OBJECTIVE: To verrify the anti-tumor efficacy and toxicity between juglone (Jug) and Jug-loaded PLGA nanoparticles (Jug-PLGA-NPs). METHODS: Jug-PLGA-NPs were prepared by ultrasonic emulsification. The anti-tumor activity of Jug (2, 3, 4 µg/mL) and Jug-PLGA-NPs (Jug: 2, 3, 4 µg/mL) in vitro was measured by MTT assay and cell apoptosis analysis. The distribution, anti-tumor effect and biological safety in vivo was evaluated on A375 nude mice. RESULTS: With the advantage of good penetration and targeting properties, Jug-PLGA-NPs significantly inhibited proliferation and migration of melanoma cells both in vitro and in vivo (P<0.05 or P<0.01) with acceptable biocompatibility. CONCLUSIONS Jug can inhibit the growth of melanoma but is highly toxic. With the advantage of sustained release, tumor targeting, anti-tumor activity and acceptable biological safety, Jug-PLGA-NPs provide a new pharmaceutical form for future application of Jug.
Animals ; Cell Line, Tumor ; Delayed-Action Preparations/therapeutic use* ; Drug Carriers/therapeutic use* ; Melanoma/pathology* ; Mice ; Mice, Nude ; Nanoparticles ; Naphthoquinones ; Particle Size ; Polylactic Acid-Polyglycolic Acid Copolymer/therapeutic use*

The paclitaxel-loaded and folic acid-modified poly(lactic-co-glycolic acid) nano-micelles(PTX@FA-PLGA-NMs) were prepared by the emulsion solvent evaporation method, and the parameters of paclitaxel-loaded nano-micelles were optimized with the particle size and PDI as evaluation indexes. The morphology of the nano-micelles was observed by transmission electron microscopy(TEM), and the stability, drug loading and encapsulation efficiency were systematically investigated. In vitro experiments were performed to study the cytotoxic effects of nano-micelles, apoptosis, and cellular uptake. Under the optimal parameters, the nano-micelles showed the particle size of(125.3±1.2) nm, the PDI of 0.086±0.026, the zeta potential of(-20.0±3.8) mV, the drug loading of 7.2%±0.75%, and the encapsulation efficiency of 50.7%±1.0%. The nano-micelles were in regular spherical shape as observed by TEM. The blank FA-PLGA-NMs exhibited almost no inhibitory effect on the proliferation and growth of tumor cells, while the drug-loaded nano-micelles and free PTX exhibited significant inhibitory effects. The IC_(50) of PTX@FA-PLGA-NMs and PTX was 0.56 μg·mL~(-1) and 0.66 μg·mL~(-1), respectively. The paclitaxel-loaded nano-micelles were potent in inhibiting cell migration as assessed by the scratch assay. PTX@FA-PLGA-NMs had good pro-apoptotic effect on cervical cancer HeLa cells and significantly promoted the uptake of HeLa cells. The results of in vitro experiments suggested that PTX@FA-PLGA-NMs could target and treat cervical cancer HeLa cells. Therefore, as nanodrug carriers, PTX@FA-PLGA-NMs with anti-cancer activity are a promising nano-system for improving the-rapeutic effects on tumors.
Antineoplastic Agents, Phytogenic/pharmacology* ; Cell Line, Tumor ; Drug Carriers ; Female ; Folic Acid ; Glycolates ; HeLa Cells ; Humans ; Micelles ; Paclitaxel ; Particle Size ; Uterine Cervical Neoplasms/drug therapy*

Animals ; Antigens, Surface/genetics* ; Cell Communication/genetics* ; Copulation/physiology* ; Fallopian Tubes/metabolism* ; Female ; Fertilization/genetics* ; GPI-Linked Proteins/genetics* ; Gene Expression Regulation ; Genes, Reporter ; Green Fluorescent Proteins/metabolism* ; Litter Size ; Luminescent Proteins/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/metabolism* ; Reproduction/genetics* ; Signal Transduction ; Sperm Count ; Sperm Motility/genetics* ; Spermatozoa/metabolism* ; Uterus/metabolism*

Toxoplasmosis is a cosmopolitan zoonotic infection, caused by a unicellular protozoan parasite known as Toxoplasma gondii that belongs to the phylum Apicomplexa. It is estimated that over one-third of the world's population has been exposed and are latently infected with the parasite. In humans, toxoplasmosis is predominantly asymptomatic in immunocompetent persons, while among immunocompromised individuals may be cause severe and progressive complications with poor prognosis. Moreover, seronegative pregnant mothers are other risk groups for acquiring the infection. The life cycle of T. gondii is very complex, indicating the presence of a plurality of antigenic epitopes. Despite of great advances, recognize and construct novel vaccines for prevent and control of toxoplasmosis in both humans and animals is still remains a great challenge for researchers to select potential protein sequences as the ideal antigens. Notably, in several past years, constant efforts of researchers have made considerable advances to elucidate the different aspects of the cell and molecular biology of T. gondii mainly on microneme antigens, dense granule antigens, surface antigens, and rhoptry proteins (ROP). These attempts thereby provided great impetus to the present focus on vaccine development, according to the defined subcellular components of the parasite. Although, currently there is no commercial vaccine for use in humans. Among the main identified T. gondii antigens, ROPs appear as a putative vaccine candidate that are vital for invasion procedure as well as survival within host cells. Overall, it is estimated that they occupy about 1%–30% of the total parasite cell volume. In this review, we have summarized the recent progress of ROP-based vaccine development through various strategies from DNA vaccines, epitope or multi epitope-based vaccines, recombinant protein vaccines to vaccines based on live-attenuated vectors and prime-boost strategies in different mouse models.
Animals ; Antigens, Surface ; Apicomplexa ; Cell Size ; Epitopes ; Humans ; Immunization ; Life Cycle Stages ; Mice ; Molecular Biology ; Mothers ; Parasites ; Prognosis ; Toxoplasma* ; Toxoplasmosis ; Vaccines ; Vaccines, DNA ; Vaccines, Synthetic ; Zoonoses

Docetaxel-loaded nanomicelles were prepared in this study to improve the solubility and tumor targeting effect of docetaxel(DTX),and further evaluate their anticancer effects in vitro. PBAE-DTX nanomicelles were prepared by film-hydration method with amphiphilic block copolymer polyethyleneglycol methoxy-polylactide(PELA) and pH sensitive triblock copolymer polyethyleneglycol methoxy-polylactide-poly-β-aminoester(PBAE) were used respectively to prepare PELA-DTX nanomicelles and PBAE-DTX nanomicelles. The nanomicelles were characterized by physicochemical properties and the activity of mice Lewis lung cancer cells was studied. The results of particle size measurement showed that the blank micelles and drug-loaded micelles had similar particle sizes, ranging from 10 to 100 nm. The particle size of PBAE micelles was changed under weak acidic conditions, with good pH response. The encapsulation efficiency of the above two types of DTX-loaded nanomicelles determined by HPLC was(93.8±1.70)% and(87.2±4.10)%, and the drug loading amount was(5.3±0.10)% and(4.9±0.05)%,respectively. Furthermore,the DTX micelles also showed significant inhibitory effects on Lewis lung cancer cells by MTT assay, and pH-sensitive PBAE-DTX showed better cytotoxicity. The results of flow cytometry indicated that,the apoptosis rate of lung cancer Lewis cells was(20.72±1.47)%,(29.71±2.38)%,and(40.91±1.90)%(P<0.05) at 48 h after treatment in DTX,PELA-DTX,and PBAE-DTX groups. The results showed that different docetaxel preparations could promote the apoptosis of Lewis cells, and PBAE-DTX had stronger apoptotic-promoting effect. The pH-sensitive DTX-loaded micelles are promising candidates in developing stimuli triggered drug delivery systems in acidic tumor micro-environments with improved inhibitory effects of tumor growth on Lewis lung cancer.
Animals ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Docetaxel ; pharmacology ; Drug Carriers ; Lung Neoplasms ; drug therapy ; pathology ; Mice ; Micelles ; Nanoparticles ; Particle Size ; Taxoids

Na⁺/H⁺ exchangers (NHEs) have been shown to be involved in regulating cell volume and maintaining fluid and electrolyte homeostasis. Pooled evidences have suggested that loss of Na⁺/H⁺ exchanger isoform 8 (NHE8) impairs intestinal mucosa. Whether NHE8 participates in the pathology of infectious colitis is still unknown. Our previous study demonstrated that somatostatin (SST) could stimulate the expression of intestinal NHE8 so as to facilitate Na⁺ absorption under normal condition. This study further explored whether NHE8 participates in the pathological processes of infectious colitis and the effects of SST on intestinal NHE8 expression in the setting of infectious colitis. Our data showed that NHE8 expression was reduced in Citrobacter rodentium (CR) infected mice. Up-regulation of NHE8 improved diarrhea symptom and mucosal damage induced by CR. In vitro, a similar observation was also seen in Enteropathogenic E. coli (EPEC) infected Caco-2 cells. Seglitide, a SST receptor (SSTR) 2 agonist, partly reversed the inhibiting action of EPEC on NHE8 expression, but SSTR5 agonist (L-817,818) had no effect on the expression of NHE8. Moreover, SST blocked the phosphorylation of p38 in EPEC-infected Caco-2 cells. Taken together, these results suggest that enhancement of intestinal NHE8 expression by SST could ameliorate the symptoms of mice with infectious colitis.
Absorption ; Animals ; Anti-Inflammatory Agents ; Caco-2 Cells ; Cell Size ; Citrobacter rodentium ; Colitis* ; Diarrhea* ; Enteropathogenic Escherichia coli ; Homeostasis ; Humans ; In Vitro Techniques ; Intestinal Mucosa ; Mice* ; Pathologic Processes ; Pathology ; Phosphorylation ; Somatostatin* ; Up-Regulation*

PURPOSE: Wide-neck aneurysms (WNAs) associated with a dilated parent artery (PA) are not uncommon morphological abnormalities and usually cause inappropriate wall apposition and incomplete neck coverage of a tubular stent in stent-assisted coiling of aneurysms. We aimed to introduce a fusiform-shaped stent (FSS) and test its effectiveness in treating intracranial WNAs associated with a dilated PA using a three-dimensional (3D) model. MATERIALS AND METHODS: Two FSS types were designed with the middle one-third segment dilated by 10% (FSS10) and 20% (FSS20) and were compared with the tubular-shaped stent (TSS). A patient-specific 3D WNA model was prototyped and produced, and in vitro stent placement was performed. Angiographic images of the three stent types were analyzed and compared using predetermined parameters. RESULTS: The stent lumens were significantly larger in FSS10 and FSS20 than in TSS in the middle segments (P=0.046), particularly FSS20 (P=0.018). The non-covered area at the ostium tended to be smaller in FSS10 and FSS20 than in TSS, but the difference was not significant (P>0.05). The stent length was significantly longer in FSS10 and FSS20 than in TSS. The stent cell size was significantly larger in FSS than in TSS. CONCLUSION: Better vessel wall apposition and aneurysmal neck coverage was observed for FSS than for TSS. No significant difference was observed between FSS10 and FSS20.
Aneurysm ; Arteries ; Cell Size ; Endovascular Procedures ; Humans ; In Vitro Techniques* ; Intracranial Aneurysm* ; Neck ; Parents ; Stents*

OBJECTIVE: Pulmonary hypertension (PH) develops frequently in connective tissue diseases (CTD) and is an important prognostic factor. The aim of this study was to assess the prevalence of PH in patients with CTD by non-invasive echocardiography and analyze the potential biomarkers for helping to detect PH. METHODS: All Korean patients with CTD who had dyspnea on exertion or interstitial lung disease (ILD) were screened for PH with echocardiography and clinical data were collected from four hospitals. RESULTS: Among 196 patients with CTD, 108 (55.1%) had ILD and 21 had PH defined as >40 mmHg. Of the 21 patients with PH, 10, 4, and 3 patients had systemic sclerosis, systemic lupus erythematosus, and mixed connective tissue disease, respectively. There was no difference in the incidence of PH according to the presence of ILD; 12 patients (11.1%) with ILD had PH and 9 patients (10.2%) without ILD had PH. The results of the pulmonary function test, total cholesterol, red cell volume distribution width, alkaline phosphatase, and the New York Heart Association (NYHA) functional class III or IV differed significantly according to the presence of PH. In multiple regression analysis, NYHA functional class III or IV (odd ratio [OR]=7.3, p=0.009) and forced vital capacity (OR=0.97, p=0.043) were independent predictive factors of PH. CONCLUSION: PH is not associated with the presence of ILD in Korean patients with CTD. On the other hand, NYHA functional class III or IV and decreased forced vital capacity indicate the presence of PH in connective tissue disease.
Alkaline Phosphatase ; Biomarkers ; Cell Size ; Cholesterol ; Connective Tissue Diseases* ; Connective Tissue* ; Dyspnea ; Echocardiography ; Hand ; Heart* ; Humans ; Hydrogen-Ion Concentration ; Hypertension, Pulmonary* ; Incidence ; Lung Diseases, Interstitial* ; Lupus Erythematosus, Systemic ; Mixed Connective Tissue Disease ; Prevalence ; Respiratory Function Tests ; Risk Factors ; Scleroderma, Systemic ; Vital Capacity*

The therapeutic application of deoxypodophyllotoxin (DPT) is limited due to its poor water solubility and stability. In the present study, the micelles assembled by the amphiphilic block copolymers (mPEG-PDLLA) were constructed to improve the solubility and safety of DPT for their in vitro and in vivo application. The central composite design was utilized to develop the optimal formulation composed of 1221.41 mg mPEG-PDLLA, the weight ratio of 1 : 4 (mPEG-PDLLA : DPT), 30 mL hydration volume and the hydration temperature at 40 °C. The results showed that the micelles exhibited uniformly spherical shape with the diameter of 20 nm. The drug-loading and entrapment efficiency of deoxypodophyllotoxin-polymeric micelles (DPT-PM) were about (20 ± 2.84)% and (98 ± 0.79)%, respectively, indicating that the mathematical models predicted well for the results. Compared to the free DPT, the cytotoxicity showed that blank micelles possessed great safety for Hela cells. In addition, the DPT loaded micelle formulation achieved stronger cytotoxicity at the concentration of 1 × 10 mol·L, which showed significant difference from free DPT (P < 0.05). In conclusion, the micelles were highly promising nano-carriers for the anti-tumor therapy with DPT.
Antineoplastic Agents ; chemistry ; toxicity ; Cell Survival ; drug effects ; Drug Carriers ; chemistry ; Drug Delivery Systems ; methods ; Drug Design ; HeLa Cells ; Humans ; Micelles ; Particle Size ; Podophyllotoxin ; analogs & derivatives ; chemistry ; toxicity ; Polyesters ; chemistry ; Polyethylene Glycols ; chemistry ; Solubility ; Surface Properties

OBJECTIVE: To establish a model for predicting the short-term prognosis of patients with HBV-related acute-onchronic liver failure (HBV-ACLF) based on red blood cell distribution width (RDW) and the model for end-stage liver disease (MELD) scores. METHODS: A total of 245 patients with HBV-ACLF were retrospectively analyzed for their clinical data and results of routine hematological tests, liver function, renal function, coagulation test, HBV-DNA, and other indicators at admission. Univariate analysis and binary logistic regression analysis were used to test the short-term risk factors for death of the patients, and the MELD-RDW model was established. The accuracy of each index and the established model was verified using the ROC curve. RESULTS: The surviving patients with HBV-ACLF had significantly decreased RDW (14.97 ± 1.38) and MELD score (23.54±4.35) compared with those in the patients dead within 90 days (17.05±2.92 and 28.95±5.99, respectively). Multivariate analysis indicated that RDW was a significant independent prognostic factor for mortality in patients with HBVACLF (OR=1.840, 95%CI: 1.47902.289, < 0.005). The risk assessment model was [logisticMELD-RDW]=-9.375+0.582×RDW- 0.091×ALB-0.05×PTA+0.186×MELD. The area under the ROC curve of MELD score combined with RDW was 0.878, which was higher than RDW (0.724) and MELD score (0.780) alone. CONCLUSIONS RDW is an independent prognostic indicator for mortality in patients with HBV-ACLF. Compared with MELD score, the risk assessment model based on MELD and RDW has a greater value in predicting the short-term prognosis of patients with HBV-ACLF.
Acute-On-Chronic Liver Failure ; blood ; mortality ; Cell Size ; End Stage Liver Disease ; blood ; mortality ; Erythrocyte Volume ; Erythrocytes ; cytology ; Hepatitis B ; blood ; complications ; mortality ; Humans ; Prognosis ; ROC Curve ; Retrospective Studies