Endostar-loaded PEG-PLGA nanoparticles: in vitro and in vivo evaluation

Endostar, a novel recombinant human endostatin, which was approved by the Chinese State Food and Drug Administration in 2005, has a broad spectrum of activity against solid tumors. In this study, we aimed to determine whether the anticancer effect of Endostar is increased by using a nanocarrier system. It is expected that the prolonged circulation of endostar will improve its anticancer activity. Endostar-loaded nanoparticles were prepared to improve controlled release of the drug in mice and rabbits, as well as its anticancer effects in mice with colon cancer. A protein release system could be exploited to act as a drug carrier. Nanoparticles were formulated from poly (ethylene glycol) modified poly (DL-lactide-co-glycolide) (PEG-PLGA) by a double emulsion technique. Physical and release characteristics of endostar-loaded nanoparticles in vitro were evaluated by transmission electron microscopy (TEM), photon correlation spectroscopy (PCS), and micro bicinchoninic acid protein assay. The pharmacokinetic parameters of endostar nanoparticles in rabbit and mice plasma were measured by enzyme-linked immunosorbent assay. Western blot was used to detect endostatin in different tissues. To study the effects of endostar-loaded nanoparticles in vivo, nude mice in which tumor cells HT-29 were implanted, were subsequently treated with endostar or endostar-loaded PEG-PLGA nanoparticles. Using TEM and PCS, endostar-loaded PEG-PLGA nanoparticles were found to have a spherical core-shell structure with a diameter of 169.56 ± 35.03 nm. Drug-loading capacity was 8.22% ± 2.35% and drug encapsulation was 80.17% ± 7.83%. Compared with endostar, endostar-loaded PEG-PLGA nanoparticles had a longer elimination half-life and lower peak concentration, caused slower growth of tumor cell xenografts, and prolonged tumor doubling times. The nanoparticles changed the pharmacokinetic characteristics of endostar in mice and rabbits, thereby reinforcing anticancer activity. In conclusion, PEG-PLGA nanoparticles are a feasible carrier for endostar. Endostar-loaded PEG-PLGA nanoparticles seem to have a better anticancer effect than conventional endostar. We believe that PEG-PLGA nanoparticles are an effective carrier for protein medicines

Suitable carriers for encapsulation and distribution of endostar: comparison of endostar-loaded particulate carriers

Weijie Chen, Sanyuan HuDepartment of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, People's Republic of ChinaBackground: Particulate carriers are necessary to control the release of endostar and prolong its circulation in vivo. The purpose of this study was to identify a suitable carrier for the capsulation and delivery of endostar.Methods: We prepared a series of poly (DL-lactide-co-glycolide) (PLGA) and poly (ethylene glycol) (PEG)-modified PLGA (PEG-PLGA) particulate carriers, and then characterized them according to their ability to prolong the circulation of endostar, their physicochemical properties, endostar-loading content, and in vitro and in vivo particulate carrier release profiles.Results: All the particulate carriers had spherical core shell structures. The PEG-PLGA material and nanosize range appeared to enable the carriers to encapsulate more endostar, release endostar faster in vitro, and accumulate more endostar in vivo. The drug loading capacity of PEG-PLGA and PLGA nanoparticles was 8.03% ± 3.41% and 3.27% ± 5.26%, respectively, and for PEG-PLGA and PLGA microspheres was 15.32% ± 5.61% and 9.21% ± 4.73%. The cumulative amount of endostar released from the carriers in phosphate-buffered saline over 21 days was 23.79%, 20.45%, 15.13%, and 10.41%, respectively. Moreover, the terminal elimination half-life of endostar in the rabbit was 26.91 ± 7.93 hours and 9.32 ± 5.53 hours in the PEG-PLGA group and the PLGA nanoparticle group. Peak endostar concentration was reached at day 7 in the group treated with subcutaneous injection of PEG-PLGA microspheres and at day 14 in the group receiving subcutaneous injection of PLGA microspheres. Endostar was detectable in vivo in both groups after injection of the particulate carriers.Conclusion: PEG-PLGA nanoparticles might be better than other nanoparticulate carriers for encapsulation and distribution of endostar.Keywords: poly(DL-lactide-co-glycolide), nanoparticle, microsphere, endostar, peptide deliver

Endovascular stent-graft placement and coil embolization for an anomalous splenic artery aneurysm

Aneurysms of the splenic artery originating anomalously from the superior mesenteric artery are extremely rare; however, they are clinically important because of the potential for fatal rupture and particular anatomical location. Most previous cases were managed by open surgical intervention. We present a case of an anomalous splenic artery aneurysm, which was successfully treated with endovascular stent graft placement and coil embolization. This appears to be a promising minimally invasive approach to manage this rare entity. Also, we review the literature of aneurysms of the splenic artery arising from the superior mesenteric artery

Spontaneous retroperitoneal hematoma associated with iliac vein rupture

ObjectiveSpontaneous retroperitoneal hematoma (SRH) associated with iliac vein rupture is a rare but life-threatening emergency with high operative mortality. This study summarizes our experience in providing diagnostic and therapeutic management for this rare clinical entity.MethodsBetween May 2002 and May 2009, nine patients were admitted to our hospital for SRH and acute deep venous thrombosis (DVT). Medical data for demographics, clinical presentation, auxiliary examinations, treatment modalities, outcomes, and follow-up were retrospectively analyzed.ResultsNine patients (8 women, 1 man) were enrolled in this study. All were aged >45 years (range, 46-70 years). The common clinical manifestations were sudden onset of left lower abdominal or lumbar pain, swelling of the left lower extremity, anemia, and hypotension. Most patients were diagnosed by duplex ultrasound imaging and computed tomography scan. Three patients were treated conservatively, and six underwent surgical or combined treatments, comprising 2 repairs of iliac vein, 1 iliac vein ligation and Palma-Dale bypass graft, 1 pelvic vein ligation, 1 removal of hematoma, and 1 repair of iliac vein, thrombectomy, and endovascular stent placement. The iliac vein ruptured in five patients. May-Thurner syndrome was found in three patients. One patient died after surgery (operative mortality, 16.7%). Postoperative morbidity was 50%. Mean volume of perioperative blood transfusion was 900 ± 640 mL (range, 0-2000 mL). Mean lengths of stay were 2.7 ± 1.4 days (range, 2-5 days) in the intensive care unit and 16.9 ± 2.4 days (range, 14-21 days) in the hospital. Eight patients were postoperatively treated with 6 months of warfarin. Mean follow-up was 30.5 ± 15.0 months (range, 6-50 months). The occurrence rate of chronic venous insufficiency was 87.5% during follow-up.ConclusionsSRH with concomitant DVT, especially in women aged >45, should be considered in patients with sudden lower abdominal or lumbar pain, leg swelling, anemia, and shock. Spontaneous iliac vein rupture and the presence of May-Thurner syndrome should be considered in these patients. Surgical interventions were associated with high mortality and morbidity. In our experience, conservative therapy was safer than open surgical procedures

Role of Bile Acids in Bariatric Surgery

Bariatric surgery has been proved to be effective and sustainable in the long-term weight-loss and remission of metabolic disorders. However, the underlying mechanisms are still far from fully elucidated. After bariatric surgery, the gastrointestinal tract is manipulated, either anatomically or functionally, leading to changed bile acid metabolism. Accumulating evidence has shown that bile acids play a role in metabolic regulation as signaling molecules other than digestive juice. And most of the metabolism-beneficial effects are mediated through nuclear receptor FXR and membrane receptor TGR5, as well as reciprocal influence on gut microbiota. Bile diversion procedure is also performed on animals to recapitulate the benefits of bariatric surgery. It appears that bile acid alteration is an important component of bariatric surgery, and represents a promising target for the management of metabolic disorders

The Plasma LncRNA Acting as Fingerprint in Hilar Cholangiocarcinoma

Background & Aims: Current studies have indicated that long non-coding RNAs (lncRNAs) could act as tumor biomarkers for disease diagnosis and prognosis prediction. In this study, we mainly focused on determining the expression of circulating lncRNAs in patients suffering for hilar cholangiocarcinoma (HC), aiming to reveal the potential lncRNA as a fingerprint. Methods: A total 12 lncRNAs were previously proven to be aberrantly expressed in HC tumor tissues. All of the 12 lncRNAs were selected as candidate targets for subsequent circulating lncRNA assay. The candidate lncRNAs were validated by qRT-PCR arranged in training and validation sets. The risk score analysis was employed. Data was presented with receiver operating characteristic curve (ROC). Results: Circulating PCAT1, MALAT1, and CPS1-IT1 were significantly increased in plasma samples of HC patients in both the training set and validation set. Through ROC analysis, we found that the three plasmatic lncRNAs presented the area under ROC curve value (AUC) as 0.784, 0.860, and 0.677. Further combination with the three factors indicated a higher power (AUC, 0.893; sensitivity, 85.5%; specificity, 93.2%). Conclusion: This was the first time to reveal the potential circulating fingerprints for predicting HC. PCAT1, MALAT1, and CPS1-IT1 may act as novel early diagnosis biomarkers for predicting HC

Application of Acellular Tissue Matrix for Enhancement of Weak Abdominal Wall in Animal Model

Background. Abdominal wall weakness occurs when the strength of muscle decreases due to physiological reason or iatrogenic injury. However, the treatment of this disease is complicated. Aim. To study the therapeutic effect of acellular tissue matrix (ACTM), compared with the polypropylene mesh. Methods. An abdominal wall weakness model was established in rabbits through motor nerves cutting. The polypropylene mesh and ACTM were implanted in the left and right abdomen sides, respectively. Mechanical testing of abdominal wall muscle and histology and scanning electron microscopy (SEM) evaluation of abdominal tissue explants were performed. Results. In animal model establishment, the abdominal length of healthy and weakened abdominal wall was 17.0 ± 0.7 cm and 19.0 ± 1.2 cm, respectively (P=0.022), and the weak abdominal wall group showed a significant decrease of 1.116 ± 0.221 MPa in tensile stress (P<0.001) and 9.126 ± 2.073% in tensile strain (P<0.001). In materials implantation experiment, compared with polypropylene group, ACTM group decreased 2.409 ± 0.806 MPa after 24 weeks (P<0.001) and 2.319 ± 0.486 MPa after 48 weeks (P<0.001) in tensile stress and increased 15.259% after 24 weeks (P<0.001) and 15.845% after 48 weeks (P<0.001) remarkably in tensile strain. Conclusion. The abdominal wall weakness model in rabbits was successfully established. ACTM is a promising biological material to be possibly further applied in clinical surgery in patients with abdominal wall weakness

Electrospun polyporous VN nanofibers for symmetric all-solid-state supercapacitors

Abstract To promote the energy density of symmetric all-solid-state supercapacitors (SCs), efforts have been dedicated to searching for high-performance electrode materials recently. In this paper, vanadium nitride (VN) nanofibers with mesoporous structure have been fabricated by a facile electrospinning method. Their crystal structures and morphology features were characterized by X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The mesoporous structure of VN nanofibers, which can provide short electrolyte diffusion routes and conducting electron transport pathways, is beneficial to their performance as a supercapacitor electrode. Under a stable electrochemical window of 1.0 V, VN nanofibers possess an excellent mass specific capacitance of 110.8 F/g at a scan rate of 5 mV/s. Moreover, the VN nanofibers were further assembled into symmetric all-solid-state SCs, achieving a high energy density of 0.89 mW·h/cm3 and a high power density of 0.016 W/cm3 over an operating potential range from 0 to 1.0 V. These results demonstrate that VN nanofibers could be potentially used for energy storage devices

CRISPR-Mediated Endogenous Activation of Fibroin Heavy Chain Gene Triggers Cellular Stress Responses in Bombyx mori Embryonic Cells

The silkworm Bombyx mori is an economically important insect, as it is the main producer of silk. Fibroin heavy chain (FibH) gene, encoding the core component of silk protein, is specifically and highly expressed in silk gland cells but not in the other cells. Although the silkworm FibH gene has been well studied in transcriptional regulation, its biological functions in the development of silk gland cells remain elusive. In this study, we constructed a CRISPRa system to activate the endogenous transcription of FibH in Bombyx mori embryonic (BmE) cells, and the mRNA expression of FibH was successfully activated. In addition, we found that FibH expression was increased to a maximum at 60 h after transient transfection of sgRNA/dCas9-VPR at a molar ratio of 9:1. The qRT-PCR analysis showed that the expression levels of cellular stress response-related genes were significantly up-regulated along with activated FibH gene. Moreover, the lyso-tracker red and monodansylcadaverine (MDC) staining assays revealed an apparent appearance of autophagy in FibH-activated BmE cells. Therefore, we conclude that the activation of FibH gene leads to up-regulation of cellular stress responses-related genes in BmE cells, which is essential for understanding silk gland development and the fibroin secretion process in B. mori