was 94.44%,which was higher than 83.33% of the control group,the difference was statistically significant (χ2 =1.257,P <0.05).6 cases in the observation group had complications (16.67%),including 1 case of incision infection,subphrenic infection in 2 cases,bile leakage in 2 cases,1 case of pulmonary infection.15 cases in the control group had postoperative complications (41.67%), including 3 cases of wound infection,bile leakage in 4 cases,3 cases of biliary tract bleeding,abdominal bleeding in 1 case,2 cases of pulmonary infection,subphrenic infection in 1 case,pleural effusion in 1 case,the difference between the two groups was significant (χ2 =2.291,P <0.05).Conclusion Liver resection is an effective method for treatment of intrahepatic bile duct stones,on the basis of liver resection by intestinal anastomosis in the treatment of intrahepatic bile duct stone long -term effect is better,which can effectively prevent recurrence of the intrahepatic bile duct stone and bile duct cancer,widely used in patients with indications for clinical physicians.

Study on Anti-tumor Activities of Trichosanthin Mediated by Low Molecular Weight Protamine / 广州中医药大学学报

Objective To investigate the anti-tumor activities of cell-penetrating peptide ( CPP) - mediated trichosanthin ( TCS) , which is a recombinant protein obtained from Radix Trichosanthis. Methods Cysteine residue was introduced to the C-terminus of TCS by protein recombinant technique, and then with the newly-formed terminal as the modification site, TCS was coupled with CPP. As a target protein, CPP-mediated TCS was isolated and purified by affinity chromatography. The expression of the target protein and its responsiveness to reducing substances were detected by using the sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The cellular uptake rate of CPP-mediated TCS was determined by using cell uptake test, and its anti-tumor activity was measured by using methyl thiazolyl tetrazolium (MTT) assay. Results The TCS-CPP compound had been successfully developed in this study, and showed certain reducing responsiveness. After modified with CPP, TCS had higher cellular uptake rate and stronger anti-tumor effect on HeLa and MCF-7 cells. Conclusion TCS modified by CPP can enhance the anti-tumor activities of TCS.

The expression and clinical significance of serum Golgi protein 73 in hepatocellular carcinoma / 中国医师杂志

Objective To investigate the expression of serum Golgi protein 73 in hepatocellular carcinoma(HCC) and analyze the clinical significance.Methods The expression of GP73 was measured by ELISA in 75 HCC ,30 chronic hepatitis and normal con -trols.Results The serum concentrations of GP73 were (128.3 ±33.6)μg/L,(80.3 ±19.2)μg/L and (78.3 ±18.5)μg/L in the HCC, chronic hepatitis patients and normal controls .The serum level of GP73 was significantly higher in HCC than those with chronic hepatitis and healthy controls .GP73 expression was positively correlated with clinical stage , humor size and metastasis.The positive rate of GP73 in stage was 60%,higher than the AFP positive rate(33%).Conclusions The serum level of GP73 is high in HCC and was helpful for distinguishing benign and malignant liver diseases .GP73 can be used as a diagnostic marker for HCC .

Cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy / 药学学报

To develop a cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy, we prepared the AVPI-LMWP/pTRAIL self-assembled complexes containing a therapeutic combination of peptide drug AVPI and DNA drug TRAIL. The chimeric apoptotic peptide AVPI-LMWP was synthesized using the standard solid-phase synthesis. The cationic AVPI-LMWP could condense pTRAIL by electrostatic interaction. The physical-chemical properties of the AVPI-LMWP/pTRAIL complexes were characterized. The cellular uptake efficiency and the inhibitory activity of the AVPI-LMWP/pTRAIL complexes on tumor cell were also performed. The results showed that the AVPI-LMWP/pTRAIL complexes were successfully prepared by co-incubation. With the increase of mass ratio (AVPI-LMWP/DNA), the particle size was decreased and the zeta potential had few change. Agarose gel electrophoresis showed that AVPI-LMWP could fully bind and condense pTRAIL at a mass ratio above 15:1. Cellular uptake efficiency was improved along with the increased ratio of W(AVPI-LMWP)/WpTRAIL. The in vitro cytotoxicity experiments demonstrated that the AVPI-LMWP/pTRAIL (W:W = 20:1) complexes was significantly more effective than the pTRAIL, AVPI-LMWP alone or LMWP/pTRAIL complexes on inhibition of HeLa cell growth. Our studies indicated that the AVPI-LMWP/pTRAIL co-delivery system could deliver plasmid into HeLa cell and induce tumor cell apoptosis efficiently, which showed its potential in cancer therapy using combination of apoptoic peptide and gene drugs.

Correlation between Pet-CO2 and PaCO2 in morbidly obese patients during anesthesia for laparoscopic gastric bypass surgery / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the correlation between arterial partial pressure of CO2 (PaCO2) and end expiratory tidal partial pressure of CO2 (Pet-CO2) in morbidly obese patients during anesthesia for laparoscopic gastric bypass surgery.</p><p><b>METHODS</b>Forty morbidly obese patients with a body mass index (BMI) between 35 and 50 kg/m(2) underwent laparoscopic gastric bypass surgery under general anesthesia. PaCO2 and Pet-CO2 were measured after intubation and before induction of pneumoperitoneum (T0), at 30 min (T1), 60 min (T2), and 120 min (T3) during pneumoperitoneum, and at 30 min (T4) and 60 min (T5) after deflation.</p><p><b>RESULTS</b>At each time point of measurement, Pet-CO2 was lower than PaCO2 in all the patients. PaCO2 and Pet-CO2 were positively correlated before, during, and after pneumoperitoneum (P<0.05). At a moderate pressure of CO2 pneumoperitoneum (16 mmHg), the level of correlation between PaCO2 and Pet-CO2 at T1, T2, and T3 differed from that before and after post-pneumoperitoneum.</p><p><b>CONCLUSIONS</b>PaCO2 and Pet-CO2 are closely correlated during a moderate CO2 pneumoperitoneum in morbidly obese patients undergoing laparoscopic gastric bypass surgery.</p>

Effects of intraabdominal administration of pseudomonas acerug vaccine on cytoimmunity in advanced gastric cancer patients / 中华普通外科杂志

ObjectiveTo evaluate the safety and effects of pseudomonas aerug PA-MSHA vaccine on cytoimmunity in advanced gastric cancer patients. MethodsSeventy two patients with advanced gastric cancer were randomly divided into experimental group and control group. Tumor bed was treated intraoperatively by pseudomonas vaccine injection in experimental group.The venous bloods were sampled prior to surgery (preoperative) and on days 10,20,and 30 postoperatively.The total lymphocyte count and lymphocyte subpopulations were detected while the postoperative complications and adverse drug reaction were observed,prognosis was evaluated. ResultsThe total lymphocyte count(P =0.042) and the counts ofCD3+ lymphocyte(P =0.027) and NK cell increased (P =0.012) obviously in experimental group.CD8+ lymphocyte decreased(P =0.037),but the counts of CI4+ lymphocyte and CD4+/CD8+ were not significantly different.Complications were not significantly different in the two groups.One year survival rate was longer ( 94.9％ ) in experimental group than that in the control group ( 83.3％ ) ( P =0.022 ).ConclusionsPeritoneal cavity administration with pseudomonas aerug vaccine was safe,and effectively helps regulate cytoimmunity in postoperative patients of advanced gastric carcinoma.