Xingguo Zhang

Tribological properties of carbon-nanotube-reinforced copper composites

Tribological properties of carbon-nanotube-reinforced copper composites were investigated using a pin-on-disk test rig under dry conditions. The composites containing 4–16 vol% carbon nanotubes (CNTs) were fabricated by a powder-metallurgy technique. The tests were carried out at normal loads between 10 and 50 N, and the effect of volume fraction of CNTs on tribological behavior of the composites was examined. The composites revealed a low coefficient of friction compared with the copper matrix alloy. Due to the effects of the reinforcement and reduced friction, the wear rate of the composites decreased with increasing volume fraction of CNTs at low and intermediate loads. The composites with a high volume fraction of CNTs exhibited high porosity and their wear resistance decreased under high-load conditions.

Epirubicin‐Loaded Superparamagnetic Iron‐Oxide Nanoparticles for Transdermal Delivery: Cancer Therapy by Circumventing the Skin Barrier

The transdermal administration of chemotherapeutic agents is a persistent challenge for tumor treatments. A model anticancer agent, epirubicin (EPI), is attached to functionalized superparamagnetic iron-oxide nanoparticles (SPION). The covalent modification of the SPION results in EPI-SPION, a potential drug delivery vector that uses magnetism for the targeted transdermal chemotherapy of skin tumors. The spherical EPI-SPION composite exhibits excellent magnetic responsiveness with a saturation magnetization intensity of 77.8 emu g(-1) . They feature specific pH-sensitive drug release, targeting the acidic microenvironment typical in common tumor tissues or endosomes/lysosomes. Cellular uptake studies using human keratinocyte HaCaT cells and melanoma WM266 cells demonstrate that SPION have good biocompatibility. After conjugation with EPI, the nanoparticles can inhibit WM266 cell proliferation; its inhibitory effect on tumor proliferation is determined to be dose-dependent. In vitro transdermal studies demonstrate that the EPI-SPION composites can penetrate deep inside the skin driven by an external magnetic field. The magnetic-field-assisted SPION transdermal vector can circumvent the stratum corneum via follicular pathways. The study indicates the potential of a SPION-based vector for feasible transdermal therapy of skin cancer.

Ginsenoside Rg1 exerts a protective effect against Aβ₂₅₋₃₅-induced toxicity in primary cultured rat cortical neurons through the NF-κB/NO pathway.

Ginsenoside Rg1 (Rg1) is a multipotent triterpene saponin extracted from ginseng, and has been proven to act as a nootropic agent against various types of neurological damage. The present study was designed to investigate the neuroprotective effect and the underlying mechanisms of Rg1 on apoptosis induced by β-amyloid peptide 25-35 (Aβ25-35) in primary cultured cortical neurons. The primary neurons were preincubated with 20 µM Rg1 for 24 h and exposed to 10 µM Aβ25-35 for 72 h. In the present study, we found that Rg1 prevented nuclear factor κ-light-chain‑enhancer of activated B cells (NF-κB) nuclear translocation and IκB-α phosphorylation in primary cultured cortical neurons after Aβ25-35 exposure by scavenging excess reactive oxygen species (ROS); ROS was measured using DCFDA and examined using a fluorescence microscope. In addition, Rg1 successfully suppressed Aβ25‑35-inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in a NF-κB-dependent manner; the suppression of NO was clearly illustrated by the NO production assay. Pretreatment of the cells with Rg1 elevated the proportion of Bcl-2/Bax, lessened the release of cytochrome c from mitochondria into cytoplasm and then blocked mitochondrial apoptotic cascades after Aβ25-35 insult by lowering NO generation. Taken together, our data demonstrate that Rg1 rescues primary cultured cortical neurons from Aβ25-35-induced cell apoptosis through the downregulation of the NF-κB/NO signaling pathway.

Analytical methods for brain targeted delivery system in vivo: Perspectives on imaging modalities and microdialysis

Since the introduction of microdialysis in 1974, the semi-invasive analytical method has grown exponentially. Microdialysis is one of the most potential analysis technologies of pharmacological drug delivery to the brain. In recent decades, analysis of chemicals targeting the brain has led to many improvements. It seems likely that fluorescence imaging was limited to ex vivo and in vitro applications with the exception of several intravital microscopy and photographic imaging approaches. X-ray computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) have been commonly utilized for visualization of distribution and therapeutic effects of drugs. The efficient analytical methods for studies of brain-targeting delivery system is a major challenge in detecting the disposition as well as the variances of the factors that regulate the substances delivery into the brain. In this review, we highlight some of the ongoing trends in imaging modalities and the most recent developments in the field of microdialysis of live animals and present insights into exploiting brain disease for therapeutic and diagnostics purpose.

The Efficacy and Safety of Leflunomide for the Treatment of Lupus Nephritis in Chinese Patients: Systematic Review and Meta-Analysis

Objective To evaluate the clinical efficacy and safety of leflunomide as a new immunosuppressive medicine in lupus nephritis (LN) through a meta-analysis. Methods A systematic review evaluating the efficacy and safety of leflunomide compared with cyclophosphamide in adult patients with LN was performed. Data from relevant randomized controlled trials (RCTs) performed before December 2014 was collected from several databases (PubMed, Embase, Cochrane Library, CNKI and CBM). No language restrictions were applied. Efficacy outcomes included overall remission, SLE Disease Activity Index (SLEDAI) score, 24-hour proteinuria and serum creatinine. Safety data were analyzed. The effects of treatment on these outcomes were summarized as relative risks (RRs) with 95% confidence intervals (CIs) and mean differences were pooled using a fixed or random effects model. Results Eleven RCTs with Jadad score of 3 or greater were identified and included a total of 254 patients. Cyclophosphamide was served as the control drug in all trials. The SLEDAI score, urine protein level and serum creatinine decreased significantly following leflunomide treatment (P<0.05). Leflunomide was superior to cyclophosphamide in achieving complete and total remission, but no difference in SLEDAI score was found between these two treatments (P>0.05). Additionally, patients receiving leflunomide treatment showed favorable renal function profiles, especially regarding the 24-hour proteinuria (mean difference: -0.58, 95%CI: -0.78~-0.37, P<0.01) and serum creatinine (mean difference: -0.20, 95%CI: -0.39~-0.01, P<0.05). In the safety comparison, leflunomide was safer than cyclophosphamide regarding adverse drug reactions (ADRs), including liver damage (RR = 0.53, 95%CI: 0.33~0.87, P<0.05), alopecia (RR = 0.38, 95%CI: 0.17~0.85, P<0.05), leukopenia (RR = 0.25, 95%CI: 0.08~0.77, P<0.05) and infection (RR = 0.54, 95%CI: 0.32~0.92, P<0.05), without increased risk of gastrointestinal reaction, rash or herpes zoster infection. Conclusions Leflunomide is a promising therapy for LN treatment, primarily because of the comparable efficacy and favorable safety profile determined by this meta-analysis of RCTs. Larger RCTs with longer duration of observation are necessary to provide strong evidence of the efficacy and safety of leflunomide in LN patients.

The Effect of ABCB1 C3435T Polymorphism on Cyclosporine Dose Requirements in Kidney Transplant Recipients: A Meta-Analysis.

Cyclosporine A (CsA) is a substrate of the multi‐drug efflux pump P‐glycoprotein (P‐gp) encoded by ABCB1. Among the various single nucleotide polymorphisms (SNPs) of ABCB1, C3435T has been extensively investigated to determine the relationship with the pharmacokinetics of CsA. However, the results are controversial. This meta‐analysis was designed to evaluate the influence of C3435T SNP on the dose‐adjusted trough (C0/D) and peak (Cmax/D) concentrations of CsA. Based on a literature search of four authoritative databases, 13 studies since 2001 concerning 1293 kidney transplant recipients were included. The results indicated a significant difference of C0/D and Cmax/D between 3435CC and 3435TT genotype carriers (weighted mean difference (WMD) of C0/D: 4.18 (ng ml−1)/(mg kg−1), 95% CIs: 1.00–7.37, p = 0.01; WMD of Cmax/D: 20.85 (ng ml−1)/(mg kg−1), 95% CIs: 2.25–39.46, p = 0.03). Subgroup analysis by ethnicity demonstrated that C0/D was lower in Asian CC versus TT genotype carriers (WMD = 10.32 (ng ml−1)/(mg kg−1), 95% CIs: 4.78–15.85, p = 0.0003) but did not vary by genotype for Caucasian recipients. Moreover, significant variation of C0/D was found at 1 week and 1–3 months after transplantation between CC and TT genotype carriers. Therefore, this meta‐analysis showed a correlation between ABCB1 C3435T polymorphism and the dose‐adjusted concentration of CsA. Patients with 3435CC genotype will require a higher dose of CsA to achieve target therapeutic concentrations when compared with 3435TT carriers after kidney transplantation, especially in the Asian population and especially during the early and middle time periods after transplantation.

Cerebral microdialysis in glioma studies, from theory to application

Despite recent advances in the treatment of solid tumors, there are few effective treatments for malignant gliomas due to the infiltrative nature, and the protective shield of blood-brain barrier or blood-tumor barriers that restrict the passage of chemotherapy drugs into the brain. Imaging techniques, such as PET and MRI, have allowed the assessment of tumor function in vivo, but they are indirect measures of activity and do not easily allow continuous repeated evaluations. Because the biology of glioma on a cellular and molecular level is fairly unknown, especially in relation to various treatments, the development of novel therapeutic approaches to this devastating condition requires a strong need for a deeper understanding of the tumors pathophysiology and biochemistry. Cerebral microdialysis, a probe-based sampling technique, allows a discrete volume of the brain to be sampled for neurochemical analysis of neurotransmitters, metabolites, biomarkers, and chemotherapy drugs, which has been employed in studying brain tumors, and is significant for improving the treatment of glioma. In this review, the current concepts of cerebral microdialysis for glioma are elucidated, with a special emphasis on its application to neurochemistry and pharmacokinetic studies.

Brain pharmacokinetics of neurotoxin-loaded PLA nanoparticles modified with chitosan after intranasal administration in awake rats.

Context: Neurotoxin (NT), an analgesic peptide which was separated from the venom of Naja naja atra, is endowed an exceptional specificity of action that blocks transmission of the nerve impulse by binding to the acetylcholine receptor in the membrane. However, it has limited permeability across the blood-brain barrier (BBB). Objective: The purpose of this study was to encapsulate NT within polylactic acid (PLA) nanoparticles (NPs) modified with chitosan (NT-PLA-cNPs) and to evaluate their brain pharmacokinetic behaviors after intranasal (i.n.) administration using a microdialysis technique in free-moving rats. Methods: NT-PLA-cNPs (NT labeled with fluorescein isothiocyanate) were prepared and characterized. Then, NT-PLA-cNPs were i.n. administered to rats and the fluorescence intensity in the periaqueductal gray (PAG) was monitored for up to 480 min, with NT-PLA-NPs and NT solution as control groups. Results: The NPs prepared were spherical with a homogenous size distribution. The mean particle size, zeta potential, and entrapment efficiency were 140.5 ± 5.4 nm, +33.71 ± 3.24 mV, and 83.51 ± 2.65%, respectively. The brain transport results showed that Tmax of NT-PLA-cNPs was equal with that of NT-PLA-NPs after i.n. administration (150 min). The Cmax and AUC0–8 h of each group followed the following order: NT-PLA-cNPs > NT-PLA-NPs. The corresponding absolute bioavailability (Fabs) of NT-PLA-cNPs was about 151% with NT-PLA-NPs as reference preparations. Conclusion: These results suggest that NPs modified with chitosan have better brain targeting efficiency and are a promising approach for i.n. delivery of large hydrophilic peptides and proteins in improving the treatment of central nervous system (CNS) disorders.