Effects of nano titanium dioxide on gut microbiota based on human digestive tract microecology simulation system in vitro / 北京大学学报(医学版)

OBJECTIVE@#To explore the effects of oral exposure to titanium dioxide nanoparticles (TiO2 NPs) on the composition and structure of human gut microbiota.@*METHODS@#The particle size, shape, crystal shape and degree of agglomeration in ultrapure water of TiO2 NPs were characterized. The in vitro human digestive tract microecological simulation system was established by simulating the fluid environment and physical conditions of stomach, small intestine and colon, and the stability of the simulation system was evaluated. The bacterial communities were extracted from human feces and cultured stably in the simulated system. They were exposed to 0, 20, 100 and 500 mg/L TiO2 NPs, respectively, and the bacterial fluids were collected after 24 h of exposure. The effect of TiO2 NPs on the composition and structure of human gut microbiota was analyzed by 16S rRNA sequencing technology. Linear discriminant analysis effect size (LEfSe) was used to screen differential bacteria, and the Kyoto encyclopedia of genes and genomes (KEGG) database for functional prediction.@*RESULTS@#The spherical and anatase TiO2 NPs were (25.12±5.64) nm in particle size, while in ultra-pure water hydrated particle size was (609.43±60.35) nm and Zeta potential was (-8.33±0.22) mV. The in vitro digestive tract microecology simulation system reached a relatively stable state after 24 hours, and the counts of Enterococci, Enterobacte-rium, and Lactobacillus reached (1.6±0.85)×107, (5.6±0.82)×107 and (2.7±1.32)×107, respectively. 16S rRNA sequencing results showed that compared with the control group, the number and evenness of gut microbiota were not significantly affected at phylum, class, order, family and genus levels in TiO2 NPs groups (20, 100 and 500 mg/L). The relative abundance of some species was significantly changed, and a total of 42 different bacteria were screened between the TiO2 NPs groups (20, 100 and 500 mg/L) and the control group [linear discriminant analysis(LDA) score>3], represented by Enterobacter, Bacteroidaceae, Lactobacillaceae, Bifidobacteriaceae and Clostridium. Further predictive analysis of gut microbiota function showed that TiO2 NPs might affect oxidative phosphorylation, energy meta-bolism, phosphonate and phosphonate metabolism, and methane metabolism (P < 0.05).@*CONCLUSION@#In human digestive tract microecological simulation system, TiO2 NPs could significantly change the composition and structure of human gut microbiota, represented by Enterobacter and probiotics, and may further affect a variety of metabolism and function of the body.

Key factors in the research and development of new drugs for nonalcoholic steatohepatitis / 临床肝胆病杂志

Nonalcoholic fatty liver disease (NAFLD) has become the most important chronic liver disease in China and a major cause of liver transplantation in developed countries in Europe and America. Among the various phenotypes of NAFLD, nonalcoholic steatohepatitis (NASH) is highly likely to progress to end-stage liver disease including liver cirrhosis and liver cancer, resulting in an increase in liver-related mortality. However, there are still no therapeutic drugs for NASH at present, and many new drugs are under development in ongoing clinical trials. The research and development of new drugs for NASH require the selection of an appropriate target population and treatment outcomes depending on anti-metabolic, anti-inflammatory or anti-fibrotic effect. This article summarizes and reviews several key factors in the research and development of new drugs for NASH.

Musculoskeletal computational analysis on muscle mechanical characteristics of drivers lumbar vertebras and legs in different sitting postures

SUMMARY Using computer-aided engineering (CAE) in the concept design stage of automobiles has become a hotspot in human factor engineering research. Based on human musculoskeletal biomechanical computational software, a seated human-body musculoskeletal model was built to describe the natural sitting posture of a driver. The interaction between the driver and car in various combinations of seat-pan/back-rest inclination angles was analyzed using an inverse-dynamics approach. In order to find out the "most comfortable" driving posture of the seat-pan/back-rest, the effect of seat-pan/back-rest inclination angles on the muscle activity degree, and the intradiscal L4-L5 compression force were investigated. The results showed that a much larger back-rest inclination angle, approximately 15°, and a slight backward seat-pan, about 7°, may relieve muscle fatigue and provide more comfort while driving. Subsequently, according to the findings above, a preliminary driving-comfort function was constructed.

RESUMO O uso de engenharia assistida por computador (CAE) na fase de projeto do conceito do automóvel tornou-se um ponto de acesso na pesquisa de fatores humanos. Com base no software computacional biomecânico musculoesquelético humano, foi construído um modelo musculoesquelético sentado para descrever a postura sentada natural de um condutor. A interação entre um motorista e um carro em várias combinações de ângulos de inclinação do assento-pan/encosto foi analisada usando uma abordagem dinâmica do verso. A fim de descobrir a postura de condução "mais confortável" do assento-pan/encosto, o efeito dos ângulos de inclinação do assento-pan/dorso sobre o grau de atividade muscular e a força de compressão intradiscal L4-L5 foi investigado. Os resultados mostraram que um ângulo de inclinação para trás muito maior, aproximadamente 15°, e um ligeiro assento-pan para trás, cerca de 7°, pode aliviar a fadiga muscular e levar a dirigir em uma posição confortável. Posteriormente, de acordo com as conclusões acima expostas, foi construída uma função preliminar de conforto ao dirigir.

Superoxide dismutase 2 mediates the protective effect of berberine on neuronal damage induced by oxygen-glucose deprivation in HT22 mouse hippocampal neuronal cell / 国际脑血管病杂志

Objective To investigate the protective effect of berberine (BBR) on neuronal damage induced by oxygen-glucose deprivation (ODD) in HT22 mouse hippocampal neuronal cell,and the role of superoxide dismutase 2 (SOD2) in it.Methods HT22 cells were exposed to OGD for 4 h and then reoxygenated for 24 h to simulate ischemia-reperfusion injury.The HT22 cells were divided into control group,OGD group,BBR + OGD group,SOD2-siRNA + BBR + OGD group,and scrambled (SC)-siRNA + BBR + OGD group.Cell viability was measured by thiazole blue method.Cell morphology was observed by phase contrast microscopy.Medium lactate dehydrogenase (LDH) level,intracellular glutathione (GSH),and catalase (CAT) content were detected by colorimetric assay.The cell apoptosis rate was detected by flow cytometry.The expression level of cleaved caspase-3 was detected by Western blot analysis.Results Compared with the control group,OGD significantly decreased cell viability,intracellular GSH,and CAT level (all P ＜0.05),increased cell LDH release,apoptosis rate,and cleaved caspase-3 protein expression level (all P＜0.05).At the same time,cell morphology destruction was observed.BBR significantly reduced the above damage of HT22 cells induced by OGD (all P ＜0.05),while SOD2-siRNA significantly reversed the protective effect of BBR on HT22 cells (all P ＜0.05).Conclusions BBR significantly alleviated neuronal damage induced by recovery of oxygen-glucose after OGD.SOD2 might mediate its protective effect.

Inhibition effects of sulforaphane-induced autophagy flux to cell proliferation on ex vivo human capsular bags / 中华实验眼科杂志

Background Sulforaphane (SFN) is an effective chemopreventive agent and can regulate the biological molecular mechanisms to inhibit the overgrowth of cells.Autophagy is a biological process of maintaining cellular internal environment.Understanding the affection of SFN to biological behavior of human lens epithelial cells (LECs) and the association of SFN with autophagy is helpful for the prevention and target treatment of posterior capsule opacification (PCO).Objective This study was to investigate the eradication effeccts of SFN on residual lens cell population in vitro posterior capsule opacification (PCO) model and evaluate the mechanism of SFN-induced cell death.Methods In vitro human capsular bag models were generated from fresh donor eyes by phacoemulsification and were cultured in EMEM containing 2％ fetal bovine serum (FBS).Different concentrations of SFN (0,1,10 and 100 μ mol) were added in the medium for 30 days respectively according to grouping,and the growth of LECs was observed by optical microscope and immunofluorescence technique.FHL124,a human LEC line,was cultured with EMEM containing 5％ FBS and divided into 0,1,10,30 and 100 μmol SFN groups.Lactate dehydrogenase (LDH) release rate in the medium was detected to evaluate cell damage/death.The migration of the cells on capsular bags was assessed by scratch test.The ultrastructure and number of autophagosomes were examined under the transmission electron microscope.The expression of LC3 in the cells were detected using Western blot in the presence or absence of autophagy inhibitors.Results The cell coverage rates on the capsular bags were significantly lower in the 10 and 100 μ mol/L SFN groups than those in the 0 and 1 μmol/L SFN groups,with a statistically significant difference among the groups (F =48.57,P ＜ 0.01).Immunofluorescence showed that the density of F-actin-and Vimentin-positive cells was evidently decreased in the 10 and 100 μmol/L SFN groups compared with 0 and 1 μ mol/L SFN groups.The releasing levels of LDH (absorbancy) were 0.19± 0.03,0.39±0.06,0.56±0.07,0.68±0.08 and 0.89±0.09 in the 0,1,10,30 and 100 μ mol/L SFN groups,respectively,and the releasing level of LDH was gradually increased in the 10 and 100 μ mol/L SFN groups in comparison with the 1 μmol/LSFN group (all at P＜0.01).With the increase of SFN concentration,the reduction rate of scratched area decreased with the increase of SFN concentration,and the decrease of scratch area was significantly lower than that of adjacent low mass concentration group and the differences were statistically significant (P＜0.05).The relative expressions of LC3-Ⅱ protein were 0.423±0.003,14.543±0.024,0.668±0.024 and 0.576±0.056 in the blank control group,SFN group,SFN + 3-MA group and 3-MA group,respectively,and the relative expressions of LC3-Ⅱ protein were significantly lower in the SFN+3-MA group and 3-MA group than those in the SFN group (all at P＜0.01).The number of autophagosomes was 4.07±0.32,4.13±0.34,9.21 ±0.53 and 21.02± 1.34 in the blank control group,and 1,10,100 μmol/L SFN groups,and the number of autophagosomes in the 10 and 100 μ mol/L SFN groups was significantly higher than that in the blank control group and 1 μmol/L SFN group (all at P＜0.01).Conclusions SFN mediates LECs death by promoting autophagy in ex vivo capsular bags,and SFN may be a novel agent of potential chemopreventive and target treatment for PCO.

Micro-CT evaluating inhibitory effect of zoledronic acid on polyethylene particle-induced periprosthetic osteolysis model / 中国骨伤

<p><b>OBJECTIVE</b>To observe inhibitory effect of zoledronic acid on polyethylene particle-induced periprosthetic osteolysis model.</p><p><b>METHODS</b>Thirty male adult specific-pathogen-free SD rats (weighted 250 to 300 g) were randomly divided into sham group, model group, and zoledronic acid group, 10 in each group. Modeling were building by titanium screws and polyethylene particles implanted into right femur of rats, sham group and model group were performed hypodermic injection by 0.9% saline with 2 ml/kg, zoledronic acid with 0.1 ml/mg were injected into zoledronic acid group, once a week for 8 weeks. After 8 weeks, right femur specimens were drawn and used to san microstructure of femoral cancellous bone in rats model was examined by Micro-CT, and the images were treated with three-dimension reconstruction and analysis software BMD, BV/TV, Tb.N, Tb.Th, SMI, BS/BV, Tb.Sp and Tb.Pf and other parameters include.</p><p><b>RESULTS</b>According to Micro-CT three-dimensional imaging, BMD in model group was significantly decreased than sham group, bone microstructure damage was serious, bone trabecula changed thinning continuity; while bone microstructure was obviously improved compared with model group and zoledronic acid group. After analyzing Micro-CT parameters of femur microstructure, BMD in model group(0.081±0.020) was significantly decreased than control group(0.160±0.018) and zoledronic acid group(0.125±0.012); BV/TV in model group (10.563±1.070) was obviously lower than control group(27.935±1.834) and zoledronic acid group(14.559±1.258); Tb.N in model group (1.005±0.165) was lower than control group(2.058±0.108) and zoledronic acid group(1.515±0.126); while Tb.Th in model group (0.075±0.016) was decreased than control group(0.158±0.016) and zoledronic acid group(0.124±0.011). Meanwhile, SMI in model group(1.817±0.127) was significantly higher than control group(1.104±0.120) and zoledronic acid group(1.547±0.122); BS/BV in model group(35.784±1.650) was higher than control group(21.506±2.771) and zoledronic acid group(30.399±2.730); Tb.Sp in model group(0.735±0.107) was higher than control group(0.423±0.057) and zoledronic acid group(0.577±0.082), TB.Pf in model group(9.088±1.283) was higher than control group(2.447±0.703) and zoledronic acid group(5.862±1.042).</p><p><b>CONCLUSIONS</b>Zoledronic acid could change bone microstructure of rats to inhibit polyethylene particle-induced bone solution, which provides a scientific basis for prevent bone solution by zoledronic acid as a therapeutic intervention.</p>

Hepatocyte autophagy model established by physical method / 临床肝胆病杂志

ObjectiveTo establish the autophagy model of normal human liver cell line 7702 induced by hypoxia and starvation, and to lay a foundation for further studies on the influence of autophagy on liver function. MethodsThe 7702 cells were selected and incubated with 95% air and 5% CO2 at a temperature of 37 ℃(normal control group). The Binder three-gas incubator was used, with a temperature of 37 ℃, a CO2 concentration of 5%, and an O2 concentration of 0.3% to provide a hypoxic environment, and the serum-free DMEM was used to induce starvation. These cells were divided into 6-, 12-, 18-, and 24-hour hypoxia-starvation groups. Western blot was used to measure the protein expression of Beclin 1, Atg5, and LC3 in the normal control group and experimental groups, RT-qPCR was used to measure the mRNA expression of Beclin 1 and Atg5 in each group, and after transfection of LC3 plasmid, immunofluorescence assay was used to observe autophagy in each group. An analysis of variance was used for comparison of continuous data between groups, and the least significant difference t-test was used for further comparison between any two groups; the chi-square test was used for comparison of categorical data between groups. ResultsThe 6-hour hypoxia-starvation groups had higher protein expression of Beclin 1, Atg5, and LC3 than the normal control group or other treated groups. Compared with all the other groups, the 6-hour hypoxia-starvation group showed significantly increased mRNA expression of Beclin 1 and Atg5, as well as significantly greater increases in the mRNA expression of Beclin 1 and Atg5 (all P＜0.05). The hypoxia-starvation groups had significantly lower numbers of autophagosomes than the normal control group, and the 6-hour hypoxia-starvation group had the highest number of autophagosomes (all P＜0.05). ConclusionHypoxia and starvation established by physical methods can successfully induce hepatocyte autophagy, which is the most remarkable at 6 hours of hypoxia and starvation.

Stress distribution and deformation of uterosacral ligament and cardinal ligament under different working conditions simulated by the finite element model / 中华妇产科杂志

Objective To establish the finite element model of uterosacral ligament (USL) and cardinal ligament (CL) and analyze the stress distribution and deformation with USL and CL under different working conditions. Methods Patients with stage Ⅲ-Ⅳpelvic organ prolapse (POP) and healthy female volunteers were selected for research subject, and divided into anterior uterus group and posterior uterus group. Two POP patients and two volunteers were selectd into the anterior uterus group and posterior uterine group respectively. Pelvic MRI scan was performed in two groups. Based on the original MRI data sets, the finite element model of USL and CL was constructed by using the software such as the Mimics, and the stress distribution and deformation of USL and CL were simulated. Results Under the premise of the elastic modulus fixed and three different working conditions such as 60 cmH2O, 99 cmH2O and 168 cmH2O (1 cmH2O=0.098 kPa) with abdominal pressure generated by maximum Valsalva maneuver, according to the present conditions and the simulation, the trend was analyzed: the stress and deformation of the uterus, anterior vaginal wall, USL and CL in two groups were mainly distributed in the middle and lower part of the anterior vaginal wall or the ligament and the cervix-vagina junction, the maximum stress and the maximum displacement were mainly concentrated in the lower region of the anterior vaginal wall. With increasing of abdominal pressure generated by the maximum Valsalva maneuver, the maximum stress values of the POP patient in anterior uterus group under three different working conditions were: 0.027 9, 0.046 0, 0.078 0 MPa, and the maximum displacement values were: 9.145 5, 15.090 0, 25.607 0 mm. The maximum stress values of the volunteer in anterior uterus group under three different working conditions were:0.012 6, 0.020 8, 0.035 3 MPa, and the maximum displacement values were: 1.816 7, 2.997 5, 5.086 7 mm. The maximum stress values of the POP patient in posterior uterine group under three different conditions were: 0.069 4, 0.114 6, 0.194 5 MPa, and the maximum displacement values were:11.658 0, 19.236 0, 32.643 0 mm. The maximum stress values of the volunteer in posterior uterus group under three different working conditions were:0.009 1, 0.015 1, 0.025 6 MPa, and the maximum displacement values were:2.581 6, 4.259 6, 7.228 4 mm. The maximum stress values and the maximum displacement values were all increased with increasing of abdominal pressure in the two groups. The maximum stress values and the maximum displacement values of the POP patients were greater than those of volunteers. Under different working conditions, the maximum stress values and maximum displacement values of the posterior uterus POP patient were all greater than those of the anterior uterus POP patient. Conclusions The finite element model of USL and CL is completely based on the MRI technology and the model is real and reliable. The increase of abdominal pressure will produce a larger stress and deformation of USL and CL, which is one of the reasons causing the injury of the ligament.

Spatial distribution of pregnancy in adolescence and associations with socioeconomic and social responsibility indicators: State of Minas Gerais, Southeast of Brazil / Distribuição espacial da gravidez adolescente e associações com indicadores socioeconômicos e de responsabilidade social: estado de Minas Gerais, sudeste do Brasil

To describe associations between pregnancy rates in adolescence and socioeconomic and social responsibility indicators in the municipalities of the State of Minas Gerais, Southeast of Brazil, in the year of 2010.

Descrever as associações entre os percentuais de gravidez na adolescência e indicadores socioeconômicos e de responsabilidade social dos municípios do estado de Minas Gerais, sudeste do Brasil, no ano de 2010.

An inexpensive yet realistic model for teaching vasectomy

Purpose Teaching the no-scalpel vasectomy is important, since vasectomy is a safe, simple, and cost-effective method of contraception. This minimally invasive vasectomy technique involves delivering the vas through the skin with specialized tools. This technique is associated with fewer complications than the traditional incisional vasectomy (1). One of the most challenging steps is the delivery of the vas through a small puncture in the scrotal skin, and there is a need for a realistic and inexpensive scrotal model for beginning learners to practice this step. Materials and Methods After careful observation using several scrotal models while teaching residents and senior trainees, we developed a simplified scrotal model that uses only three components–bicycle inner tube, latex tubing, and a Penrose drain. Results This model is remarkably realistic and allows learners to practice a challenging step in the no-scalpel vasectomy. The low cost and simple construction of the model allows wide dissemination of training in this important technique. Conclusions We propose a simple, inexpensive model that will enable learners to master the hand movements involved in delivering the vas through the skin while mitigating the risks of learning on patients. .

A biomechanical model of knee osteoarthritis and stress characteristics on the cartilage surface / 中国组织工程研究

BACKGROUND:Knee osteoarthritis is a chronic disease characterized as cartilage degeneration and hyperostosis to impact the soft tissues around the joints, thereby resulting in joint pain, and it can be aggravated and lead to joint deformity after weight-bearing. OBJECTIVE:On the basis of imaging parameters of knee osteoarthritis patients and normal controls, a model was established. And then, knee squatting movement was simulated on the model and stress data from the cartilage surface of patients and normal controls were colected and compared, thereby to obtain the stress characteristics of the cartilage surface in knee osteoarthritis patients. METHODS: There were 30 knee osteoarthritis patients and 30 healthy volunteers in the study. CT and MRI data from these participants were colected and analyzed using Mimics software and simpleware software to establish a model. Based on this model, cartilage-related stress data were harvested from knee osteoarthritis patients and healthy volunteers and compared to summarize the stress characteristics of the articular cartilage in patients with knee osteoarthritis. RESULTS AND CONCLUSION:In knee osteoarthritis patients, the stress on the cartilage surface from standing to squatting was increased in a nonlinear manner. During the process of squatting, the mediolateral stress was higher in the knee osteoarthritis patients than healthy controls (P 0.05). These findings indicate that the knee osteoarthritis musculoskeletal model and finite element model are established successfuly, and these models are closer to the real motion characteristics of the knee joints, based on which, quantitative biomechanical data of the knee can be provided for knee osteoarthritis treatment.

Dynamic expression of interleukin-22 in grafts after allograft corneal transplantation and its relationship with graft rejection in rats / 中华实验眼科杂志

Background The rejection following keratoplasty still is a leading cause of corneal transplantation failure.Studies showed that the interleukin-22 (IL-22) ,one of the effector molecules of T helper cell 17 (Th17) participated on the rejection after heart,liver and bone marrow transplantation.However,the effect of IL-22 on corneal graft rejection is not well understood.Objective This study was to investigate the expression of IL-22 mRNA in the corneal grafts and the role of IL-22 in the immune rejection after corneal transplantation in rats.Methods Seventy-two Wistar rats were randomized into autologous keratoplasty group,allograft keratoplasty group and anti-rejection group,and other 4 normal Wistar rats served as normal control group.Autologous keratoplasty was operated on the Wistar rats of the autologous keratoplasty group,and allograft keratoplasty were carried out with the 24 SD rats as donors and 48 Wistar rats as recipients.Tobramycin and dexamethasone eye drops were topically administrated after autologous keratoplasty for 2 weeks in the anti-rejection group.The experimental eyes were examined by slit lamp microscope after surgery and graft survival was evaluated based on the rejection scoring criteria of Larkin.Intergroup accumulated survival rates of grafts were compared using Kaplan-Meier analysis.Histopathological examination of grafts was carried out in 5 and 14 days after operation respectively,and the related expression levels of IL-22 mRNA and aryl hydrocar-bon receptor (AhR) mRNA were carried out by real-time fluorescence quantitative PCR.The feeding and use of the experimental animals followed the Guangdong provincial regulations on the management of experimental animals.The experimental design was approved by the ethics committee of Southern Medical University.Results The median survival time of grafts in the allograft keratoplasty group was 10 days,and that in the anti-rejection group was 17 days,showing a significant survival extention in the anti-rejection group (x2=16.442,P =0.000).Significant differences were found among the 4 groups in the related expression levels of IL-22 mRNA in both 5 days and 14 days after surgery (postoperative 5 days : F=2.44,P =0.00;postoperative 14 days: F=267.92, P =0.00), and the related expression levels of IL-22 mRNA were remarkably higher in the allograft keratoplasty group than those in the anti-rejection group at different time points (postoperative 5 days :9.70±0.35 vs.0.46±0.21;postoperative 14 days : 23.12 ± 1.89 vs.3.14±0.94) (both at P＜0.05).The related expression levels of AhR mRNA in the grafts were considerably different among the 4 groups (postoperative 5 days : F =395.73, P =0.00;postoperative 14 days : F =942.37, P =0.00) , and the expression levels were significantly elevated in the allograft keratoplasty group compared with the anti-rejection group at various time points (postoperative 5 days:2.52±0.32 vs.1.89±0.10;postoperative 14 days:7.20±0.25 vs.2.60±0.17) (both at P＜0.05).Conclusions The expression level of IL-22 RNA up-regulates in the grafts with immuno-rejection.Topical administration of tobramycin and dexamethasone eye drops inhibits the rejection after keratoplasty.AhR plays a regulative role to the expression of IL-22 in rats after keratoplasty.

Valoración terapéutica del agua de mar en modelos experimentales como terapia complementaria en anemia / Valuation therapeutic seawater in experimental models as complementary therapy in anaemia

Introducción: la anemia es un problema de salud pública a nivel mundial, según la Organización Mundial de la Salud afecta en todo el mundo a 1620 millones de personas. En América Latina y el Caribe el 31% de la población presenta problemas de anemia asociadas a dietas deficientes de hierro y relacionadas con malnutrición. Objetivo: evaluar los efectos terapéuticos del agua de mar isotónica microfiltrada al frío como terapia complementaria en modelos biológicos con anemia inducida experimentalmente por dietas pobres en proteínas, vitaminas y minerales, y por medicamentos. Materiales y métodos: se contó durante ocho semanas con 50 ratones cepas NMRI, de ambos géneros y en edad adulto-joven. Se dividieron en cuatro grupos experimentales de 10 ratones cada uno, incluyendo un grupo control. Fueron evaluados al inicio y final del experimento los parámetros hematológicos, pH salival, cobre y zinc. Al final del experimento fueron sacrificados por dislocación cervical y autopsiados para examinar bazo, hígado y riñón. Resultados: los modelos experimentales bajo ingesta de agua de mar con relación al grupo sin agua de mar, independiente del tipo de anemia inducida, evidenciaron diferencias estadísticamente significativas (p< 0,05) con restablecimiento de los parámetros hematológicos. El bazo se observó en tamaño y condiciones normales evidenciando restablecimiento del daño inmunológico ocasionado. Órganos como riñón e hígado no mostraron daños morfológicos. Conclusiones: el agua de mar isotónica resultó útil como terapia complementaria en los modelos experimentales, en casos de anemias causadas por dietas pobres en proteínas, vitaminas y minerales, y desencadenadas por medicamentos. MÉD.UIS. 2014;27(3):9-18.

Introduction: the anaemia is a major public health worldwide, according to the World Health Organization worldwide affects 1620 million people in Latin America and the Caribbean 31% of the population has problems anemia's associated with deficient diets iron and related malnutrition. Objective: evaluating those therapeutic effects of isotonic seawater microfiltered to cold as complementary therapy in biological models with experimentally induced anaemia by poor diets in protein, vitamins and minerals, and by medicaments. Materials and Methods: they counted for eight weeks with 50 NMRI mice of both genders, adult - young age. Were divided into four experimental groups of 10 mice each, including a control group. Evaluated to the beginning and end of the experiment were the hematological parameters, salivary pH, copper and zinc. At the end of the experiment they were sacrificed by cervical dislocation and autopsied stops examine spleen, liver and kidney. Results: the experimental models under seawater intake relative to the group without sea water, independent of the type of induced anaemia, showed statistically significant differences (p < 0.05) with restoration of hematological parameters. The spleen was observed in size and showing restoration of normal immune damage caused. Organs such as kidney and liver showed no morphological damage. Conclusions: isotonic seawater useful as complementary therapy in experimental models, in cases of anemia caused by diets low in protein, vitamins and minerals, and triggered by medicament. MÉD. UIS. 2014;27(3):9-18.

Finite element modelling of cornea mechanics: a review / Modelagem de elementos finitos da mecânica da córnea: uma revisão

The cornea is a transparent tissue in front of the eye that refracts light and facilitates vision. A slight change in the geometry of the cornea remarkably affects the optical power. Because of this sensitivity, biomechanical study of the cornea can reveal much about its performance and function. In vivo and in vitro studies have been conducted to investigate the mechanics of the cornea and determine its characteristics. Numerical techniques such as the finite element method (FEM) have been extensively implemented as effective and noninvasive methods for analyzing corneal mechanics and possible disorders. This article reviews the use of FEM for assessing the mechanical behavior of the cornea. Different applications of FEM in corneal disease studies, surgical predictions, impact simulations, and clinical applications have been reviewed. Some suggestions for the future of this type of modeling in the area of corneal mechanics are also discussed.

A córnea é um tecido transparente na parte frontal do olho, que refrata a luz e torna a visão possível. Uma ligeira alteração na geometria da córnea notavelmente afeta a sua potência óptica. Devido a essa sensibilidade, o estudo biomecânico da córnea pode revelar muito sobre o seu desempenho e funcionalidade. Estudos in vivo e in vitro foram realizados para investigar a mecânica da córnea e para determinar suas características. Técnicas numéricas como o método dos elementos finitos (FEM) foram amplamente implementadas como métodos eficazes e não invasivos de análise mecânica da córnea e seus possíveis transtornos. Este artigo analisa o uso de FEM para avaliar o comportamento mecânico da córnea. Diferentes aplicações da FEM no estudo de doenças da córnea, previsões cirúrgicas, simulações de impacto e aplicações clínicas foram revistos. São discutidas algumas sugestões para o futuro deste tipo de modelagem na área de mecânica de córnea.

Influence of local or systemic corticosteroids on skin wound healing resistance / Influência de corticosteróide local e sistêmico no processo cicatricial cutâneo

PURPOSE: To compare the resistance of skin wound healing of mice submitted to local or systemic hydrocortisone administration, in different postoperative periods. METHODS: An incision and suture was performed on the thoracic skin of 130 male mice: Group 1 (n = 10) resistance of the integer skin; Group 2 (n = 30) submitted only to skin incision and suture; Group 3 (n = 30) skin incision and suture followed by administration of saline fluid; Group 4 (n = 30) skin incision and suture followed by administration of local hydrocortisone; Group 5 (n = 30) skin incision and suture followed by administration of systemic hydrocortisone. The resistance of the wound healing and the weight of the animals were studied on the seventh, 14th and 21st postoperative days. Histological examination was also performed. RESULTS: The mice that received corticoid (groups 4 and 5) presented significant decreasing on their weight (p = 0.02). The Groups 3, 4 and 5 showed lower scar resistance than Group 2 on the seventh postoperative day (p < 0.05). On the 14th and 21st days, there was no difference on the skin would healing resistance (p > 0.05). CONCLUSION: Administration of hydrocortisone in mice is responsible for weight decreasing and reduction of the skin wound healing resistance during the first postoperative week.

OBJETIVO: Comparar a resistência cicatricial cutânea de camundongos submetidos a administração de hidrocortisona por diferentes vias e em distintos períodos pós-operatórios. MÉTODOS: Foram estudados 130 camundongos machos submetidos à incisão e sutura de pele da região dorsal do tórax: Grupo 1 (n = 10) resistência da pele íntegra; Grupo 2 (n = 30) incisão da pele e sutura, sem administração de corticóide; Grupo 3 (n = 30) incisão da pele e sutura, seguidas de injeção local de solução salina; Grupo 4 (n = 30) incisão da pele e sutura, seguidas de injeção local de hidrocortisona e Grupo 5 (n = 30) incisão da pele e sutura, seguidas de injeção intraperitoneal de hidrocortisona. Foram avaliadas a resistência cicatricial da pele e a variação ponderal no sétimo, 14º e 21º dias pós-operatórios, bem como sua histologia. RESULTADOS: Os camundongos que receberam hidrocortisona tiveram decréscimo ponderal (p = 0,02). Quanto à resistência cicatricial da pele, os Grupos 3, 4 e 5 apresentaram valor inferior ao Grupo 2, no sétimo dia pós-operatório (p = 0,031). No 14º e 21º dias, não houve diferença entre as tensões cicatriciais. CONCLUSÃO: A administração de hidrocortisona provoca redução ponderal em camundongos e a resistência cicatricial cutânea é menor na primeira semana pós-operatória.

Establishment of damaged endometrial stromal cells model in vitro / 中华妇产科杂志

ObjectiveTo investigate the method of establishing damaged endometrial stromal cells (ESC) model in vitro.Methods ( 1 ) From June to December 2011 ESC from normal endometrim at proliferation phase ( n =8 ) and secretory phase ( n =8 ) were isolated,cultured and identified in vitro.( 2 ) ESC was treated with different concentrations of mifepristone or withdrawal of mifepristone at different time point.The proliferation inhibition percent was measured by cell counting kit-8 ( CCK-8 ). ( 3 ) 0 μmol/L (control group)and 60 μmol/L(experimental group) concentration of mifepristone was added into ESC for 48 hours,then withdrew of mifepristone,continued to be cultured for 48 hours.The morphological changes were observed and apoptosis of ESC in different menstrual cycle were detected by flow cytometry.The mRNA and protein level of vascular endothelial growth factor ( VEGF),caspase-3,8,and 9 were determined by one-step quantitative real-time PCR (Q-PCR) and western blot.Results( 1 ) ESC from 16 specimens of endometrium were all isolated and cultured successfully. (2) The proliferation inhibition rate of ESC was correlated with concentration and duration of mifepristone positively. The proliferation of ESC could be recovered at a range of time after withdrawal of mifepristone.However,when the concentration of mifepristone was 100 μmol/L,the growth of ESC recovered very hardly. (3) The damaged ESC spacing increased,the spindle shape and vacuolization in the cytoplasm were observed in experimental group; the rate of apoptosis of these damaged cells was significantly increased compared with control groups,which were (52 ± 12)％ vs.( 13 ± 5 ) ％ at the proliferative phase and (53 ± 6) ％ vs.( 32 ± 3 ) ％ at the secretory phase ( all P ＜0.05).The relative mRNA level of VEGF was 0.52± 0.12 in experimental group and 1.00 ± 0.17 in control group at proliferation phase (P ＜0.05).And the relative mRNA level of VEGF was 0.19 ±0.03 in experimental group and 0.81 ±0.07 in control group at secretory phase (P ＜ 0.05).The relative level of VEGF protein in the experimental group were both decreased 1.98 and 2.79 folds at the proliferation phase and the secretory phase when compared with those in control group,respectively ( P ＜ 0.05 ).While the relative levels of caspase-3,8,9 mRNA were 5.62 ± 0.65,5.41 ± 0.53,7.22 ± 0.51 in the experimental group and 1.00 ± 0.44,1.00 ± 0.21,1.00 ± 0.32 in control group at the proliferative phase.In the mean time,the relative levels of caspase-3,8,9 mRNA were 10.22 ± 0.72,25.3 ± 1.72,9.48 ± 1.89 in experimental group and 1.42 ± 0.14,1.14 ± 0.28,1.16 ± 0.12 in control group at the secretory phase,respectively (P ＜ 0.05).Compared with the control group,the levels of caspase protein in the experimental group were increased 2.04 and 1.60 folds in caspase-3,4.23 and 1.49 folds in caspase-8,2.65 and 3.5 folds in caspase-9 at the proliferative phase and at the secretory phase,respectively (P ＜ 0.05 ).ConclusionThe damaged model of ESC can be established after 48 hours by the withdrawal of 60 μmol/L mifepristone in treatment of ESC for 48 hours.

Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery

The generation of disease-specific induced pluripotent stem cell (iPSC) lines from patients with incurable diseases is a promising approach for studying disease mechanisms and drug screening. Such innovation enables to obtain autologous cell sources in regenerative medicine. Herein, we report the generation and characterization of iPSCs from fibroblasts of patients with sporadic or familial diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), juvenile-onset, type I diabetes mellitus (JDM), and Duchenne type muscular dystrophy (DMD), as well as from normal human fibroblasts (WT). As an example to modeling disease using disease-specific iPSCs, we also discuss the previously established childhood cerebral adrenoleukodystrophy (CCALD)- and adrenomyeloneuropathy (AMN)-iPSCs by our group. Through DNA fingerprinting analysis, the origins of generated disease-specific iPSC lines were identified. Each iPSC line exhibited an intense alkaline phosphatase activity, expression of pluripotent markers, and the potential to differentiate into all three embryonic germ layers: the ectoderm, endoderm, and mesoderm. Expression of endogenous pluripotent markers and downregulation of retrovirus-delivered transgenes [OCT4 (POU5F1), SOX2, KLF4, and c-MYC] were observed in the generated iPSCs. Collectively, our results demonstrated that disease-specific iPSC lines characteristically resembled hESC lines. Furthermore, we were able to differentiate PD-iPSCs, one of the disease-specific-iPSC lines we generated, into dopaminergic (DA) neurons, the cell type mostly affected by PD. These PD-specific DA neurons along with other examples of cell models derived from disease-specific iPSCs would provide a powerful platform for examining the pathophysiology of relevant diseases at the cellular and molecular levels and for developing new drugs and therapeutic regimens.

Further understanding of fat biology: Lessons from a fat fly

Obesity is a leading risk factor for insulin resistance, hypertension, hyperlipidemia, and cardiovascular complications, collectively referred to as metabolic diseases. Given the prevalence of obesity and its associated medical problems, new strategies are required to prevent or treat obesity and obesity-related metabolic effects. Here we summarize contributors of obesity, and molecular mechanisms controlling adipogenesis from studies in mammalian systems. We also discuss the possibilities of using Drosophila as a genetic model system to advance our understanding of players in fat biology.

Establishment of an in vitro model of brain-blood barrier / 北京大学学报(医学版)

Objective: To establish an in vitro model of brain blood barrier (BBB) using cultured mouse brain microvascular endothelial cells (BMVEC). Methods: Mouse BMVEC were seeded on micro pore membrane of gelatin coated cell culture insert and cultured to confluence. The establishment of BBB was preliminary judged by a 4 h water leaking test. The tight junctions between BMVEC were demonstrated by scanning and transmission electron microscope. The transendothelial electrical resistance(TEER) over BMVEC was measured. The permeability of Horseradish peroxidase (HRP) through the BBB was analyzed and the effect of RMP 7 on permeability of the BBB was investigated. Results: The 4 h water leaking test became positive when BMVEC were cultured to confluence. By scanning and transmission electron microscope, the tight junctions were demonstrated on confluent BMVEC. The TEER over BMVEC monolayer increased 3.2 and 7.68 times and the permeability rates for HRP were 13.4% and 6.7% respectively, as compared with sub confluent BMVEC and human umbilical vein endothelial cell monolayer(HUVEC). The HRP permeability rate in the model of BBB increased 2.7 times after treatment with RMP 7. Conclusion: The established in vitro model of BBB has basic characteristics of BBB in vivo , and is suitable for central nervous system (CNS) drug research over BBB.

Establishment of artificial lumbar intervertebral disc three-dimensional finite element and its stress analysis / 中华骨科杂志

Objective To study artificial lumbar intervertebral disc three-dimensional finite element model and its stress state. Methods The three-dimensional finite element models of artificial lumbar intervertebral disc were established by finite element software MSC. MARK. While L4-5 motion segment from young healthy cadaver was created to give the models biomaterial characters. The vertebral disc of L4-5 was replaced by artificial lumbar intervertebral disc to make a model of an artificial disc replacement. Results After three-dimensional finite element models with biomaterial characters of artificial lumbar intervertebral disc and L4-5 motion segment had been created, the stress distribution of artificial lumbar intervertebral disc showed some characteristics as follows:1)The stress exerted in the center of polyethylene slide core and end plates is biggest in all motion states, the next exists at the deviated site while the polyethylene slide core set in motion. 2)The upper surface of polyethylene slide core and end plates bear 2-3 times stress as much as that of the lower surface. 3)The biggest stress exists in the center of polyethylene slide core and end plates during compression in all motion states. Conclusion Establishment of three-dimensional finite element models of artificial lumbar intervertebral disc and analysis of its stress are feasible. The results are reliable.