OBJECTIVE: To establish a drug delivery system based on hyaluronic acid functionalized mesoporous silica nanoparticles MCM-41 loaded with paclitaxel (HA-MCM-41-PTX). The physical and chemical properties, in vitro drug release and the antitumor effect were investigated. METHODS: The morphological structure and particle size of MCM-41 were observed by TEM. The drug delivery system was characterized by PXRD and FTIR. The in vitro release experiments was carried out to investigate the dissolution rate of HA-MCM-41-PTX. The in vitro cells experiment was carried out to explore the mechanism of HA-MCM-41-PTX on cells. RESULTS: The drug loading capacity of HA-MCM-41-PTX was 28.75%. The in vitro drug release experiments showed that HA-MCM-41-PTX exhibited controlled release with a cumulative release of (86.19±5.11)% until 48 h. In vitro cell experiments showed that HA-MCM-41-PTX had excellent targeting effect due to the modification of hyaluronic acid, which was easier to be uptaken by cells and exhibited great antitumor effect. CONCLUSION: HA-MCM-41-PTX is an excellent drug delivery system with both controlled release and targeting antitumor effect.

Deconstruction of lignocellulosic plant cell walls to fermentable sugars by biochemical means is impeded by several poorly understood ultrastructural and chemical barriers. Pretreatment is an essential step by altering the morphological and compositional characteristics of biomass to enhance the sugar release during enzymatic hydrolysis. Therefore, getting insight into this field is necessary to improve the conversion of biomass into biofuels. In this review, we highlight our recent understanding on the impact of various promising pretreatments on biomass, with emphasis on the topochemical and ultrastructural changes of plant cell walls that are related to the reduction of recalcitrance and the consequence of saccharification. It will lend support to the scientific research and development with respect to biomass conversion.
Biofuels ; Biomass ; Carbohydrates ; chemistry ; Cell Wall ; ultrastructure ; Fermentation ; Hydrolysis ; Lignin ; chemistry ; Plant Cells ; ultrastructure

Carcinoid Tumor ; pathology ; Groin ; Humans ; Laryngeal Neoplasms ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged

Objective:To analyze gene mutations in 3 families with self-improving collodion ichthyosis.Methods:Clinical data were collected from 3 patients with self-improving collodion ichthyosis. DNA was extracted from the peripheral blood of patients and their parents, and high-throughput sequencing was performed in the patients by using a multi-gene panel targeting congenital ichthyosis. After identification of causative gene loci, Sanger sequencing was performed to bidirectionally verify the mutations in the patients and their parents.Results:All the 3 patients presented with a collodion-like membrane at birth, which was shed within 2-4 weeks after birth, and then they gradually showed similar features of mild ichthyosis, including dry skin, tiny scales at local sites, flexural involvement, mild sweating, heat intolerance, cheek flushing, mild palmoplantar keratosis or palmar hyperlinearity. Compound heterozygous mutations were identified in the ALOX12B gene of the 3 patients, including a paternal mutation c.406_408delGAG and a maternal mutation c.77T>C in case 1, a paternal mutation c.1013C>T and a maternal mutation c.1286C>G in case 2, a paternal mutation c.1232T>C and a maternal mutation c.1440C>A in case 3. Function prediction analysis showed that 4 missense mutations c.77T>C, c.1286C>G, c.1013C>T, c.1232T>C and 1 deletion mutation c.406_408delGAG may exert pathogenic effect, and 1 nonsense mutation c.1440C>A led to the generation of a termination codon encoding a truncated protein p.Tyr480Ter, which may affect the protein function and cause disease. None of the 6 mutation sites had been reported in the past.Conclusion:Compound heterozygous pathogenic mutations were identified in the ALOX12B gene of the 3 patients with self-improving collodion ichthyosis, which were inherited from their parents.

Adult ; Dust ; analysis ; Female ; Humans ; Male ; Middle Aged ; Neural Networks (Computer) ; Occupational Exposure ; Silicosis ; diagnosis ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods

Objective: A high-content analysis (HCA) method was established for the in vitro evaluation of traditional Chinese medicine and the potential hepatotoxicity components and mechanism of Polygonum multijiorum were discussed. Methods: HepG2 cells were incubated with different concentration and different incubation time of P. multijiorum extracts and components and then cells were stained with three fluorescent probes, then HCA was applied to detect the cell number, nucleus area, mitochondrial mass, and mitochondrial membrane potential. Results: The ethyl acetate extract and dichloromethane extract had served hepatotoxicity. No significant changes were observed at low concentration (0.01 and 1 μmol/L) of P. multijiorum components; However, the cell number of aloe emodin, emodin, rhein, and gallic acid decreased significantly at the concentration of 0.1 μmol/L. Aloe emodin also caused the nuclear swollen. The TC50 values of emodin and rhein obtained from the dose-response curves were similar to the previous reports. Conclusion: The aloe emodin, emodin, rhein, and gallic acid have potential hepatotoxicity that P. multijiorum induces liver injury. The hepatotoxicity of P. multijiorum may be related to mitochondria-mediated apoptosis according to the influence of P.multijiorum components on mitichondrial mass and mitochondrial membrane potential from the results. The HCA is applicable to evaluate the hepatotoxicity of traditional Chinese medicine.

Objective To study the moderate hypothermia with iced saline given intravenously with ice cap and ice sheet used in patients with severe stroke or craniocerebral trauma in order to clarify its clinical therapeutic effect and recovery of neurologic function for providing reliable clinical data.Methods A total of 84 patients suffered severe stroke (cerebral hemorrhage or cerebral infarction) or traumatic brain injury with GCS (Glascow Coma Scale) ＜8 admitted within 24 hours after onset were enrolled for study.The exclusion criteria were functional decompemsation of heart,liver,kidney and lung as cardiovascular complications of hypertension,hematological and other diseases,and craniocerebral trauma with multiple injuries of thorax,abdomen and extremities.Patients were divided into observation group and control group (n =42 in each group).The patients of two groups were managed to maintain respiratory tract patent,prevention of infection,dehydration,reduction of intracranial pressure and treated with Cytidine Diphosphate Choline,piracetam,ganglioside sodium and other conventional therapy.In control group,patients treated with ice cap and ice sheet,whereas in observation group,patients were treated with iced saline injected intravenously in addition to ice cap and sheet.At admission,the GCS score of patients was assessed and 6 months later,GCS score and Glascow Outcome Scale,(GOS) score of patients were determined,and 12 months after the treatment,quality of life score were evaluated by KPS.Results The time from onset of stroke or from trauma accident occurred to initiation of hypothermia treatment and time from initiation of hypothermia therapy to the target temperature reached in observation group were (8 ±4) hours and (3± 1 )hours respectively,and in control group,they were ( 16± 5) hours and (6 ± 2) hours,and there were significant differences between two groups ( P ＜ 0.05 ).The mean GCS score of patients at 6 months in the observation group and in the control group were (7.01 ± 1.12) and (4.02 ± 1.11 ) respectively (P ＜0.05 ) ; whereas the GOS score at 6 mouths of patients was categorized into good outcome,disabled outcome and poor outcome,and the good outcome in the observation group was significantly better than that in the control group (P ＜ 0.05 ),and no statistically significant difference in disabled outcome was found between two groups (P ＞ 0.05),and the poor outcome of GOS score was significantly lower in observation group than that in control group ( P ＜0.05 ).Twelve months after the treatment,the long-term quality of patients'life assessed by KPS score in observation group was significantly better than that in control group ( P ＜ 0.05).Conclusions The moderate hypothermia therapy by using iced saline administered intravenously combined with ice cap and ice sheet for severe stroke and head trauma patients conferred better therapeutic effects than the treatment with ice cap and ice sheet.

Objective To evaluate the ability of 3-AB to sensitize the human esophageal carcinoma cell strain (CaEs-17) to radiation in v/tro and its mechanisms. Methods CaEs-17 cells were treated with 3-AB at 0, 2.5, 7.5 mmol/L and given irradiation O, 3, 6, 9, 12 Gy. 3-AB concentration in each group was made dose-survival curve using multi-target single-hit maiths model by clonogenie assay. MTT assay was performed to observe the survival of irradiated cells.comet assay and metaphase chromosome analysis were used to measure the DNA damage degree and chromosome aberration of CaEs-17 cell after 3-AB treatment and irradiation. Results Cell survival experiments showed SER of 1.21, 1.52 for 2.5 mmol/L, 7.5 mmol/L 3-AB respectively using multi-target single-hit maths model. The survival fraction of irradiated CaEs-17 cell was decreased after 3-AB treatment. DNA damage and the chromatid breakage number of irradiated CaEs-17 cells were increased after 3-AB treatment. Conclusions 3-AB, a PARP inhibitor, can enhance the radiosensitivity of human esophageal carcinoma cell strain (CaEs-17). DNA damage repair inhibition by 3-AB might be one of the mechanisms.

Objective:To study the biological effects of new monomer 3 from Radix Curcumae on proliferation of human gastric cancer cells SGC-7901.Methods:Uing fluorescence microscope to observe the impact on SGC-7901 cells with different concentrations of the new monomer 3 at different times,using MTT assay to observe the growth inhibition rate of SGC-7901 cells,using flow cytometry to observe the apoptosis rate and cell cycle distribution of SGC-7901 cell.Results:Pronounced apoptosis had been found by fluorescence microscopy,apoptosis had a certain amount of time-dependent and concentration-dependent;Early apoptotic cells near normal morphology,normal nuclear morphology;late apoptotic cells'size shrink or round in shape,nuclear pyknosis or fragmentation.MTT method showed that the new monomer 3 had significantly inhibition on SGC-7901 cells,the half inhibition rate(IC50) was 30.14?g/mL.Flow cytometry(FCM) showed that:the new monomer 3 can increase the SGC-7901 cells in the S phase and G0/G1 and reduce it in G2/M.The change had time and concentration dependence;The apoptotic rates of dosing unit(24h,48h) compared with the control group had significant differences.The maximum apoptosis rate was 60.07%.Conclusion:The new monomer 3 inhibited human gastric cancer SGC-7901 cells significantly and had the impact on cell cycle distribution of the SGC-7901 cells and induction of apoptosis.

In this paper, the effects of the blend of nanoparticles and microneedle matrix materials on the mechanical properties of dissolving microneedles were studied mainly, so as to construct microneedles with excellent mechanical properties. Different kinds of nanoparticles (calcium carbonate, hydroxyapatite, silica), particle sizes (20, 60, 100 nm) and the proportion of prescription (2%, 6%, 10%) were blended with the matrix material [polyvinyl pyrrolidone (PVP), poly(1-vinylpyrrolidone-co-vinyl acetate)(PVP/VA)] to form dissolving microneedles. The effects of nanoparticles on the elastic modulus and hardness of the microneedles were investigated using a nanoindenter. The results showed that the elastic modulus and hardness of PVP microneedles were significantly improved by nano-calcium carbonate (P < 0.001), and the elastic modulus and hardness of PVP/VA microneedles were significantly improved by nano-hydroxyapatite (P < 0.001). When the particle size of hydroxyapatite was 20 nm, the elastic modulus of PVP/VA microneedles was (10.6 ± 1.0) GPa, and the hardness was (0.47 ± 0.06) GPa. As the size of the nanoparticles increases, the mechanical performance of the microneedles decreases. When the mass proportion of nano-hydroxyapatite increased from 2% to 6%, the elastic modulus and hardness of the microneedles were significantly improved (P < 0.001), but the effect of continue increasing the proportion of nanoparticles on the microneedles was not significant. The nano-enhanced PVP/VA dissolving microneedles has no irritant effect on intact skin and has a slight irritation to damaged skin, but they disappear completely after 72 h. Animal experiments have been approved by the Laboratory Animal Welfare and Ethics Committee of Zhejiang University of Technology. Therefore, the nano-enhanced dissolving microneedles has good biological safety. To sum up, it is necessary to select the appropriate kind of nanoparticle, particle size, and prescription ratio when microneedles constructing with a given matrix material, so as to effectively improve its mechanical performance.