Altered expression of the Plexin-B2 system in tuberous sclerosis complex and focal cortical dysplasia IIb lesions.

Tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type IIb are the predominant causes of drug-refractory epilepsy in children. Dysmorphic neurons (DNs), giant cells (GCs), and balloon cells (BCs) are the most typical pathogenic profiles in cortical lesions of TSC and FCD IIb patients. However, mechanisms underlying the pathological processes of TSC and FCD IIb remain obscure. The Plexin-B2-Sema4C signalling pathway plays critical roles in neuronal morphogenesis and corticogenesis during the development of the central nervous system. However, the role of the Plexin-B2 system in the pathogenic process of TSC and FCD IIb has not been identified. In the present study, we investigated the expression and cell distribution characteristics of Plexin-B2 and Sema4C in TSC and FCD IIb lesions with molecular technologies. Our results showed that the mRNA and protein levels of Plexin-B2 expression were significantly increased both in TSC and FCD IIb lesions versus that in the control cortex. Notably, Plexin-B2 was also predominantly observed in GCs in TSC epileptic lesions and BCs in FCD IIb lesions. In contrast, the expression of Sema4C, the ligand of Plexin-B2, was significantly decreased in DNs, GCs, and BCs in TSC and FCD IIb epileptic lesions. Additionally, Plexin-B2 and Sema4C were expressed in astrocytes and microglia cells in TSC and FCD IIb lesions. Furthermore, the expression of Plexin-B2 was positively correlated with seizure frequency in TSC and FCD IIb patients. In conclusion, our results showed the Plexin-B2-Sema4C system was abnormally expressed in cortical lesions of TSC and FCD IIb patients, signifying that the Plexin-B2-Sema4C system may play a role in the pathogenic development of TSC and FCD IIb.

NetAUC: A network-based multi-biomarker identification method by AUC optimization.

Complex diseases are caused by a variety of factors, and their diagnosis, treatment and prognosis are usually difficult. Proteins play an indispensable role in living organisms and perform specific biological functions by interacting with other proteins or biomolecules, their dysfunction may lead to diseases, it is a natural way to mine disease-related biomarkers from protein-protein interaction network. AUC, the area under the receiver operating characteristics (ROC) curve, is regarded as a gold standard to evaluate the effectiveness of a binary classifier, which measures the classification ability of an algorithm under arbitrary distribution or any misclassification cost. In this study, we have proposed a network-based multi-biomarker identification method by AUC optimization (NetAUC), which integrates gene expression and the network information to identify biomarkers for the complex disease analysis. The main purpose is to optimize two objectives simultaneously: maximizing AUC and minimizing the number of selected features. We have applied NetAUC to two types of disease analysis: 1) prognosis of breast cancer, 2) classification of similar diseases. The results show that NetAUC can identify a small panel of disease-related biomarkers which have the powerful classification ability and the functional interpretability.

Effect of telehealth intervention on breast cancer patients' quality of life and psychological outcomes: A meta-analysis.

Introduction Telehealth intervention has been proposed as an innovative intervention approach to breast cancer patients, but there are still conflicting results in the literature about its effect. Methods PubMed, EMBASE, CENTRAL and China National Knowledge Infrastructure (CNKI) were searched from inception to 3 October 2016 for randomized controlled trials (RCTs) which assessed the effect of telehealth intervention versus usual care in breast cancer patients. No language restrictions were used. Standardized mean difference (SMD) with corresponding 95% confidence interval (95% CI) was pooled when needed. Subgroup and sensitivity analyses were conducted if necessary and feasible. Results Twenty RCTs with a total of 2190 participants were included into this meta-analysis. Compared with usual care, telehealth intervention was associated with higher quality of life (SMD = 0.60, 95% CI 0.18-1.01, p = 0.005) and self-efficacy (SMD = 0.59, 95% CI 0.19-0.98, p = 0.003), with less depression (SMD = -1.29, 95% CI -2.28 to -0.30, p = 0.01), distress (SMD = -0.25, 95% CI -0.40 to -0.10, p = 0.001) and perceived stress (SMD = -0.30, 95% CI, -0.59 to -0.02, p = 0.04). However, anxiety score did not differ significantly between the two groups (SMD = -0.09, 95% CI -0.22 to 0.04, p = 0.17). Discussion Telehealth intervention is superior to usual care in breast cancer patients for improved quality of life, higher self-efficacy and less depression, distress, and perceived stress. However, these results should be recognized cautiously due to between-study heterogeneity, indicating that further well-designed RCTs are warranted.

Aqueous proinflammatory cytokines in acute primary angle-closure eyes.

AIM: To evaluate changes of proinflammatory cytokines in aqueous humor of patients with acute primary angle-closure (APAC) and age-related cataracts. METHODS: Twenty eyes of 20 APAC patients and 15 eyes of 15 age-related cataract patients were included in this cross-sectional study. Aqueous humor samples were collected prospectively. The levels of 20 proinflammatory cytokines were evaluated in the aqueous humor of the APAC and cataract patients using the multiplex bead immunoassay technique. Clinical data were collected for correlation analysis. RESULTS: Seven of the 20 proinflammatory cytokines included in the magnetic bead panel were detectable in both APAC eyes and cataract eyes: interleukin (IL)-10, IL-12, IL-15, IL-21, IL-6, chemokine (C-C motif) ligand 20, and tumor necrosis factor alpha (TNF-α). IL-27 was only detectable in APAC eyes. Compared with the cataract eyes, the APAC eyes had significantly elevated concentrations of IL-12 (P=0.036), IL-15 (P=0.001), IL-6 (P=0.012), and IL-27 (only detectable in APAC eyes). Age was positively correlated with IL-12 (P=0.022) and IL-6 (P=0.037), and time elapsed between APAC onset and aqueous humor samples collection was positively correlated with IL-15 (P=0.037), IL-27 (P=0.040), and TNF-α (P=0.042). CONCLUSION: Several proinflammatory cytokines including IL-12, IL-15, IL-6 and IL-27, were elevated in the APAC eyes and may be implicated in its pathologic mechanism.

Adjunctive with versus without intravitreal bevacizumab injection before Ahmed glaucoma valve implantation in the treatment of neovascular glaucoma.

BACKGROUND: Neovascular glaucoma (NVG) is a refractory disease which is difficult to manage. This study aimed at evaluating the efficacy and safety of adjunctive intravitreal bevacizumab (IVB) injection in conjunction with Ahmed glaucoma valve implantation (AGVI) in the management of NVG. METHODS: This was a retrospective study of patients with NVG in whom AGVI was performed between October 2008 and May 2012. The sample was divided into two groups according to the pretreatment: with adjunctive IVB injection (the IVB group, n = 25 eyes) and without adjunctive IVB injection (the control group, n = 28 eyes). The surgical success rate, number of antiglaucoma medications used, best-corrected visual acuity (BCVA), postoperative complications, regression, and recurrence of iris neovascularization (NVI) were analyzed between the groups. RESULTS: The surgical outcomes of the two groups were compared. The complete success rates in the IVB and control groups were 84.0% and 64.3% at 12 months and 80.0% and 53.6% at 18 months, respectively. There was a significant difference between the two groups (P = 0.041). Mean postoperative intraocular pressures, mean number of postoperative antiglaucoma medications, and BCVA were not significant between the two groups. The NVI in 22 (88.0%) eyes had completely regressed within 2 - 8 days after IVB. However, NVI recurred in 10 eyes (40.0%) 2 - 9 months later after IVB. The IVB group had only 1 case (4.0%) of hyphema out of 25 eyes, while there were 8 (28.6%) cases of hyphema out of 28 eyes in the control group (P = 0.026). CONCLUSIONS: This study showed that preoperative IVB injection reduced NVI remarkably, decreased hyphema, and led to higher surgical success rates. Pre-operative IVB injection may be an effective adjunct to AGVI in the management of NVG.

Anti-tumor activity of N-trimethyl chitosan-encapsulated camptothecin in a mouse melanoma model.

BACKGROUND: Camptothecin (CPT) has recently attracted increasing attention as a promising anticancer agent for a variety of tumors. But the clinical application is largely hampered by its extreme water insolubility and unpredictable side effect. It is essential to establish an efficient and safe protocol for the administration of CPT versus melanoma. METHODS: Camptothecin was encapsulated with N-trimethyl chitosan (CPT-TMC) through microprecipitation and sonication. Its inhibition effect on B16-F10 cell proliferation and induction of apoptosis was evaluated by MTT assay and flow cytometric analysis in vitro. The anti-tumor activity of CPT-TMC was evaluated in C57BL/6 mice bearing B16-F10 melanoma. Tumor volume, tumor weight and survival time were recorded. Assessment of apoptotic cells within tumor tissue was performed by TUNEL assay. Antiangiogenesis and antiproliferation effects of CPT-TMC in vivo were conducted via CD31 and PCNA immunohistochemistry, respectively. RESULTS: CPT-TMC efficiently inhibited B16-F10 cells proliferation and increased apoptosis in vitro. Experiment group showed significant inhibition compared with free CPT-treated group (81.3% vs. 56.9%) in the growth of B16-F10 melanoma xenografts and prolonged the survival time of the treated mice (P < 0.05). Decreased cell proliferation, increased tumor apoptosis as well as a reduction in angiogenesis were observed. CONCLUSIONS: Our data suggest that N-trimethyl chitosan-encapsulated camptothecin is superior to free CPT by overcoming its insolubility and finally raises the potential of its application in melanoma therapy.

Preparation and characterization of magnetic poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) microspheres.

In this article, nano-magnetite particles (ferrofluid, Fe3O4) were prepared by chemical co-deposition method. A series of biodegradable triblock poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) copolymers were synthesized by ring-opening polymerization method from epsilon-caprolactone (epsilon-CL) initiated by poly(ethylene glycol) diol (PEG) using stannous octoate as catalyst. And the magnetic PCEC composite microspheres were prepared by solvent diffusion method. The properties of the ferrofluid, PCEC copolymer, and magnetic PCEC microspheres were studied in detail by SEM, VSM, XRD, Malvern Laser Particle Sizer, 1H-NMR, GPC, and TG/DTG. Effects of macromolecular weight and concentration of polymer, and the time for ultrasound dispersion on properties of magnetic microspheres were also investigated. The obtained magnetic PCEC microspheres might have great potential application in targeted drug delivery system or cell separation.

Synthesis, characterization, and hydrolytic degradation behavior of a novel biodegradable pH-sensitive hydrogel based on polycaprolactone, methacrylic acid, and poly(ethylene glycol).

In this work, a new kind of biodegradable pH-sensitive hydrogel was successfully synthesized by UV-initiated free radical polymerization. The obtained hydrogel was characterized by (1)H NMR and FTIR. Swelling behavior in different aqueous media and pH responsivity of the hydrogels were studied in detail as well. With increase in pH from 1.2 to 7.2, swelling ratio of the hydrogel increased. The morphology was observed by scanning electron microscopy, and the hydrolytic degradation behavior was also investigated in this work.

One-step preparation of poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) nanoparticles for plasmid DNA delivery.

In this article, a kind of biodegradable poly(epsilon-caprolactone)-Poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) copolymer was synthesized by ring-opening polymerization method. The PCEC nanoparticles were prepared at one-step by modified emulsion solvent evaporation method using CTAB as stabilizer. With increase in PCEC concentration, the particle size increased obviously, but zeta potential only increased slightly. The obtained cationic PCEC nanoparticle was employed to condense and adsorb DNA onto its surface. Plasmid GFP (pGFP) was used as model plasmid to evaluate the loading capacity of cationic PCEC nanoparticles in this work. The DNA/nanoparticles weight ratio at 1:16 induced almost neutral zeta potential of DNA-nanoparticles complex. At this time, the size of complex became abnormally large which implied aggregates formed. So DNA-nanoparticles weight ratio should be chosen carefully. The cationic PCEC nanoparticles had the capacity of condensing plasmid DNA into complex when the DNA/nanoparticles weight ratio was lower than 1:8, which was evidenced by gel retardation assay. In vitro release behavior of DNA/nanoparticle complexes was also studied here. The obtained cationic PCEC nanoparticles might have great potential application in DNA delivery.

[Inhibition of HBs-GFP fusion gene expression by RNA interference].

OBJECTIVE: To develop an effective report gene system to test the effect of small interfering RNA (siRNA). METHODS: HBV S gene was fused with enhanced green fluorescent protein (EGFP) gene to form HBs-GFP and the plasmid containing HBs-GFP was constructed. A vector expressing small hairpin RNA (shRNA) pAVU6 + 4sh357 was also constructed. Two plasmids were co-transfected into HepG2 cells transiently. The fluorescence of HBs-GFP was detected by fluorescence-activated cell sorting (FACS). The mRNA expression in HepG2 cells was detected by conventional RT-PCR and real-time PCR. RESULTS: siRNA inhibited the expression of HBs-GFP 72 hours post transfection. The fluorescence of HBs-GFP in HepG2 cells treated with pAVU6+4sh357 was reduced by 55.4% compared with that of controls. The HBs-GFP expression in HepG2 cells treated with pAVU6+4sh357 was reduced by 76.3% and 90% as measured with conventional RT-PCR and real-time PCR, respectively. CONCLUSION: This investigation demonstrated siRNA derived from shRNA expression vectors can inhibit the expression of HBs-GFP in HepG2 cells.