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OBJECTIVE@#To assess acute toxicity, the in vitro and in vivo effects of methanol and ethyl acetate extracts (JME and JEE) of Jatonik polyherbal mixture on some mitochondria-related parameters and their effect on the activity of some liver enzymes.@*METHODS@#Acute toxicity of JME and JEE was determined using Lorke's method. In vitro and in vivo opening of the mitochondrial membrane permeability transition pore (MMPT pore) was spectrophotometrically assayed. Production of malondialdehyde (MDA) as an index of lipid peroxidation and the activity of mitochondrial ATPase was evaluated in vitro and in vivo and the effect of JME and JEE on the activity of liver enzymes such as alkaline phosphatase (ALP), aspartate and alanine aminotransferase (AST and ALT) and gamma-glutamyl transferase (GGT) was also investigated.@*RESULTS@#JME had an LD50 of 3 808 mg/kg b.w whereas JEE had an LD50 greater than 5 000 mg/kg b.w. of rats. After the rats have been fed with both extracts, a photomicrograph of a piece of liver tissue showed no apparent symptoms of toxicity. From the in vitro and in vivo studies, both extracts prompted intact mitochondria to open their MMPT pores. When compared to the control, lipid peroxide product release and ATPase activity were significantly increased (P < 0.05) in vitro and in vivo. The activities of AST, ALT, and GGT were all reduced at 50 mg/kg when treated with JME, but the activity of AST was considerably enhanced when treated with JEE (P < 0.05). The results revealed that both JME and JEE of the Jatonik polyherbal mixture had low toxicity, profound MMPTpore induction, and enhanced ATPase activity, but an increased MDA production.@*CONCLUSION@#Jatonik extracts may be a promising target for drug development in diseases where there is dysregulation of apoptosis, however, further studies are needed to better clarify the molecular mechanism involved in these phenomena.
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Objective To prepare polymersomes (PSs) by block copolymers,evaluate their membrane structural stability,investigate the H+ transmembrane permeability of PSs and the impact of 1,4-dioxane and establish a foundation for drug encapsulation within polymersomes. Methods PSs were self-assembled by a block copolymer, PEG-PLGA, in a solvent solution. The pH-sensitive fluorescence probe HPTS was employed to examine the H+ transmembrane properties of PSs and compare them with PSs prepared using PBD-b-PEO, PS-b-PEO, and liposomes. The effect of varying concentrations of 1,4-dioxane on PSs’ membrane permeability properties was also investigated. Results The fluorescence excitation spectra of HPTS exhibited pH dependency, which showed a linear correlation between extravesicular H+ concentration and t1/2. Significant differences were observed in the membrane permeability capabilities of PSs with different membrane wall thicknesses. Compared to liposomes, the H+ transmembrane coefficients for the three types of PSs were reduced by 2.39×104, 3.38×104, and 5.48×108 times, respectively. 1,4-dioxane was found to modulate the permeability of PSs’ membranes, which displayed a concentration-dependent relationship. Conclusion PSs exhibited significantly lower membrane permeability compared to liposomes, indicating superior stability. 1,4-dioxane was identified as a modulator of PSs’ permeability, which offered potential for drug loading and release within PSs.
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Tumor cells use glycolysis to provide material and energy under hypoxic conditions to meet the energy requirements for rapid growth and proliferation, namely the Warburg effect. Even under aerobic conditions, tumor cells mainly rely on glycolysis to provide energy. Therefore, glucose transporter protein 1(GLUT1), which is involved in the process of glucose metabolism, plays an important role in tumorigenesis, development and drug resistance, and is considered to be one of the important targets in the treatment of malignant tumors. In recent years, research on tumor glucose metabolism has gradually become a hot spot. It has been shown that various factors are involved in the regulation of tumor energy metabolism, among which the role of GLUT1 is the most critical. In this paper, the authors reviewed the latest research progress of GLUT1-targeted traditional Chinese medicine(TCM) active ingredient nano-delivery system in tumor therapy, aiming to reveal the feasibility and effectiveness of this system in the delivery of chemotherapeutic drugs. The GLUT1-targeted TCM active ingredient nano-delivery system can overcome the bottleneck of the traditional targeting strategy as well as the high-permeability long retention(EPR) effect. In summary, the authors believe that the GLUT1-targeted TCM active ingredient nano-delivery system provides a new strategy for targeted treatment of tumors and has a broad application prospect in tumor prevention and treatment.
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@#Objective To investigate the correlation between heparin-binding protein(HBP)and vascular permeability in patients with sepsis.Methods Four hundred infected patients admitted to Affiliated Jinhua Hospital Zhejiang University School of Medicine from November 2019 to November 2022 were retrospectively selected and divided into sepsis group(n=190)and non-sepsis group(n=210)according to whether they were diagnosed with sepsis or not.HBP,the difference between hematocrit(HCT)and serum albumin(ALB)(HCT-ALB)and percentage of fluid overload were compared between two groups.Pearson method was used to analyze the correlation between HBP,HCT-ALB and percentage of liquid overload.Results HBP,HCT-ALB and percentages of fluid overload in sepsis group were significantly higher than those in non-sepsis group(P<0.05).Pearson correlation analysis showed that serum HBP level was positively correlated with HCT-ALB and percentage of fluid overload 24h after admission(P<0.05).Conclusion Increased vascular permeability in patients with sepsis may be related to the high level of HBP released by neutrophils stimulated by bacterial toxins.
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In patients with acute ischemic stroke, there is a wide variation in the composition of blood clots that block the blood vessels. Some imaging features are associated with the components of the clot, such as thrombus permeability, which is related to higher red blood cell density and lower fibrinogen density. The different components and mechanical properties of the clot may have an impact on treatment effectiveness and risk. Therefore, this article aims to summarize the correlation between thrombus permeability and biological, imaging characteristics, and explore the clinical significance of thrombus permeability in the treatment of patients with acute ischemic stroke, providing reference and assistance for neurologists.
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With the increasing prevalence of diabetes, the prevention and treatment of diabetes nephropathy have become a worldwide problem. The molecular mechanism of the occurrence and development of diabetes nephropathy is still unclear, but many studies in recent years have shown that gut microbiota plays an important role in the progress on diabetes nephropathy. The research progress on the mechanism of gut microbiota participating in diabetes nephropathy was reviewed in this article.
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BACKGROUND:With the increasing number of tendon transplantation surgeries for tendon injuries,the demand for tendon tissue engineering scaffolds is increasing.Research has found that good pore size and porosity of implants contribute to tissue healing. OBJECTIVE:To review the types of materials currently published for tendon tissue engineering scaffolds and investigate the correlation between various tendon tissue engineering scaffold materials and pores. METHODS:Articles were retrieved on PubMed,Embase,and Web of Science databases,using keywords"tendon"or"ligament"and"tissue scaffold"as well as"porosity"or"permeability".A total of 84 articles meeting the criteria were included to summarize,discuss and anticipate future development directions. RESULTS AND CONCLUSION:The materials used in the research of tendon tissue engineering are mainly divided into two categories:natural tendon scaffold materials and artificial synthetic tendon scaffold materials.Natural scaffold materials include autologous tendons,allogeneic tendons,and xenogeneic tendons.Autogenous tendons and allogeneic tendons have been used in clinical practice for many years.During the preparation of allogeneic tendons and animal experiments,it was found that the process of acellular disinfection resulted in an increase in the pore size and porosity of both types of tendons,but the specific reasons and mechanisms have not been further studied.There are many types of artificial tendon scaffold materials currently being studied,among which artificial ligament products such as Leeds Keio and LARS(Ligament Advanced Reinforcement System)are still in use in some countries.Other materials have not been promoted in clinical practice due to immature technology and other issues.The pores and porosity of artificial tendon scaffold materials also show different trends due to their different materials and preparation techniques.
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BACKGROUND:The relationship between insulin resistance and intestinal mucosal permeability may be related to excess fat,inflammation and oxidative stress.At present,the influence of different kinds of exercise on this relationship has not been fully studied,and the relevant mechanism needs to be further studied. OBJECTIVE:To study the effects of continuous exercise and cumulative exercise on intestinal mucosal permeability of insulin-resistant mice induced by high fat diet,and to compare the effects of different intensities of exercise,thereby evaluating the health-promoting effects of cumulative exercise. METHODS:Four-week-old male C57BL/6J mice were fed high-fat diet to induce insulin resistance,and mice with successful modeling were randomly divided into five groups:high-fat insulin resistance group,general dietary insulin resistance group,moderate-intensity continuous exercise group,moderate-intensity cumulative exercise group,and high-intensity cumulative exercise group.Mice in the high-fat insulin resistance group received high-fat diet and mice in the other groups were fed normally.All the exercise groups received 8 weeks of different forms of treadmill training.Mice in the moderate-intensity sustained exercise group exercised for 50 minutes at a speed of 11 m/min.Mice in the moderate-intensity cumulative exercise group were subjected to 12.5 minutes of exercise,four times a day(3 hours between sessions),at a speed of 11 m/min.Mice in the high-intensity cumulative exercise group exercised for 7.5 minutes once,four times a day(3 hours between sessions),at a speed of 19 m/min.At 48 hours after the final session,the levels of lipopolysaccharide and D-lactic acid in serum of mice were detected,the pathological changes of ileal tissue were observed by hematoxylin-eosin staining,and the expression of intestinal compact linking protein was detected by western blot.The expression of interleukin-10,tumor necrosis factor αin blood and ileum and intestinal secreted immunoglobulin A were detected by ELISA. RESULTS AND CONCLUSION:High-fat diet-induced insulin resistance was associated with body mass gain.The serum levels of endotoxin and D-lactic acid significantly increased,and the levels of tumor necrosis factor-α in serum and small intestine were significantly increased.Long-term regular cumulative exercise and continuous exercise could reduce the body mass of insulin-resistant mice,significantly improve glucose metabolism,and correct or improve insulin resistance symptoms.Both long-term regular cumulative exercise and continuous exercise could increase the expression of zonula occludens protein 1 and increase the secretion of secreted immunoglobulin A in intestinal mucosal tissue,thereby improving intestinal mucosal permeability,enhancing intestinal immune function,reducing the content of lipopolysaccharide in serum,and reducing the expression of pro-inflammatory factors in circulating blood and intestinal tissue.Finally,it could protect the intestinal mucosal barrier of insulin-resistant mice.Compared with medium-intensity cumulative exercise and continuous exercise,high-intensity cumulative exercise had more obvious effects on reducing body mass,improving insulin resistance symptoms and protecting intestinal mucosal barrier in insulin-resistant mice.
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Objective To study the effect of dual-mediated brain targeting liposomes(RVGPR9-SSL)as delivery vehicles on the blood brain barrier(BBB)permeability of doxorubicin(DOX),providing a new strategy for brain drug delivery.Methods The dual-mediated brain targeting liposomes(RVGPR9-SSL)were prepared by thin film dispersion/leading compound method.And the chemo-therapeutic drug DOX was encapsulated in RVGPR9-SSL(DOX@RVGPR9-SSL).Brain microvascular endothelial cells(BMVEC)were cultured and used to construct in vitro BBB models.The BBB model was then evaluated by a 4h leakage test,transmembrane resist-ance value(TEER)measurement,and tight junctions between cells observed by scanning transmission electron microscope(SEM).After the successful construction of the BBB model,the integrity of RVGPR9-SSL after crossing the BBB was investigated by confocal laser scanning microscopy using fluorescence a resonance energy transfer(FRET)pair.The effect of RVGPR9-SSL administration on BBB in-tegrity was evaluated by comparative analysis of BBB morphology and TEER values before and after liposome administration.The BBB per-meability of DOX@RVGPR9-SSL was investigated by fluorescence spectrophotometry.Results The encapsulation efficiency of DOX@RVGPR9-SSL was 97.25%.The TEER values of the constructed BBB model were all greater than 200Ω·cm2,and it was observed by SEM that the BMVEC cells were closely arranged and there were obvious tight junctions,indicating that the in vitro BBB model was suc-cessfully established and could be used for the investigation of BBB permeability.The 4h BBB cumulative permeability of DOX@RVGPR9-SSL was greater than 10%,which was significantly higher than that of free DOX.And both BBB and liposomes maintained good integrity after administration.Conclusion RVGPR9-SSL can significantly improve the BBB permeability of DOX,indicating that it is a very promising brain drug delivery vehicle.
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Objective To develop an oxybutynin nanotransdermal formulation with high skin permeability based on cubsomes carrier.Methods The oxybutynin loaded cubsomes(OXY-CS)was prepared by ultrasonic method.Using particle size,polydispersity index and encapsulation efficiency as evaluation indexes,stirring temperature,stirring time,stirring speed,ultrasound time,ultrasound power,glycerol monooleate/poloxamer 407 ratio(GMO/F127),carrier(GMO+F127)/drug ratio and drug concentration were optimized.The effects of drug concentration,permeation promoter and gel matrix type on skin permeability were investigated using cumulative permeation and skin retention as evaluation indicators.Results The prepared OXY-CS had small particle size and high encapsulation efficiency at stirring temperature of 50℃,stirring time of 30 min,stirring speed of 1 000 r/min,ultrasound time of 10 min,ultrasound power of 100 W,GMO/F127 ratio of 2∶1,carrier/drug ratio of 3∶1 and drug concentration of 1%,respectively.OXY-CS had high cumulative penetration and skin retention at concentration ≥ 3%.The addition of a permeation promoter to OXY-CS did not increase the cumulative penetration of the drug.The skin permeability of oxybutynin cubsomes gel made with carbomer was significantly better than those of other gel matrices.Conclusion In this study,oxybutynin is made into a topical cubsomes gel,which is expected to reduce the incidence of adverse effects associated with oral administration.
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OBJECTIVE@#The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide (LPS) induced septic cardiac dysfunction.@*METHODS@#Specific pathogen-free chicken embryos ( n = 120) were allocated untreated control, phosphate buffer solution (PBS) vehicle, PBS with ethanol vehicle, LPS (500 ng/egg), LPS with quercetin treatment (10, 20, or 40 nmol/egg, respectively), Quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity. At embryonic day 19, the hearts of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, immunohistochemical investigations, and Western blotting.@*RESULTS@#They demonstrated that the heart presented inflammatory responses after LPS induction. The LPS-induced higher mRNA expressions of inflammation-related factors (TLR4, TNFα, MYD88, NF-κB1, IFNγ, IL-1β, IL-8, IL-6, IL-10, p38, MMP3, and MMP9) were blocked by quercetin with three dosages. Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of TLR4, IFNγ, MMP3, and MMP9 when compared with the LPS group. Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1, and significantly decreased protein expression of claudin 1 when compared with the LPS group. Quercetin significantly downregulated autophagy-related gene expressions (PPARα, SGLT1, APOA4, AMPKα1, AMPKα2, ATG5, ATG7, Beclin-1, and LC3B) and programmed cell death (Fas, Bcl-2, CASP1, CASP12, CASP3, and RIPK1) after LPS induction. Quercetin significantly decreased immunopositivity to APOA4, AMPKα2, and LC3-II/LC3-I in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of AMPKα1, LC3-I, and LC3-II. Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.@*CONCLUSION@#Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy, programmed cell death, and myocardiocytes permeability.
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Embryon de poulet , Animaux , Quercétine/usage thérapeutique , Lipopolysaccharides/toxicité , Matrix metalloproteinase 9 , Caspase-3 , Matrix metalloproteinase 3 , Récepteur de type Toll-4 , Claudine-1 , Inflammation/métabolisme , Apoptose , ARN messager , Autophagie , Facteur de transcription NF-kappa BRésumé
Abstract This study aimed to evaluate the effects of the application of 10% sodium ascorbate (SA) after in-office bleaching on the penetration of hydrogen peroxide (HP) into the pulp chamber, color change, and microtensile bond strength (µTBS) to the resin-enamel interface. Thirty premolars and thirty molars were randomly divided into three groups (n = 20 each). One group was exposed to deionized water (negative control). The other two groups were bleached with 35% HP in a single session for 3x15 minutes for each application. However, in only one of them, SA was applied for 10 minutes after bleaching. After, the concentration (µg/mL) of HP in each pulp chamber was evaluated by UV-Vis spectrophotometry. Color changes (ΔEab, ΔE00, and ΔWID) were evaluated with a digital spectrophotometer before and in the first week after bleaching. After treatment, molars were restored and sectioned to obtain resin-enamel interface sticks for µTBS at a crosshead speed of 1 mm/min until failure. The HP concentration and µTBS data were analyzed using one-way ANOVA and Tukey tests, and color changes were analyzed by t-tests (α = 0.05). SA application significantly improved the µTBS values and reduced the HP concentrations within the pulp chambers (p < 0.0001). The application of SA significantly interfered with the color changes after bleaching when compared to the control group (p < 0.05). Application of 10% SA after in-office bleaching successfully reduced the penetration of HP into the pulp chamber; however, it decreased color change.
Resumo Este estudo teve como objetivo avaliar os efeitos da aplicação do ascorbato de sódio a 10% (AS) depois do clareamento em consultório na penetração do peróxido do hidrogênio (PH) na câmara pulpar, mudança de cor e resistência de união (RU) da interface resina-esmalte. Trinta pré-molares e trinta molares foram divididos aleatoriamente em três grupos (n = 20). Um grupo foi exposto em água deionizada (controle negativo). Os outros dois grupos foram clareados com 35% PH numa única sessão de 3x15 minutos para cada aplicação. Porém, só um grupo recebeu AS durante 10 minutos depois do clareamento. Depois, a concentração (µg/mL) do PH no interior de cada câmara pulpar foi avaliado com espectrofotometria UV-Vis. A mudança de cor (ΔEab, ΔE00 and ΔWID) foi avaliada como espectrofotômetro digital antes e depois de uma semana do clareamento. Após de cada tratamento, os molares foram restaurados e seccionados em espécimes com interface resina-esmalte para o teste de RU por microtração a uma velocidade de 1 mm/min até a fratura. Os dados da concentração de PH e RU foram analisados usando ANOVA de uma via e teste de Tukey, e a mudança de cor com o teste t (α = 0.05). A aplicação de AS melhorou significativamente a RU e reduziu a concentração de PH na câmara pulpar (p < 0.0001). A aplicação de AS interferiu significativamente na mudança de cor depois do clareamento comprado com o grupo controle (p < 0.05). A aplicação de SA a 10% depois do clareamento em consultório reduziu significativamente a penetração do PH na câmara pulpar e interferiu na mudança de cor.
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Comparar la permeabilidad de las vías aéreas y el tamaño de los senos maxilares en relación con la clase esqueletal. se midieron 90 radiografías lateral de cráneo, divididas en 3 grupos, comparando las 3 clases esqueletales, las cuales se determinaron con la medida ANB de Steiner, y estas a su vez en dos subgrupos que fueron hombres y mujeres, en las cuales se utilizó el análisis de McNamara para el análisis de vías aéreas y para el área del seno maxilar se tomaron dos medidas una antero-posterior y cefálica-caudal. Al comparar los hombres con las mujeres se identificó significancia estadística en vía área superior de clase II (p=≤0.017), vía aérea inferior de clase III (p=≤0.006). Al comparar las clases esqueletales en hombres se identificó diferencias en la vía aérea superior en las clases I vs III (p=≤0.05), inferior en la clase I vs III (p=≤0,001) y II vs III (p=≤0.044). Con respecto a mujeres se identificó significancia en la vía aérea superior al comparar la clase I vs II (p=≤0,043), vía aérea inferior en la clase II vs III (p=≤0.05), longitud del seno maxilar al comparar clase I vs II (p=≤0.017). Entre la clase I esqueletal y la clase II, el tamaño de los senos maxilares resulto menor en longitud en las mujeres de clase II esqueletal. Entre la clase I y clase III esqueletal en hombres, se encontró una longitud menor en la vía aérea superior e inferior en la clase I. Las vías aéreas resultaron en menor tamaño en sujetos de clase II.
SUMMARY: To compare the airway permeability and the size of the maxillary sinuses in relation to the skeletal class. 90 lateral skull radiographs were divided into 3 groups, comparing the 3 skeletal classes, which were determined with Steiner's ANB measurement, and these were once in two subgroups that were men and women, in any McNamara analysis was used for the analysis of airways and for the maxillary sinus area measurements were made an antero-posterior and cephalic-caudal. When comparing males with females, statistical significance was identified in the upper class II route (p=≤0,017), lower class III airway (p=≤0.006). At least skeletal classes in men, differences were identified in the upper airway in classes I vs III (p=≤0.05), lower in class I vs III (p=≤0.001) and II vs III (p=≤0.044). With respect to women, significance was identified in the upper airway when comparing class I vs II (p=≤0.043), lower airway in class II vs. III (p=≤0.05), maxillary sinus length to class I vs II (p=≤0.017). Between skeletal class I and class II, maxillary sinus size was shorter in length in skeletal class II women. Between class I and skeletal class III in men, a lower length was found in the upper and lower airways in class I. The airways were found to be smaller in class II subjects.
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Humains , Mâle , Femelle , Perméabilité , Partie nasale du pharynx/imagerie diagnostique , Sinus maxillaire/imagerie diagnostique , Partie nasale du pharynx/anatomie et histologie , Malocclusion de classe I , Malocclusion de classe II , Malocclusion de classe III , Sinus maxillaire/anatomie et histologie , MexiqueRésumé
Objective:To investigate the predictive value of thrombus enhancement (TE) and thrombus permeability in cardioembolic thrombus with acute middle cerebral artery occlusion based on CT.Methods:The clinical and image data of 93 patients with acute middle cerebral artery occlusion who were admitted to the First Affiliated Hospital of Soochow University within 12 hours after onset from January 2020 to July 2022 were retrospectively analyzed. According to the TOAST criteria, the patients were divided into the cardioembolism (CE) group (43 cases) and the large artery atherosclerosis (LAA) group (50 cases). All patients received noncontrast CT and CT angiography, and then thrombus permeability [thrombus attenuation increase (TAI), void fraction (ε)] and TE were assessed. Independent sample t-test, Mann-Whitney U test and χ2 test were used in univariable analysis between two groups. Multivariable logistic regression analysis was used to explore the independent influencing factors for cardioembolic stroke and establish a logistic model. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the predictive value of TAI, ε, TE and the logistic model in cardioembolic thrombus with acute middle cerebral artery occlusion. Results:There were statistically significant differences in sex, atrial fibrillation, hypertension, diabetes mellitus, smoking, baseline National Institutes of health stroke scale (NIHSS), TAI, ε and TE between the CE group and the LAA group ( P<0.05). Binary logistics regression analysis showed that TAI (OR=1.300, 95%CI 1.147-1.473, P<0.001), hypertension (OR=0.116, 95%CI 0.025-0.535, P=0.006) and baseline NIHSS (OR=1.165, 95%CI 1.040-1.304, P=0.008) were independent influencing factors for cardioembolic thrombus. The ROC curve indicated that the logistic model predicted cardioembolic thrombus with the highest AUC of 0.907 (95%CI 0.848-0.966). TE predicted cardioembolic thrombus with the highest sensitivity of 90.7%. Conclusion:TE and thrombus permeability have application value for predicting cardioembolic thrombus with acute middle cerebral artery occlusion based on CT.
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Objective:To investigate the value of enhanced MRI in evaluating the tissue permeability of pancreatic ductal adenocarcinoma (PDAC) animal model.Methods:The experimental animals were 27 female C57BL/6 mice. The mice were divided into 3 groups with 9 mice in each group by random number method. Murine pancreatic adenocarcinoma (Panc02) and embryonic fibroblasts (NIH/3T3) were implanted subcutaneously at the ratio of 2∶1 and 1∶1 to establish PDAC models with different tissue permeability, which were low fibroblast group and high fibroblast group, respectively, and simple Panc02 implantation model was control group. The positive expression rate of α-smooth muscle actin (α-SMA), the positive expression rate of fibroblast activating protein (FAP), the coverage rate of collagen fibers, number of blood vessels and the long/short diameter of tissue vessels were quantitatively evaluated by tissue staining, and the tissue permeation efficiency was quantified by the average optical density (AOD) of tissue sections stained by Evans blue (EB). Enhanced MRI was performed on mice, and the enhancement degree and the enhancement rate of 20 min were obtained. One-way ANOVA was used to compare the overall differences of tumor histological indexes and MRI enhancement parameters in each group, and the correlation between the indexes was analyzed by Pearson correlation analysis. Multiple linear stepwise regression analysis was conducted with 20 min enhancement rate as dependent variable, while α-SMA positive expression rate, collagen fiber coverage rate and vascular long/short diameter as independent variables.Results:There were significant differences in AOD value, α-SMA positive expression rate, FAP positive expression rate, collagen fiber coverage rate, vascular long/short diameter, 20 min enhancement degree and 20 min enhancement rate among the three groups ( P<0.001), but there was no significant difference in the number of blood vessels ( P=0.650). The AOD value was negatively correlated with the positive expression rate of α-SMA, the coverage rate of collagen fibers and the long/short diameter of blood vessels in PDAC model, respectively ( r=-0.888, P=0.001; r=-0.813, P=0.008; r=-0.915, P<0.001). The 20 min enhancement degree was positively correlated with AOD value ( r=0.954, P<0.001). The positive expression rate of α-SMA, collagen fiber coverage and vascular long/short diameter were negatively correlated with 20 min enhancement rate ( r=-0.901, P<0.001; r=-0.837, P=0.005; r=-0.880, P=0.002). The results of multiple linear stepwise regression analysis showed that the positive expression rate of α-SMA was an important influencing factor for the 20 min enhancement rate (R 2=0.813, P=0.001). Conclusions:The increase of fibroblast implantation ratio significantly decreased the permeation efficiency of tumor tissue. The positive expression rate of α-SMA, the coverage rate of collagen fibers and the long/short diameter of blood vessels were negatively correlated with the permeation efficiency of tumor tissue. The 20 min enhancement degree was positively correlated with tissue permeation efficiency.
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Objective:To determine whether the transepidermal water loss rate (TEWL) is correlated with the stratum corneum (SC) hydration level.Methods:Healthy children aged ≤ 17 years were enrolled from Medical Center for Public Health of Puning, 2 kindergartens and 2 primary schools, from October 2021 to June 2022. TEWL and SC hydration levels were measured on the left forearm and right anterior shank using a device for measuring skin physiological funcitons. Pearson correlation analysis was used to determine the correlations between TEWL and SC hydration levels in children of different ages and genders.Results:A total of 1 396 healthy children were enrolled, aged from 1 month to 17 years. Among them, 783 were male children and 613 were female children. In children aged 1 to < 12 months, no correlation was observed between TEWL and SC hydration levels on the forearms of male children, while TEWL was positively correlated with SC hydration levels on the anterior shanks of male children, as well as on the forearm and anterior shanks of female children ( r = 0.283, 0.404, 0.420, respectively, all P < 0.05) . In children aged 1 to 2 years, positive correlations were observed between the above two indicators on the anterior shanks of male children and forearms of female children ( r = 0.370, 0.419, respectively, both P < 0.01) , while there were no correlations between the two indicators on the anterior shanks of female children or forearms of male children. Positive correlations were observed between TEWL and SC hydration levels on both the forearms and anterior shanks of female children and the forearms of male children aged 3 to 5 years and 6 to 11 years ( r values ranging from 0.172 to 0.293, all P < 0.05) , but not on the anterior shanks of male children aged from 6 to 11 years. The group aged 12 to 17 years exhibited significantly positive correlations between TEWL and SC hydration levels on both the anterior shanks and forearms of male and female children ( r values ranging from 0.269 to 0.485, all P < 0.001) . Conclusion:SC hydration levels are positively correlated with TEWL on the anterior shanks and forearms of healthy children, and the degree of correlation tends to increase with age.
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Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of systemic small vasculitis characterized by the detection of ANCA in serum. Bactericidal permeability enhancing protein (BPI) is one of the target antigens of ANCA. BPI-ANCA-associated vasculitis is not common clinically, and the combination of bronchiectasis is not accidental. The paper reported a case of BPI-ANCA-associated vasculitis with renal damage combined with bronchiectasis. We reviewed relevant literature to explore the characteristics of BPI-ANCA-associated vasculitis and the correlation between bronchiectasis and ANCA-associated vasculitis, so as to improve the clinician's understanding on this disease.
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@#As a new research field,gel has been paid more attention and widely used for studies on tissue engineering,drug delivery and biosensor. Hydrogel is the carrier of cells,while the cell survival and death are keys to the construction of tissues and organs. However,the cell viability and biological behavior are limited by the exchange of hydrogel and nutrients in medium. This review summarizes the types of hydrogel,exchange mode of hydrogel and nutrients in medium and the relevant influencing factors,which will provide a reference for the development and research of tissue bioengineering.
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ObjectiveTo investigate the efficacy of Huangqintang on mouse models of colitis-associated colon cancer (CAC) and explore the mechanism of Huangqintang in regulating immune function and inflammatory response, inhibiting abnormal cell proliferation, and delaying or inhibiting CAC formation in CAC. MethodC57BL/6J mice were randomly divided into a normal group, model group, mesalazine group, and high- and low-dose Huangqintang groups according to body weight, with 12 mice in each group. Except for the normal group, the rest of the mice were given two intraperitoneal injections of 10 mg·kg-1 azomethane (AOM) and allowed to drink 1.5% dextran sodium sulfate (DSS) freely for seven days and water normally for two weeks. Then, two cycles of ''DSS-drinking water'' were repeated. During the administration of DSS, mice in the normal group and model group were given gavage in equal doses of pure water. Mice in the mesalazine group were given 150 mg·kg-1·d-1 mesalamine suspension for gavage, and mice in the high- and low-dose Huangqintang groups were given 18 and 9 g·kg-1·d-1 Huangqintang for gavage, respectively. Each group was given one dose daily until the end of three cycles. After the intervention, the body weight, colon length, and number of colon tumors in each group were measured, and disease activity index (DAI) scores were performed. The serum contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-10 (IL-10), and gastrointestinal tumor marker carbohydrate antigen-199 (CA199) were detected by enzyme linked immunosorbent assay (ELISA). The colonic lesions were observed by hematoxylin-eosin (HE) staining. The expression of proliferative cell-associated antigen (Ki67) was observed by immunohistochemistry. The expression of T lymphocyte subsets (CD3+, CD4+, CD8+, and CD49b+) in mouse plasma was detected by flow cytometry. Fluorescein isothiocyanate-D (FITC-D) content in mouse serum was detected by fluorescent labeling method. The Western blot method was used to detect the expression of Cyclin D1, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and tightly junction-related Occludin and Claudin-1. ResultCompared with the normal group, the body weight of mice in the model group decreased. DAI score increased significantly, and the colon became shorter. Pro-inflammatory factors such as IL-6, TNF-α, and IL-1β increased, and IL-6 and TNF-α were significantly increased (P<0.05). The inflammatory factor IL-4 (P<0.05) and IL-10 were significantly reduced, and the tumor marker CA199 was significantly increased (P<0.01). HE staining showed that colon lesions, intestinal mucosal epithelial defects with a large number of inflammatory infiltrates, serious crypt structure damage, and glandular arrangement disorder were observed in the model group. Ki67 positive granules were expressed in large areas of colonic tissue. The serum CD4+ and CD4+/CD8+ of mice in the model group decreased significantly (P<0.05), and CD8+ increased significantly (P<0.05). The plasma content of FITC-D in the model group was significantly increased (P<0.05), and the expression of Cyclin D1, CDK2, and CDK4 proteins in colon tissue was significantly increased (P<0.05, P<0.01). In addition, the expression of Occludin and Claudin-1 was significantly decreased. Compared with the model group, the body weight of mice in the mesalazine group and the high- and low-dose Huangqintang groups increased. DAI score decreased, and the colon became longer. IL-6, TNF-α, and IL-1β expression decreased (P<0.05, P<0.01), but there was no significant change in IL-4 and IL-10. The content of CA199 was significantly reduced (P<0.05), and the colomatoid lesions and inflammatory infiltrates were reduced in the mesalazine group and the Huangqintang group. The crypt structure damage was lighter, and the positive expression of Ki67 was reduced. CD4+, CD4+/CD8+, and CD49b+ increased, and the difference was not statistically significant. FITC-D content decreased (P<0.05). The expression of Cyclin D1, CDK2, and CDK4 decreased (P<0.05, P<0.01), and Claudin-1 and Occludin protein expression increased in the high-dose Huangqintang group (P<0.05). ConclusionHuangqintang has a certain delay and inhibitory effect on AOM/DSS-induced inflammatory cancer transformation, and its mechanism of action may be related to regulating immune function and inflammatory response, inhibiting the release of pro-inflammatory factors, repairing damaged intestinal barriers, inhibiting abnormal proliferation of colon cells, and intervening in the formation and development of CAC colon tumors.
Résumé
Objective To evaluate the protective effect and the underlying mechanism of mesenchymal stem cell-derived extracellular vesicle (MSC-EV) on radiation-induced liver injury and liver cell line injury in mouse models. Methods C57BL/6 mice were randomly divided into the blank group, model group and MSC-EV treatment group (treatment group), with 9 mice in each group. AML12 cells were randomly divided into the control group, irradiation group and MSC-EV intervention group (intervention group). Animal and cell models with radiation-induced injury were established by one-time 15 Gy and 6 Gy X-ray irradiation, respectively. At 48 h after irradiation, liver tissues and serum samples of mice were collected and prepared for subsequent experiments. At 15 h post-irradiation, cell experiment was carried out. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and content of malondialdehyde (MDA) in liver tissues and cells were measured. The relative expression levels of interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β and CXC chemokine ligand (CXCL)10 messenger RNA (mRNA) were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Liver tissues were prepared for hematoxylin-eosin (HE) staining to calculate liver pathological injury score. The apoptosis of liver tissues and cells was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and propidiumiodide (PI) staining, respectively. The expression levels of glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) proteins were detected by Western blot. The production level of reactive oxygen species (ROS) was detected by dihydroethidine (DHE) staining. The fluorescence intensity of mitochondrial permeability transition pore (mPTP) was determined. Results Compared with the blank group, serum levels of AST and ALT were up-regulated, and the relative expression levels of IL-1β, TGF-β and CXCL10 mRNA in the mouse liver tissues were up-regulated, and MDA content was increased, liver injury score was elevated, cell apoptosis rate was increased, intracellular ROS level was elevated, and the relative expression levels of GPX4 and FSP1 proteins in the mouse liver tissues were down-regulated in the model group, and the differences were statistically significant (all P<0.05). Compared with the model group, serum levels of AST and ALT were decreased, and the relative expression levels of IL-1β, TGF-β and CXCL10 mRNA in the liver tissues of mice were down-regulated, MDA content was declined, liver injury score was declined, cell apoptosis rate was decreased, intracellular ROS level was decreased, and the relative expression levels of GPX4 and FSP1 proteins in the liver tissues of mice were up-regulated in the treatment group, and the differences were statistically significant (all P<0.05). Compared with the control group, cell apoptosis rate was increased, intracellular ROS level was elevated, the fluorescence intensity of mPTP was weakened, the relative expression levels of IL-1β, TGF-β and IL-6 mRNA were up-regulated, MDA content was increased, and the relative expression levels of GPX4 and FSP1 proteins were down-regulated in the irradiation group, and the differences were statistically significant (all P<0.05). Compared with the irradiation group, cell apoptosis rate was declined, intracellular ROS level was decreased, the fluorescence intensity of mPTP was strengthened, the relative expression levels of IL-1β, TGF-β and IL-6 mRNA were down-regulated, MDA content was decreased and the relative expression levels of GPX4 and FSP1 proteins were up-regulated in the intervention group, and the differences were statistically significant (all P<0.05). Conclusions MSC-EV may effectively alleviate radiation-induced liver injury by reducing ferroptosis of liver cells, enhancing antioxidant level and decreasing the production of lipid peroxide, thereby effectively alleviating radiation-induced liver injury.