Mitofusin 2 inhibits high glucose-induced apoptosis of human lens epithelial cells via modulating mitochondrial function and autophagy.

INTRODUCTION: Diabetic cataract (DC) is a common ocular complication of diabetes. Mitofusin 2 (MFN2), a mitochondrial fusion protein, is involved in the pathogenesis of cataract and diabetic complications. However, its role and molecular mechanisms in DC remain unclear. MATERIALS AND METHODS: DC models in rats were induced by intraperitoneal injection of streptozocin (STZ) for 12 weeks. We measured the body weight of rats, blood glucose concentrations, sorbitol dehydrogenase (SDH) activity and advanced glycation end products (AGE) content in the lenses of rats. MFN2 mRNA and protein expression levels in the lenses were detected by RT-qPCR and western blot assays. In vitro, human lens epithelial (HLE) B3 cells were treated for 48 h with 25 mM glucose (high glucose, HG) to induce cell damage. To determine the role of MFN2 in HG-induced cell damage, HLE-B3 cells were transfected with lentivirus loaded with MFN2 overexpression plasmid or short hairpin RNA (shRNA) to overexpress or knock down MFN2 expression, followed by HG exposure. Cell viability was assessed by CCK-8 assay. Flow cytometry was used to detect cell apoptosis and reactive oxygen species (ROS) level. JC-1 staining showed the changes in mitochondrial membrane potential (Δψm). The mediators related to apoptosis, mitochondrial damage, and autophagy were determined. RESULTS: STZ-administrated rats showed reduced body weight, increased blood glucose levels, elevated SDH activity and AGE content, suggesting successful establishment of the DC rat model. Interestingly, MFN2 expression was significantly downregulated in DC rat lens and HG-induced HLE-B3 cells. Further analysis showed that under HG conditions, MFN2 overexpression enhanced cell viability and inhibited apoptosis accompanied by decreased Bax, cleaved caspase-9 and increased Bcl-2 expression in HLE-B3 cells. MFN2 overexpression also suppressed the mitochondrial damage elicited by HG as manifested by reduced ROS production, recovered Δψm and increased mitochondrial cytochrome c (Cyto c) level. Moreover, MFN2 overexpression increased LC3BⅡ/LC3BⅠ ratio and Beclin-1 expression, but decreased p62 level, and blocked the phosphorylation of mTOR in HG-treated HLE-B3 cells. In contrast, MFN2 silencing exerted opposite effects. CONCLUSIONS: Our findings indicate that MFN2 expression may be essential for preventing lens epithelial cell apoptosis during development of diabetic cataract.

Ultralight Flexible Collagen Fiber Based Aerogels Derived from Leather Solid Waste for High Electromagnetic Interference Shielding.

Designing and developing high-performance shielding materials against electromagnetic interference is of utmost importance due to the rapid advancement of wireless telecommunication technologies. Such materials hold both fundamental and technological significance. A three-stage process is presented for creating ultralight, flexible aerogels from biomass to shield against electromagnetic interference. Collagen fibers sourced from leather solid waste are used for: (i) freeze-drying preparation of collagen fibers/poly(vinyl alcohol) (PVA) aerogels, (ii) adsorption of silver nanowires (AgNWs) onto collagen fiber/PVA aerogels, and (iii) Hydrophobic modification of collagen fiber/PVA/AgNWs aerogels with 1H, 1H, 2H, 2H-perfluorodecyltriethoxysilane (POTS). Scanning electron microscopy studies reveal that an interweaving of AgNWs and collagen fiber/PVA porous network has formed a conductive network, exhibiting an electrical conductivity of 103 S·m-1. The electromagnetic interference shielding effectiveness reached more than 62 dB, while the density was merely 5.8 mg/cm3. The collagen fiber/PVA/AgNWs/POTS aerogel displayed an even better electromagnetic shielding efficiency of 73 dB and water contact angle of 147°. The study results emphasize the distinctive capacity of leather solid waste to generate cost-effective, ecofriendly, and highly efficient electromagnetic interference shielding materials.

Medial Protrusio Technique Versus Structural Autologous Bone-Grafting Technique in Total Hip Arthroplasty for Crowe Type II to III Hip Dysplasia.

BACKGROUND: It is unclear whether acetabular reconstruction techniques have any impact on clinical outcomes. This study aimed to determine (1) whether acetabular reconstruction techniques influenced the position of the acetabular cup and (2) whether clinical outcomes based on the acetabular reconstruction techniques differ in patients undergoing total hip arthroplasty (THA) with Crowe II to III developmental dysplasia of the hip. METHODS: This was a retrospective analysis of prospectively collected data from 69 patients (74 hips) who were treated with cementless THA using medial protrusio technique (MPT) or structural autologous bone-grafting technique (SABT). There were 39 patients (41 hips) included in the MPT group and 30 patients (33 hips) in the SABT group. Clinical and radiographic outcomes were evaluated. RESULTS: All patients were followed up for at least 3 years. There were similar results between the 2 groups in terms of blood loss, Harris hip score, leg length discrepancy, cup inclination, cup anteversion, and proportion of cup coverage (P > .05). The operative time was significantly longer in the SABT group compared with the MPT group (P < .001). The postoperative vertical center of rotation was significantly higher in the MPT group compared with the SABT group (P = .001), and postoperative horizontal center of rotation was significantly shallower in the SABT group compared with the MPT group (P < .001). CONCLUSION: The MPT and SABT provide similar clinical and radiographic outcomes in the management of Crowe II to III developmental dysplasia of the hip by cementless THA. However, the MPT has the advantage of a shorter operative time, whereas the SABT is more conducive to placing the acetabular cup in an anatomic position. LEVEL OF EVIDENCE: Level III, Therapeutic, Case-Control Study.

Anti-tumor effects of novel alkannin derivatives with potent selectivity on comprehensive analysis.

BACKGROUND: Therapeutic approaches based on glycolysis and energy metabolism of tumor cells are new promising strategies for the treatment of cancer. Currently, researches on the inhibition of pyruvate kinase M2, a key rate limiting enzyme in glycolysis, have been corroborated as an effective cancer therapy. Alkannin is a potent pyruvate kinase M2 inhibitor. However, its non-selective cytotoxicity has affected its subsequent clinical application. Thus, it needs to be structurally modified to develop novel derivatives with high selectivity. PURPOSE: Our study aimed to ameliorate the toxicity of alkannin through structural modification and elucidate the mechanism of the superior derivative 23 in lung cancer therapy. METHODS: On the basis of the principle of collocation, different amino acids and oxygen-containing heterocycles were introduced into the hydroxyl group of the alkannin side chain. We examined the cell viability of all derivatives on three tumor cells (HepG2, A549 and HCT116) and two normal cells (L02 and MDCK) by MTT assay. Besides, the effect of derivative 23 on the morphology of A549 cells as observed by Giemsa and DAPI staining, respectively. Flow cytometry was performed to assess the effects of derivative 23 on apoptosis and cell cycle arrest. To further assess the effect of derivative 23 on the Pyruvate kinase M2 in glycolysis, an enzyme activity assay and western blot assay were performed. Finally, in vivo the antitumor activity and safety of the derivative 23 were evaluated by using Lewis mouse lung cancer xenograft model. RESULTS: Twenty-three novel alkannin derivatives were designed and synthesized to improve the cytotoxicity selectivity. Among these derivatives, derivative 23 showed the highest cytotoxicity selectivity between cancer and normal cells. The anti-proliferative activity of derivative 23 on A549 cells (IC50 = 1.67 ± 0.34 µM) was 10-fold higher than L02 cells (IC50 = 16.77 ± 1.44 µM) and 5-fold higher than MDCK cells (IC50 = 9.23 ± 0.29 µM) respectively. Subsequently, fluorescent staining and flow cytometric analysis showed that derivative 23 was able to induce apoptosis of A549 cells and arrest the cell cycle in the G0/G1 phase. In addition, the mechanistic studies suggested derivative 23 was an inhibitor of pyruvate kinase; it could regulate glycolysis by inhibiting the activation of the phosphorylation of PKM2/STAT3 signaling pathway. Furthermore, studies in vivo demonstrated derivative 23 significantly inhibited the growth of xenograft tumor. CONCLUSION: In this study, alkannin selectivity is reported to be significantly improved following structural modification, and derivative 23 is first shown to be able to inhibit lung cancer growth via the PKM2/STAT3 phosphorylation signaling pathway in vitro, indicating the potential value of derivative 23 in treating lung cancer.

The Long Noncoding RNA H19 Promotes Fibrotic Processes in Lens Epithelial Cells.

Purpose: The purpose of this study was to investigate the role of lncRNA H19 in epithelial-mesenchymal transition (EMT) and its molecular mechanism in fibrotic cataracts. Methods: TGF-ß2-induced EMT was induced in human lens epithelial cell line (HLECs) and rat lens explants to mimic posterior capsular opacification (PCO) in vitro and in vivo. Anterior subcapsular cataract (ASC) was induced in C57BL/6J mice. The long noncoding RNA (lncRNA) H19 (H19) expression was detected by RT-qPCR. Whole-mount staining of lens anterior capsule was used to detect α-SMA and vimentin. Lentiviruses carrying shRNA or H19 vector were transfected in HLECs to knockdown or overexpress H19. Cell migration and proliferation were characterized by EdU, Transwell, and scratch assay. EMT level was detected by Western blotting and immunofluorescence. The rAAV2 carrying mouse H19 shRNA was injected into ASC model mouse anterior chambers as a gene therapy to determine its therapeutic potential. Results: PCO and ASC models were built successfully. We found H19 upregulation in PCO and ASC models in vivo and in vitro. Overexpression of H19 by lentivirus transfection increased cell migration, proliferation, and EMT. In addition, H19 knockdown by lentivirus suppressed cell migration, proliferation, and EMT levels in HLECs. Moreover, transfection of rAAV2 H19 shRNA alleviated fibrotic area in ASC mouse lens anterior capsules. Conclusions: Excessive H19 participates in lens fibrosis. Overexpression of H19 increases, whereas knockdown of H19 ameliorates HLECs migration, proliferation, and EMT. These results demonstrate H19 might be a potential target for fibrotic cataracts.

The Clinical and Radiological Outcomes of Subtrochanteric Osteotomy in Crowe Type IV Hip Dysplasia: A Comparison of Three Different Stem Designs.

AIMS: The purpose of this study was to determine whether there are differences in clinical and radiographic outcomes among three different stem designs for subtrochanteric osteotomy in Crowe type IV developmental dysplasia of the hip (DDH). METHODS: A retrospective analysis of prospectively collected data was undertaken from a consecutive series of 37 Crowe type IV DDHs treatment of noncemented total hip arthroplasty with chevron subtrochanteric osteotomy in 30 patients. Patients are divided into three groups, including Ribbed group (using Link Ribbed stem; n = 14), Synergy group (using Synergy stem; n = 9), and Link Classic Uncemented (LCU) group (using LCU stem; n = 14), according to the design of the stem. The clinical and radiographic outcomes were evaluated. RESULTS: All patients were followed for 36 months. The time of bone union of the LCU stem was significantly longer than that of the Synergy stem (P = 0.02) and the Ribbed stem (P > 0.05); the time of bone union of the Ribbed stem was longer than that of the Synergy stem (P > 0.05). The length of stem in the distal femur of the Ribbed stem (P = 0.000) and the Synergy stem (P = 0.001) is significantly longer than that of the LCU stem. There were three hips with malunion, stem loosening, and varus alignment, which were observed in the LCU stem. None of these were observed in Ribbed and Synergy stems. In total hip arthroplasty with a noncemented stem combined with subtrochanteric femoral osteotomy for Crowe IV DDH, 89.2% hips (33/37) can achieve good and excellent clinical outcomes. There were three hips (1 hip in the Ribbed stem and two in the LCU stem) with fair clinical outcomes and one hip (LCU stem) with poor clinical outcomes. CONCLUSIONS: Although Ribbed, Synergy, and LCU stems have similar clinical outcomes, the LCU stem has a tendency to a varus position, longer union time, malunion, and stem loosening, when compared with the Ribbed and Synergy stems. We recommend against adoption of the LCU stem for Crowe IV DDH with subtrochanteric femoral osteotomy. LEVEL OF EVIDENCE: Level III, therapeutic study.

Development of Nickel Selenide@polydopamine Nanocomposites for Magnetic Resonance Imaging Guided NIR-II Photothermal Therapy.

The penetration depth of near-infrared laser has greatly restricted the development of most photothermal agents. Recently, photothermal agents in the second near-infrared (NIR-II) window have drawn great attention as they can overcome above barrier. Herein, a novel "all in one" NIR-II responsive nanoplatform (nickel selenide @polydopamine nanocomposites, NiSe@PDA NCs) based on in situ coating the polydopamine (PDA) on the surface of biomineralized nickel selenide nanoparticles (NiSe NPs) for dual-model imaging-guided photothermal therapy is reported. Under the illumination of NIR-II laser (1064 nm), the photothermal conversion efficiency of NiSe@PDA NCs can reach 48.4%, which is higher than that of single NiSe NPs due to the enhanced molar extinction coefficient. In addition, because of the paramagnetic effect of NiSe NPs, the constructed NiSe@PDA NCs can be acted as T1 contrast agent for magnetic resonance imaging (MRI). Most importantly, the MRI contrast effect is enhanced with the coating of PDA layer due to the loose structure of PDA. Ultimately, both in vitro and in vivo experiments demonstrate that the developed NCs can achieve efficient MRI-guided photothermal therapy for treating malignant tumor. Therefore, the designed NiSe@PDA NCs with excellent features show great potential for clinical MRI-guided cancer therapy.

Synthesis and Aggregation Behavior of Jellyfish-Shaped Triazine Hexamer Quaternary Ammonium Chloride Surfactant.

A novel jellyfish-shaped triazine hexamer quaternary ammonium chloride surfactant (TH12QC) was synthesized, which consisted of one triazine spacer group and six long flexible hydrophobic chains. The molecular structure and aggregation behavior of TH12QC was investigated by nuclear magnetic resonance (NMR), surface tension, electrical conductivity, dynamic light scattering (DLS), transmission electron microscope (TEM), etc. The results show that the jellyfish-shaped TH12QC has better surface activity and lower surface tension than traditional ionic and Gemini surfactants in aqueous solution. There are two inflection points in the curve of conductivity versus concentration of the TH12QC aqueous solution, which correspond to the critical aggregation concentration (CAC) and the critical micelle concentration (CMC) respectively. The existence of CAC indicates that there is a pre-aggregation process before TH12QC forms micelles. The results of DLS and TEM show that network pre-aggregation, spherical aggregation and dense spherical aggregation were observed in different concentration of TH12QC aqueous solution, and the electrostatic equilibrium of the system subtly depends on the concentration of the solution. In addition, intramolecular and intermolecular hydrogen bonding is also an important factor. This study provides a method for studying the aggregation behavior and morphology of oligomeric surfactants with rigid spacer groups.

Factor analysis of electroacupuncture and selective serotonin reuptake inhibitors for major depressive disorder: an 8-week controlled clinical trial.

BACKGROUND: There is evidence supporting electroacupuncture (EA) for the treatment of major depressive disorder (MDD), but its characteristics have not been well investigated. OBJECTIVE: To investigate the effectiveness and characteristics of EA in MDD. METHODS: 60 subjects were enrolled-35 in the EA group and 25 in the selective serotonin reuptake inhibitor (SSRI) group based on their preferences-in an 8-week non-randomised controlled clinical trial. The 24-item Hamilton depression rating scale (HAMD-24) and clinical global impression (CGI) were adopted for clinical assessment. The Columbia suicide severity rating scale and adverse event form were used to measure safety and tolerability. The characteristics of EA and SSRIs were compared by analysing seven factors of the HAMD-24. RESULTS: There was no significant difference between the two groups in terms of HAMD-24 response rate after intervention (P>0.05). Patients treated with EA demonstrated a significant reduction in CGI scores (P<0.05) with fewer adverse events compared with SSRIs (P<0.01). Although HAMD-24 factor analysis showed both EA and SSRIs could improve factor scores in cognitive impairment, diurnal variation, retardation, sleep disturbance, anxiety/somatisation and feelings of despair, EA showed greater improvement in anxiety/somatisation and feelings of despair than SSRIs (P<0.05). CONCLUSIONS: There was no significant difference between EA and SSRIs in the treatment of MDD with respect to our primary outcome. However, as a potential therapy for MDD, EA appeared to result in greater symptom improvement than SSRI treatment with respect to anxiety/somatisation and feelings of despair. The results of this secondary analysis should be interpreted cautiously given the inherent issues of multiple testing.

An environmentally sustainable plasticizer toughened polylactide.

Cardanol (CD), derived from renewable natural cashew nutshell liquid, has been used as a new plasticizer for polylactide (PLA), to create blends which retain the environmentally friendly features of PLA. The differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA) and scanning electron microscopy (SEM) results all reveal that PLA and CD show good miscibility at low CD content. CD significantly decreased the glass transition temperature and enhanced the crystallization ability of PLA, demonstrating good plasticizing efficiency with PLA. At 10 wt% CD, ultimate elongation and impact toughness increased to 472% and 9.4 kJ m-2, respectively, which represented improvements of 31-fold and 2.6-fold over the corresponding measurements for neat PLA. The plasticization effect of CD was also demonstrated by the decreased melt complex viscosity and shear storage modulus at lower CD content for the blends when compared with neat PLA. Thus, the investigated CD presents an interesting candidate for a PLA plasticizer, meeting "double green" criteria. No cytotoxicity was found for the blends and hence they may be suitable for biomedical applications.

The Role of MAPK and Dopaminergic Synapse Signaling Pathways in Antidepressant Effect of Electroacupuncture Pretreatment in Chronic Restraint Stress Rats.

Acupuncture has demonstrated the function in ameliorating depressive-like behaviors via modulating PKA/CREB signaling pathway. To further confirm the antidepressant mechanism of EA on the mitogen-activated protein kinase (MAPK) and dopaminergic synapse signaling pathways, 4 target proteins were detected based on our previous iTRAQ analysis. Rats were randomly divided into control group, model group, and electroacupuncture (EA) group. Except for the control group, all rats were subjected to 28 days of chronic restraint stress (CRS) protocols to induce depression. In the EA group, EA pretreatment at Baihui (GV20) and Yintang (GV29) was performed daily (1 mA, 2 Hz, discontinuous wave, 20 minutes) prior to restraint. The antidepressant-like effect of EA was measured by body weight and open-field test. The protein levels of DAT, Th, Mapt, and Prkc in the hippocampus were examined by using Western blot. The results showed EA could ameliorate the depression-like behaviors and regulate the expression levels of Prkc and Mapt in CRS rats. The effect of EA on DAT and Th expression was minimal. These findings implied that EA pretreatment could alleviate depression through modulating MAPK signaling pathway. The role of EA on dopaminergic synapse signaling pathways needs to be further explored.

Simultaneous determination of trace Cd(II), Pb(II) and Cu(II) by differential pulse anodic stripping voltammetry using a reduced graphene oxide-chitosan/poly-l-lysine nanocomposite modified glassy carbon electrode.

The reduced graphene oxide (RGO) and Chitosan (CS) hybrid matrix RGO-CS were coated onto the glassy carbon electrode (GCE) surface, then, poly-l-lysine films (PLL) were prepared by electropolymerization with cyclic voltammetry (CV) method to prepare RGO-CS/PLL modified glassy carbon electrode (RGO-CS/PLL/GCE) for the simultaneous electrochemical determination of heavy metal ions Cd(II), Pb(II) and Cu(II). Combining the advantageous features of RGO and CS, RGO and CS are used together because the positively charged CS can interact with the negatively changed RGO to prevent their aggregation. Furthermore, CS has many amino groups along its macromolecular chains and possessed strongly reactive with metal ions. Moreover, PLL modified electrodes have good stability, excellent permselectivity, more active sites and strong adherence to electrode surface, which enhanced electrocatalytic activity. The RGO-CS/PLL/GCE was characterized voltammetrically using redox couples (Fe(CN)63-/4-), complemented with electrochemical impedance spectroscopy (EIS). Differential pulse anodic stripping voltammetry (DPASV) has been used for the detection of Cd(II), Pb(II) and Cu(II). The detection limit of RGO-CS/PLL/GCE toward Cd(II), Pb(II) and Cu(II) is 0.01µgL-1, 0.02µgL-1 and 0.02µgL-1, respectively. The electrochemical parameters that exert influence on deposition and stripping of metal ions, such as supporting electrolytes, pH value, deposition potential, and deposition time, were carefully studied.

Electroacupuncture and cognitive behavioural therapy for sub-syndromal depression among undergraduates: a controlled clinical trial.

BACKGROUND: Individuals with sub-syndromal depression (SSD) are at increased risk of incident depressive disorders; however, the ideal therapeutic approach to SSD remains unknown. OBJECTIVE: To evaluate the effects of electroacupuncture (EA) and cognitive behavioural therapy (CBT), alone or in combination, on depressive symptoms. METHODS: Undergraduate students with SSD were recruited and allocated to one of four groups based on their preferences: EA (n=6), CBT (n=10), EA+CBT (n=6), and untreated control (n=11) groups. Six weeks of treatment were provided in the first three groups. Clinical outcomes were measured using the 17-item Hamilton Depression (HAMD-17) rating scale, Center for Epidemiologic Depression (CES-D) scale, WHO Quality of Life-Brief version (WHOQOL-BREF) questionnaire, and clinical remission rate. RESULTS: All 33 subjects were included in an intent-to-treat analysis. Statistically significant improvements in HAMD-17, CES-D, and WHOQOL-BREF scores and a higher remission rate were found in the EA, CBT, and EA+CBT intervention groups compared with the control group (all p<0.05). No significant differences were found between the three intervention groups. HAMD-17 factor score analysis revealed that EA reduced sleep disturbance scores more than CBT or EA+CBT (p<0.05), and CBT reduced retardation scores more than EA (p<0.01). EA+CBT reduced anxiety/somatisation scores more than EA or CBT (p<0.05) and retardation scores more than EA (p<0.05). CONCLUSIONS: Early intervention may alleviate depressive symptoms in SSD. EA and CBT may have differential effects on certain symptoms. Combination therapy targeting both physical and psychological symptoms may represent an ideal strategy for SSD intervention. However, randomised trials with larger sample sizes are needed. TRIAL REGISTRATION NUMBER: ChiCTR-TRC-10000889; Results.

Electroacupuncture pretreatment exhibits anti-depressive effects by regulating hippocampal proteomics in rats with chronic restraint stress.

The clinical effect of electroacupuncture on depression is widely recognized. However, the signal transduction pathways and target proteins involved remain unclear. In the present study, rat models of chronic restraint stress were used to explore the mechanism by which electroacupuncture alleviates depression. Rats were randomly divided into control, model, and electroacupuncture groups. Chronic restraint stress was induced in the model and electroacupuncture groups by restraining rats for 28 days. In the electroacupuncture group, electroacupuncture pretreatment at Baihui (GV20) and Yintang (GV29) acupoints was performed daily (1 mA, 2 Hz, discontinuous wave, 20 minutes) prior to restraint for 28 days. Open field tests and body weight measurements were carried out to evaluate the depressive symptoms at specific time points. On day 28, the crossing number, rearing number, and body weights of the model group were significantly lower than those in the control group. Behavior test results indicated that rat models of depressive-like symptoms were successfully established by chronic restraint stress combined with solitary raising. On day 28, an isobaric tag for a relative and absolute quantitation-based quantitative proteomic approach was performed to identify differentially expressed proteins in hippocampal samples obtained from the model and electroacupuncture groups. The potential function of these differential proteins was predicted through the use of the Cluster of Orthologous Groups of proteins (COG) database. Twenty-seven differential proteins (uncharacteristic proteins expected) were selected from the model and electroacupuncture groups. In addition to unknown protein functions, COG are mainly concentrated in general prediction function, mechanism of signal transduction, amino acid transport and metabolism groups. This suggests that electroacupuncture improved depressive-like symptoms by regulating differential proteins, and most of these related proteins exist in nerve cells.

Electrochemical sensor for Isoniazid based on the glassy carbon electrode modified with reduced graphene oxide-Au nanomaterials.

A sensitive electrochemical sensor has been fabricated to detect Isoniazid (INZ) using reduced graphene oxide (RGO) and Au nanocomposites (RGO-Au). RGO-Au nanocomposites were synthesized by a solution-based approach of chemical co-reduction of Au(III) and graphene oxide (GO), and were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy, and Fourier transform infrared (FT-IR). The Au nanoparticles separate the RGO sheets in the precipitate and prevent RGO sheets from aggregation upon π-π stacking interactions. RGO-Au nanocomposites were used to modify the glassy carbon electrode (GCE). The electrochemical properties of RGO-Au/GCE were investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), and the RGO-Au/GCE exhibited remarkably strong electrocatalytic activities towards INZ. Under the optimized conditions, there was linear relationships between the peak currents and the concentrations in the range of 1.0×10(-7)M to 1.0×10(-3)M for INZ, with the limit of detection (LOD) (based on S/N=3) of 1.0×10(-8)M for INZ.

Fabrication of multifunctional SiO2@GN-serum composites for chemo-photothermal synergistic therapy.

Recently, the chemo-photothermal synergistic therapy has become a potential method for cancer treatment. Herein, we developed a multifunctional nanomaterial for chemo-photothermal therapeutics based on silica and graphene core/shell structure (SiO2@GN) because of the ability of GN to convert light energy into heat. Serum protein was further modified onto the surface of GN (SiO2@GN-Serum) to improve the solubility and stability of GN-based nanoparticles in physiological conditions. The as-synthesized SiO2@GN-Serum nanoparticles (NPs) have been revealed to have high photothermal conversion efficiency and stability, as well as high storage and release capacity for anticancer drug doxorubicin (SiO2@GN-Serum-Dox). The therapeutic efficacy of SiO2@GN-Serum-Dox has been evaluated in vitro and in vivo for cervical cancer therapy. In vitro cytotoxicity tests demonstrate that SiO2@GN-Serum NPs have excellent biocompatibility. However, SiO2@GN-Serum-Dox NPs show higher cytotoxicity than SiO2@GN-Serum and free Dox under irradiation with NIR laser at 1.0 W/cm(2) for 5 min owing to both SiO2@GN-Serum-mediated photothermal ablation and cytotoxicity of light-triggered Dox release. In mouse models, the tumor growth is significantly inhibited by chem-photothermal effect of SiO2@GN-Serum-Dox. Overall, compared with single chemotherapy or photothermal therapy, the combined treatment demonstrates better therapeutic efficacy. Our results suggest a promising GN-based core/shell nanostructure for biomedical applications.

The Alterations of IL-1Beta, IL-6, and TGF-Beta Levels in Hippocampal CA3 Region of Chronic Restraint Stress Rats after Electroacupuncture (EA) Pretreatment.

Immunological reactions induced by proinflammatory cytokines have been involved in the pathogenesis of depressive disorders. Recent studies showed that Electroacupuncture (EA) was able to reduce depressive symptoms; however, the underlying mechanism and its potential targets remain unknown. In the present study, we used a 21-day chronic restraint stress rats as a model to investigate how EA could alleviate depression. Open field test was carried out to evaluate the depressive symptoms at selected time points. At the end of study, immunohistochemistry (IHC) was performed to detect the expressions of IL-1beta, IL-6, and TGF-beta in hippocampal CA3 region. We found that chronic restraint stress significantly decreased behavioral activities, whereas EA stimulation at points Baihui (GV 20) and Yintang (GV 29) showed protective effect during the test period. In addition, the IL-1beta, IL-6, and TGF-beta increased in rats exposed to chronic restraint stress, while EA downregulated the levels of IL-1beta and IL-6. These findings implied that EA pretreatment could alleviate depression through modulating IL-1beta and IL-6 expression levels in hippocampal CA3 region.

[Protective effect of Rhodiola extract against cisplatin-induced damage to TM4 sertoli cells in mice].

OBJECTIVE: To investigate the preventive effect of Rhodiola extract on cisplatin (cDDP)-induced testicular toxicity in mouse TM4 Sertoli cell line and its possible mechanism in vitro. METHODS: We treated mouse TM4 Sertoli cells with Rhodiola extract and/or cDDP. Then we detected the proliferation of the TM4 cells by MTT assay, observed their morphological changes, and determined the contents of malondialdehyde (MDA), superoxide dismutase (T-SOD) and glutathione (GSH) in the cells. RESULTS: MTT assay showed that Rhodiola extract at the concentration of 0.0125-2.5 mg/L significantly inhibited the cDDP-induced decrease in the proliferation of the TM4 cells (P < 0.01) and improved their morphological changes. Anti-oxidation test exhibited a dramatically increased level of MDA in the TM4 cells treated with cDDP at 0.0147 g/L as compared with the normal control cells ([3.63 +/- 0.02] vs [2.15 +/- 0.02] nmol/mg prot, P < 0.01) and decreased levels of T-SOD ([6.57 +/- 0.05] vs [10.86 +/- 0.02] U/mg prot, P < 0.01) and GSH ([1.42 +/- 0.06] vs [2.59 +/- 0.05] mg/g prot, P < 0.01). Rhodiola extract at 0.1 mg/L significantly reduced the MDA content ([1.94 +/- 0.00] nmol/mg prot, P < 0.01) and the activity of T-SOD ([8.50 +/- 0.02] U/mg prot, P < 0.01) and GSH ([2.41 +/- 0.04] mg/g prot, P < 0.01) in the TM4 cells treated with cDDP. CONCLUSION: Rhodiola extract can significantly inhibit cDDP-induced damage to TM4 cells in mice, which may be associated with its antioxidant activity.

The effects of vitamin C on DDP-induced anemia in rats.

The aim of this study was to investigate the effects of vitamin C on cisplatin (DDP)-induced anemia and explore its possible mechanisms in rats. Adult male Sprague-Dawley rats were randomly divided into six groups: control, vitamin C 50, vitamin C 100, DDP, DDP plus vitamin C 50 and DDP plus vitamin C 100-treated groups. DDP was intravenous injected as a single dose and vitamin C was administered by gavage. Serum erythropoietin (Epo), hemoglobin (Hb) and blood urea nitrogen (BUN) concentration were measured 4 and 14 days after DDP treatment. The changes of renal tissue were examined by light microscope. Administration of DDP to rats induced anemia and nephrotoxicity, characterized with a significant decrease in serum Epo and Hb and increase in BUN concentrations. Pathological examination revealed that DDP caused significant renal damage in rats. Vitamin C administration produced amelioration in biochemical indices of anemia and nephrotoxicity and in histological change when compared to group DDP alone; concurrent administration of vitamin C at doses of 100 mg/kg being more effective. Results from this study indicate that the novel natural antioxidant vitamin C might have protective effect against DDP-induced anemia in rats.

Effects of particle morphology, pore size and surface coating of mesoporous silica on Naproxen dissolution rate enhancement.

Naproxen (Nap) is a commonly used drug for antiphlogosis and analgesia, but its dissolution rate in water is quite low. In this work, the dissolution behavior of Nap after loading in mesoporous silica materials was investigated in a simulated intestinal fluid (pH=6.8). The results indicated that the pore sizes, morphologies and surface chemical groups of the mesoporous silica were significant factors on the dissolution behavior of Nap. The physical state of encapsulated Nap was affected by the pore sizes of mesoporous silica, which influenced its dissolution rate. Amorphous Nap exhibited a higher dissolution rate than crystallized Nap, even though the larger pore size could facilitate its diffusion from the matrix. The effect of the morphology of mesoporous silicas on the dissolution of Nap can be ascribed to the length of pore channels, that the longer channel showed a longer diffusion pathway of Nap. Moreover, the release rate of Nap from functionalized mesoporous materials was effectively controlled compared with that of unmodified materials.