OBJECTIVETo evaluate the effect of melittin and 5-Fu, DDP, and TXT on human gastric cancer cell line BGC-823 and to primarily explore their possible mechanisms.

METHODSMedian effect analysis was employed to determine the interaction between melittin and 5-Fu, DDP, TXT by analyzing the relationship between fraction affected (FA) and the combination index (CI) acquired from the dose-effect curve. Expressions of chemotherapeutic agent-associated genes of BGC-823 cells with or without treatment were measured by real-time fluorescent quantitative PCR.

RESULTS(1) Both melittin and chemotherapeutic agents inhibited the growth of BGC-823. (2) For BGC-823 cells were acted by 5-Fu +melittin, when FA ranged between 0.35-0.75, CI was less than 1. For BGC-823 cells were acted by DDP + melittin, when FA ranged 0.55 or so, CI = 1; when Fa ranged below 0.55, CI was less than 1. For BGC-823 cells were acted by TXT + melittin, CI less than 1 could be seen in the whole interval. (3) After treatment suppressed were the expressions of chemotherapeutic agent-associated genes of BGC-823 cells such as thymidylate synthetase (TS), excision repair cross-complementing gene 1 (ERCC1), breast cancer susceptibility gene 1 (BRCA1), beta-tubulin III (TUBB3), and microtubule-associated protein tau (MAPT).

CONCLUSIONSMelittin had a synergistic effect on the cytotoxicity of chemotherapeutic agents. The possible mechanisms might be associated with down-regulating chemotherapeutic agent-associated genes.

Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Synergism ; Fluorouracil ; pharmacology ; Humans ; Melitten ; pharmacology

It has been well established that the recovery ability of central nervous system (CNS) is very poor in adult mammals. As a result, CNS trauma generally leads to severe and persistent functional deficits. Thus, the investigation in this field becomes a "hot spot". Up to date, accumulating evidence supports the hypothesis that the failure of CNS neurons to regenerate is not due to their intrinsic inability to grow new axons, but due to their growth state and due to lack of a permissive growth environment. Therefore, any successful approaches to facilitate the regeneration of injured CNS axons will likely include multiple steps: keeping neurons alive in a certain growth-state, preventing the formation of a glial scar, overcoming inhibitory molecules present in the myelin debris, and giving direction to the growing axons. This brief review focused on the recent progress in the neuron regeneration of CNS in adult mammals.
Animals ; Axons ; physiology ; Central Nervous System Diseases ; complications ; metabolism ; pathology ; Humans ; Mammals ; physiology ; Nerve Regeneration ; physiology

This study is to screen the Chinese herbal compounds which could inhibit the production of Abeta and investigate the underlying mechanism. Ten types of compounds which have potential value in the treatment of AD were selected as initial screening trial. The cell models which used could overexpress Abeta and beta-secretases or Abeta and gamma-secretases. Extracellular Abeta was determined by ELISA after the cell models treated with different concentrations of compounds (0.5-100 micromol x L(-1)), separately. Then the compounds were selected which could inhibit extracellular Abeta and their best concentration ranges were decided, too. Furthermore, the cell viability and apoptosis rate, the level of intracellular Abeta, beta and gamma-secretases were determined after the cell models treated with different concentrations of selected compounds. The results showed that 4 of the 10 compounds could reduce the level of extracellular Abeta; they were cryptotanshinone, astragalosides, gastrodin and paeoniflorin, and their best concentration ranges were 0.5-5.0, 0.5-5.0, 5.0-50, 1.0-25 micromol x L(-1), respectively. Further study indicated that the 4 selected compounds were nontoxic to the cellular models and lowering intracellular Abeta were more effective compared with extracellular; of which astragalosides and gastrodin showed dose-dependent inhibition to the activities of beta and gamma-secretases, with the maximum inhibiting rates of 78.2% and 80.3%, respectively. In conclusion, cryptotanshinone, astragalosides, gastrodin and paeoniflorin could inhibit the expression and secretion of Abeta, and the underlying inhibiting mechanism of astragalosides and gastrodin were related with the reduction of the beta and gamma-secretase activities, respectively.
Amyloid Precursor Protein Secretases ; metabolism ; Amyloid beta-Peptides ; antagonists & inhibitors ; Apoptosis ; Benzyl Alcohols ; pharmacology ; Cell Line ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; pharmacology ; Glucosides ; pharmacology ; Humans ; Monoterpenes ; pharmacology ; Phenanthrenes ; pharmacology ; Saponins ; pharmacology

Objective To research and prepare the individualized knee in vitro guided plate by 3D printing technique and to investigate the feasibility of its application in 8-plate epiphysiodesis.Methods Twelve children patients with knee varus or valgum in our hospital from January 2014 and November 2016,7 boys and 5 girls,average age of 8.2 years old,were performed the lower extremity continuous spiral CT scanning in the knee straight position.The Dicom format stored CT data were imported into software Mimics 15.0 for reconstructing the knee joint 3D model.The knee joint data after reconstruction were guided into software Geomagic1 1.0 with the.stl format.According to the demand that screws without perforating epiphyseal and joint surface,paralle ling to the epiphyseal and locating in the anterior-posterior median line of epiphyseal,the 8-plate placing screw navigation template was designed and printed by using the 3D printing technique;the 8-plate plate and screw internal fixation was conducted by intraoperative template location.The placed screw position was evaluated by postoperative CT.Results The imaging identification showed that 8-plate epiphysiodesis by using 3D printing individualized in vitro guided plate had accurate screw placement.The cases were followed from 6 months to 2 years,the satisfactory orthopedic effect was obtained in all cases.Conclusion Preparing the individualized knee in vitro guided plate by applying 3D printing technique in assisted 8-plate epiphysiodesis for treating child knee varus or valgum has accurate screw position and satisfactory effect.

Dexmedetomidine , a strong potent and highly selective α2 -adrenoceptor agonist , has an analgesic and dose -dependent sedative property with minimal effects on respiratory depression.It is the only tranquilizing drug which can be arousal currently and is also widely used in clinical applications because of its special pharmacologic characteris-tics.However, dexmedetomidine has large individual differences which made the control of administration dosage more difficult , especially in special populations.So this review article summarized the latest litera-tures about pharmacokinetics of dexmedetomidine in children , the elder-ly , hepatic and renal insufficiency patients and other special populations.

Aim To determine the effect of exosomes from lipopolysaccharide-treated human bone marrow mesenchymal stem cells on proportion of Ly6Chigh and Ly6Clow monocytes/macrophages in inflammatory micro- environment. Methods BMSCs were obtained by gra-dient centrifugation, identified and then treated with li-popolysaccharide for 48 h. The exosomes were purified from conditional medium with or without LPS treatment and identified by CD63 protein using Western blot and transmission electron microscope. The diameters and concentration were detected by Nanoparticle Trafficking Analysis ( NTA ) . The monocytes/macrophages were sorted from bone marrow of the mice by magnetic beads. Cells were co-cultured with exosomes for 24 hours, and then treated with LPS for 48 hours. The proportion of Ly6C monocytes/macrophages was detec-ted by flow cytometry. Inflammatory cytokines in cell supernatant were investigated using ELISA. Results BMSCs surface markers CD44, CD90 were positively detected, but CD34, CD45 were not expressed. BM-SCs presented adipogenic differentiation ability. Exo-somes were positively expressing CD63 protein, and NTA showed that the diameters of exosomes were up to (82.4 ± 3.7 ) nm. BMSCs stimulated by LPS pro- duced more exosomes ( P < 0.01 ) . Exosomes from BMSCs with or without LPS treatment could increase the ratio of Ly6Chigh monocytes (P<0.01) and down-regulate the ratio of Ly6Chigh macrophages (P<0.05), and the effect of LPS treated-exosomes was more signif-icant than untreated-exosomes (P<0.05). Moreover, the concentration of IL-6 was also elevated under exo-somes treatment ( P <0.05 ) . Conclusions Human bone marrow mesenchymal stem cells-derived exosomes contribute to the regulation of Ly6Chigh monocytes/mac-rophages, indicating that they could be involved in the therapeutic treatment of inflammatory diseases.

AIMTo investigate the chronic effect of palmitic acid (PA) on apoptosis of pancreatic islet beta-cells and the possible mechanism.

METHODSInsulinoma cell line (MIN6 cells) were used in this study. After being incubated in PA (0.1 - 1.6 mml/L) for 24 and 48 hours, MTT method was used to evaluate the livability. After being incubated for 48 h, Hoechst-PI and Annexin-V-FTTC/PI FACS were used to estimate the apoptosis in each group, Western-blotting assay was used to estimate the protein level of p-Akt, Akt, Bax and Bcl-2.

RESULTSChronic PA dose-dependently (1) decreased the availability and increased the apoptosis of MIN6 cells; (2) decreased the phosphorylation of Akt and Bcl-2, but had no significant effects on Akt and Bax.

CONCLUSIONChronic PA dose-dependently induced apoptosis of MIN6 cells, and this effect was possibly regulated by Akt/Bcl-2.

Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cells, Cultured ; Insulinoma ; pathology ; Islets of Langerhans ; pathology ; Mice ; Oxidative Stress ; physiology ; Palmitic Acid ; pharmacology ; Proto-Oncogene Proteins ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; Signal Transduction ; drug effects ; physiology ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo investigate changes of autophagy after traumatic brain injury (TBI) and its possible role.

METHODSRat TBI model was established by controlled cortical injury system. Autophagic double membrane structure was detected by transmission electronic microscope. Microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1 were also used to investigate the activation of autophagy post-TBI. Double labeling with LC3 and caspase-3, or Beclin 1 and Fluoro-Jade to show the relationship between autophagy and apoptosis or neuron degeneration after TBI.

RESULTSAn increase of autophagic double membrane structure was observed in early stage (1 h), and the increase lasted for at least 32 d post-TBI. LC3 and Beclin 1 proteins also began to elevate at 1 h time point post-TBI in neurons, 3 d later in astrocytes, and peaked at about 8 d post-TBI. In both cell types, LC3 and Beclin 1 maintained at a high level until 32 d post-TBI. Most LC3 and Beclin 1 positive cells were near the side (including hippocampus), but not in the core of the injury. In addition, in the periphery of the injury site, not all caspase-3 positive (+) cells merged with LC3 (+) cells post-TBI; In hippocampal area, almost all Beclin 1 (+) neurons did not merge with Fluoro-Jade (+) neurons from 1 h to 48 h post-TBI.

CONCLUSIONAutophagy is activated and might protect neurons from degeneration at early stage post-TBI and play a continuous role afterwards in eliminating aberrant cell components.

Animals ; Apoptosis Regulatory Proteins ; metabolism ; Astrocytes ; metabolism ; pathology ; Autophagy ; Beclin-1 ; Brain ; metabolism ; pathology ; Brain Injuries ; metabolism ; pathology ; physiopathology ; Caspase 3 ; metabolism ; Cell Membrane ; metabolism ; pathology ; Cytoprotection ; Disease Models, Animal ; Fluoresceins ; Fluorescent Antibody Technique ; Hippocampus ; metabolism ; pathology ; physiopathology ; Male ; Microscopy, Electron, Transmission ; Microtubule-Associated Proteins ; metabolism ; Nerve Degeneration ; metabolism ; pathology ; physiopathology ; Neurons ; metabolism ; pathology ; Organic Chemicals ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Up-Regulation

OBJECTIVE To investigate the effect of LW- AFC, a new formula of the main active components extracted from Liuwei Dihuang decoction, on treatment of Alzheimer disease (AD) in mouse models. METHODS After treatment LW- AFC, mice were cognitively evaluated in behavioral experiments. Neuron loss, amyloid-β(Αβ) deposition, and Αβ level were analyzed using Nissl staining, immunofluorescence, and an AlphaLISA assay, respectively. Multiplex bead analysis, a radioimmunoassay, immunochemiluminometry, and an ELISA were used to measure cytokine and hormone levels. Lymphocyte subsets were detected using flow cytometry. RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1 mice, including the impairment of object recognition memory, spatial learning and memory, and active and passive avoidance. In addition, LW-AFC alleviated the neuron loss in the hippocampus, suppressed Αβ deposition in the brain, and reduced the concentration of Aβ1- 42 in the hippocampus and plasma of APP/PS1 mice. LW-AFC treatment also significantly decreased the secretion of corticotropin-releasing hormone and gonadotropin-releasing hormone in the hypothalamus, and adrenocorticotropic hormone, luteinizing hormone, and follicle- stimulating hormone in the pituitary. Moreover, LW-AFC increased CD8+CD28+T cells, and reduced CD4+CD25+Foxp3+T cells in the spleen lymphocytes, down- regulated interleukin(IL)- 1β, IL- 2, IL- 6, IL- 23, granulocyte- macrophage colony stimulating factor, and tumor necrosis factor-α and -β, and up-regulated IL-4 and granulocyte colony stimulating factor in the plasma of APP/PS1 mice. CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic micevia the restoration of the NIM network to a greater extent than either memantineor donepezil, which supports the use of LW-AFC as a potential agent for AD therapy.

OBJECTIVE: To investigate the status of vaccination in children with human immunodeficiency virus (HIV) infection. METHODS: A questionnaire survey was performed in 148 children in Hunan province, China who were registered in China's Acquired Immune Deficiency Syndrome Comprehensive Response Information Management System up to December 31, 2016 and were aged <15 years at the time of confirmed diagnosis of HIV infection. The information on vaccination, diagnosis of HIV infection, and diagnosis and treatment of related diseases was collected. RESULTS: Of the 148 children with HIV infection, there were 70 boys (47.3%) and 78 girls (52.7%); 140 children had an age of 3.8 (0.2-14.8) years at the time of confirmed diagnosis, and 8 children refused to answer this question. Mother-to-child transmission was found in 133 children (91.7%), blood transmission in 1 child (0.7%), and unknown in 14 children (9.5%). Of the 148 children, 129 (87.2%) received antiviral therapy and 19 (12.8%) did not receive such treatment. The vaccination rates of hepatitis B vaccine, bacille Calmette-Guérin vaccine, poliomyelitis live attenuated vaccine and diphtheria-pertussis-tetanus vaccine ranged from 70.9% to 77.7%, which was significantly lower than the national level (≥97%); the vaccination rates of the other vaccines in the National Immunization Program gradually decreased with age. No severe adverse effects were reported after vaccination. CONCLUSIONS Mother-to-child transmission is the main route of HIV infection in Chinese children. The diagnosis of children with HIV infection is significantly delayed, with low vaccination rates. Efforts should be made to strengthen early diagnosis, early treatment and vaccination in children with HIV infection, in order to improve their quality of life.
Adolescent ; Child ; Child, Preschool ; China ; Diphtheria-Tetanus-Pertussis Vaccine ; Female ; HIV ; HIV Infections ; Humans ; Infant ; Male ; Quality of Life ; Vaccination