Jatonik polyherbal mixture induced rat liver MMPT pore opening in normal Wistar rat: In vitro and in vivo studies / 中草药·英文版

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.

Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death / 生物医学与环境科学（英文）

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.

Study on the stability and H+ permeable membrane properties of polymersomes / 药学实践杂志

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.

Effects of the application of sodium ascorbate after in-office bleaching on the penetration of hydrogen peroxide, color change, and microtensile bond strength

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.

Análisis bidimensional de la permeabilidad de vías aéreas con el tamaño de senos maxilares y su relación con el desarrollo de la clase esqueletal en una población mexicana / Two-dimensional analysis of airway permeability with maxillary sinus size and its relationship with the development of skeletal class in a Mexican population

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.

Dentin permeability after pretreatment with titanium tetrafluoride and self-etching or universal adhesive systems

Aim: To evaluate dentin permeability after pretreatment with 2.5% aqueous solution of titanium tetrafluoride (TiF4), followed by a self-etching universal adhesive system. Methods: Forty dentin discs (1.5 mm thick) were randomly divided into groups according to the application or non-application of a pretreatment, and the type of adhesive system to be tested (two-step self-etching/ Clearfil SE Bond/ Kuraray Medical, or universal adhesive system/ Single Bond Universal/ 3M ESPE). Both sides of the discs were conditioned with 37% phosphoric acid to remove the smear layer. The first hydraulic conductivity measurement (L1) was performed in a permeability machine, under 5 PSI pressure. The samples were sanded again to form a standardized smear layer. The teeth designated for pre-treatment with TiF4 received the TiF4 solutions applied actively for 60 seconds, and the adhesive systems were applied according to the manufacturer's instructions. Then, a new hydraulic conductivity measurement (L2) was performed for the purpose of calculating the hydraulic conductance at a later time, considering the water viscosity and the thickness of the specimen. The percentage (L) of dentin permeability after application of the adhesive system was obtained (L (%) = [(L1-L2) x100] / L1). The Mann-Whitney non-parametric test was applied. Results: There was no difference between the two adhesive systems, or between the groups with or without pretreatment, as regards dentin permeability (p>0.05). Conclusion: Pretreatment with 2.5% TiF4 did not influence dentin permeability, irrespective of the adhesive system used

Zonulina e Presepsina Poderiam ser Biomarcadores e Alvos Terapêuticos para Miocardite Aguda? / Could Zonulin and Presepsin Be Biomarkers and Therapeutic Targets for Acute Myocarditis?

Resumo Fundamento O diagnóstico de miocardite aguda geralmente é feito diante de parâmetros clínicos e laboratoriais, podendo, por vezes, ser confundido com doenças que compartilham de características clínicas semelhantes, o que dificulta o diagnóstico. Sendo assim, o uso de biomarcadores mais específicos, para além dos clássicos como a troponina, acelerará o diagnóstico. Além disso, esses biomarcadores podem nos ajudar a compreender melhor o mecanismo de desenvolvimento da miocardite e, assim, prever resultados clínicos imprevisíveis. Objetivo Este estudo tem como objetivo revelar a possível relação entre permeabilidade intestinal e miocardite aguda. Métodos Neste estudo, buscamos avaliar os níveis séricos de zonulina e presepsina em 138 indivíduos consecutivos, incluindo 68 pacientes com miocardite e outros 70 usados como grupo controle, pareados por idade, sexo e fatores de risco cardiovascular. Valores de p < 0,05 foram considerados estatisticamente significativos. Resultados Em comparação com o grupo controle, zonulina e presepsina foram significativamente maiores no grupo de pacientes com miocardite (p < 0,001, para todos). Os níveis de zonulina foram positivamente correlacionados com presepsina, pico de CK-MB e níveis máximos de troponina (r = 0,461, p < 0,001; r = 0,744, p < 0,001; r = 0,627, p < 0,001; respectivamente). Na análise de regressão, presepsina e zonulina foram determinadas como preditores independentes para miocardite (OR de 1,002, IC de 95% 1,001-1,003, p = 0,025; OR de 12,331, IC de 95% 4,261-35,689; p < 0,001; respectivamente). O valor preditivo de miocardite aguda de presepsina e zonulina na análise da curva ROC foi estatisticamente significativo (p < 0,001, para ambos). Conclusão Este estudo mostrou que a zonulina e a presepsina podem ser biomarcadores para o diagnóstico de miocardite e também podem ser alvos terapêuticos para esclarecer o mecanismo de desenvolvimento da miocardite.

Abstract Background The diagnosis of acute myocarditis is usually made with clinical and laboratory parameters. This can sometimes be mixed up with diseases that have similar clinical features, making the diagnosis difficult. Therefore, the use of more specific biomarkers, in addition to the classically used biomarkers such as troponin, will accelerate the diagnosis. In addition, these biomarkers may help us to understand the mechanism of myocarditis development and thus predict unpredictable clinical outcomes. Objective This study aims to reveal the possible relationship between intestinal permeability and acute myocarditis. Methods In this study, we wanted to evaluate serum levels of zonulin and presepsin in 138 consecutive subjects, including 68 patients with myocarditis and another 70 as the control group, matched for age, gender, and cardiovascular risk factors. P-values <0.05 were considered to be statistically significant. Results Compared to the control group, zonulin and presepsin were significantly higher in the patient group with myocarditis (p < 0.001, for all). Zonulin levels were positively correlated with presepsin, peak CK-MB, and peak troponin levels (r = 0.461, p < 0.001; r = 0.744, p < 0.001; r = 0.627, p < 0.001; respectively). In regression analysis, presepsin and zonulin were determined as independent predictors for myocarditis (OR 1.002, 95% CI 1.001-1.003, p = 0.025; OR 12.331, 95% CI 4.261-35.689; p < 0.001; respectively). The predictive value of acute myocarditis of presepsin and zonulin in ROC curve analysis was statistically significant (p < 0.001, for both). Conclusion This study showed that zonulin and presepsin could be biomarkers that can be used in the diagnosis of myocarditis, and they can also be therapeutic targets by shedding light on the developmental mechanism of myocarditis.

Tritium permeation resistance of Al-Al₂O₃ coatings prepared by thermal spraying / 中国辐射卫生

@#<b>Objective</b> To make the preparation method for coatings more convenient in the field where the requirements for tritium permeation resistance are not high, this paper proposes a method for preparing Al-Al₂O₃ tritium permeation barriers by thermal spraying technology and conducts a performance analysis. <b>Methods</b> The tritium permeation resistance and adhesion of Al-Al₂O₃ coatings prepared by thermal spraying were verified by experiments. <b>Results</b> The tritium permeability was reduced by one order of magnitude after a 0.2-mm Al-Al₂O₃ coating was sprayed on the stainless steel surface, and the tritium permeation resistance had no significant improvement with the increase in coating thickness; the adhesion of the coating was determined in the range of 5-10 N by scratch tests. <b>Conclusion</b> In this paper, a simple preparation method for tritium permeation barrier is proposed, and the tritium permeation resistance performance of Al-Al₂O₃ coatings prepared by thermal spraying technology is determined, which provides a reference for the selection of tritium permeation barrier in the field of tritium-containing solid waste storage.

Protective effect and mechanism of mesenchymal stem cell-derived extracellular vesicle on radiation-induced liver injury / 器官移植

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.

Peptide-drug conjugates (PDCs): a novel trend of research and development on targeted therapy, hype or hope?

Peptide-drug conjugates (PDCs) are the next generation of targeted therapeutics drug after antibody-drug conjugates (ADCs), with the core benefits of enhanced cellular permeability and improved drug selectivity. Two drugs are now approved for market by US Food and Drug Administration (FDA), and in the last two years, the pharmaceutical companies have been developing PDCs as targeted therapeutic candidates for cancer, coronavirus disease 2019 (COVID-19), metabolic diseases, and so on. The therapeutic benefits of PDCs are significant, but poor stability, low bioactivity, long research and development time, and slow clinical development process as therapeutic agents of PDC, how can we design PDCs more effectively and what is the future direction of PDCs? This review summarises the components and functions of PDCs for therapeutic, from drug target screening and PDC design improvement strategies to clinical applications to improve the permeability, targeting, and stability of the various components of PDCs. This holds great promise for the future of PDCs, such as bicyclic peptide‒toxin coupling or supramolecular nanostructures for peptide-conjugated drugs. The mode of drug delivery is determined according to the PDC design and current clinical trials are summarised. The way is shown for future PDC development.

Changes of intestinal wall barrier function and its correlation with susceptibility to infection in patients with cirrhotic portal hypertension / 中华肝脏病杂志

Objective: To investigate the changes of intestinal wall barrier function and its correlation with infection occurrence in patients with cirrhotic portal hypertension. Methods: 263 patients with cirrhotic portal hypertension were split into: the clinically evident portal hypertension (CEPH) combined with infection group (n = 74); CEPH group (n = 104); and Non-CEPH group (n = 85). Among them, 20 CEPH patients and 12 non-CEPH patients in non-infection status were subjected to sigmoidoscopy. Immunohistochemical staining was used to detect the expression of trigger receptor-1 (TREM-1), CD68, CD14, the inducible nitric oxide synthase molecule, and Escherichia coli (E.coli) in the medullary cells of the colon mucosa. An enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of soluble myeloid cell trigger receptor-1 (sTREM-1), soluble leukocyte differentiation antigen-14 subtype (sCD14-ST) and intestinal wall permeability index enteric fatty acid binding protein (I-FABP). Fisher's exact probability method, one-way ANOVA, Kruskal-Wallis-H test, Bonferroni method, and Spearman correlation analysis were used for statistical analysis. Results: The serum sTREM-1 and I-FABP levels were higher in CEPH patients than those of non-CEPH patients in the non-infectious state (P < 0.05), but the difference in blood sCD14-ST levels was not statistically significant (P > 0.05). Serum levels of sTREM-1, sCD14-ST, and I-FABP in infected patients were higher than those in patients without a concurrent infection (P < 0.05). Serum sCD14-ST levels were positively correlated with serum sTREM-1, C-reactive protein (CRP), and procalcitonin (PCT), and sTREM-1 levels were also positively correlated with CRP and PCT (r > 0.5, P < 0.001). The rates of CD68, inducible nitric oxide synthase, CD14-positive cells, and E.coli-positive glands were higher in the intestinal mucosa of the CEPH group than those of the control group (P < 0.05). Spearman's correlation analysis showed that the rate of E.coli-positive glands in CEPH patients was positively correlated with the expression of molecular markers CD68 and CD14 in the lamina propria macrophages. Conclusion: Patients with cirrhotic portal hypertension have increased intestinal permeability and inflammatory cells, accompanied by bacterial translocation. Serum sCD14-ST and sTREM-1 can be used as indicators to predict and evaluate the occurrence of infection in patients with cirrhotic portal hypertension.

Study on deep brain magnetic stimulation method based on magnetic replicator / 生物医学工程学杂志

Existing neuroregulatory techniques can achieve precise stimulation of the whole brain or cortex, but high-focus deep brain stimulation has been a technical bottleneck in this field. In this paper, based on the theory of negative permeability emerged in recent years, a simulation model of magnetic replicator is established to study the distribution of the induced electric field in the deep brain and explore the possibility of deep focusing, which is compared with the traditional magnetic stimulation method. Simulation results show that a single magnetic replicator realized remote magnetic source. Under the condition of the same position and compared with the traditional method of stimulating, the former generated smaller induced electric field which sharply reduced with distance. By superposition of the magnetic field replicator, the induced electric field intensity could be increased and the focus could be improved, reducing the number of peripheral wires while guaranteeing good focus. The magnetic replicator model established in this paper provides a new idea for precise deep brain stimulation, which can be combined with neuroregulatory techniques in the future to lay a foundation for clinical application.

Research Progress on Capillary Leak Syndrome Associated with Hematopoietic Stem Cell Transplantation--Review / 中国实验血液学杂志

Capillary leak syndrome (CLS) is a clinical syndrome characterized by impairment of vascular endothelial barrier function, increased vascular permeability, and reversible systemic edema. It is one of the early fatal complications after hematopoietic stem cell transplantation. So far, the exact pathogenesis of CLS has not been elucidated, and the diagnostic criteria and treatment methods have not been unified. At present, it is believed that the fundamental cause of CLS is hypercytokinemia, and the core factor is high permeability of vascular endothelial cells. According to the clinical manifestations, the natural course of CLS can be divided into prodrome, leakage and recovery stages. As far as treatment is concerned, symptomatic and supportive treatment is dominant according to different characteristics of each stage. In this review, the pathogenesis, clinical manifestations, diagnosis and treatment of hematopoietic stem cell transplant-associated CLS were briefly summarized.

Resampling combined with stacking learning for prediction of blood-brain barrier permeability of compounds / 生物医学工程学杂志

It is a significant challenge to improve the blood-brain barrier (BBB) permeability of central nervous system (CNS) drugs in their development. Compared with traditional pharmacokinetic property tests, machine learning techniques have been proven to effectively and cost-effectively predict the BBB permeability of CNS drugs. In this study, we introduce a high-performance BBB permeability prediction model named balanced-stacking-learning based BBB permeability predictor(BSL-B3PP). Firstly, we screen out the feature set that has a strong influence on BBB permeability from the perspective of medicinal chemistry background and machine learning respectively, and summarize the BBB positive(BBB+) quantification intervals. Then, a combination of resampling algorithms and stacking learning(SL) algorithm is used for predicting the BBB permeability of CNS drugs. The BSL-B3PP model is constructed based on a large-scale BBB database (B3DB). Experimental validation shows an area under curve (AUC) of 97.8% and a Matthews correlation coefficient (MCC) of 85.5%. This model demonstrates promising BBB permeability prediction capability, particularly for drugs that cannot penetrate the BBB, which helps reduce CNS drug development costs and accelerate the CNS drug development process.

Muscone inhibits opening of mPTP to alleviate OGD/R-induced injury of HT22 cells / 中国中药杂志

This study aims to investigate the mechanism of muscone in inhibiting the opening of mitochondrial permeability transition pore(mPTP) to alleviate the oxygen and glucose deprivation/reoxygenation(OGD/R)-induced injury of mouse hippocampal neurons(HT22). An in vitro model of HT22 cells injured by OGD/R was established. CCK-8 assay was employed to examine the viability of HT22 cells, fluorescence microscopy to measure the mitochondrial membrane potential, the content of reactive oxygen species(ROS), and the opening of mPTP in HT22 cells. Enzyme-linked immunosorbent assay was employed to determine the level of ATP and the content of cytochrome C(Cyt C) in mitochondria of HT22 cells. Flow cytometry was employed to determine the Ca~(2+) content and apoptosis of HT22 cells. The expression of Bcl-2(B-cell lymphoma-2) and Bcl-2-associated X protein(Bax) was measured by Western blot. Molecular docking and Western blot were employed to examine the binding between muscone and methyl ethyl ketone(MEK) after pronase hydrolysis of HT22 cell proteins. After the HT22 cells were treated with U0126, an inhibitor of MEK, the expression levels of MEK, p-ERK, and CypD were measured by Western blot. The results showed that compared with the OGD/R model group, muscone significantly increased the viability, mitochondrial ATP activity, and mitochondrial membrane potential, lowered the levels of ROS, Cyt C, and Ca~(2+), and reduced mPTP opening to inhibit the apoptosis of HT22 cells. In addition, muscone up-regulated the expression of MEK, p-ERK, and down-regulated that of CypD. Molecular docking showed strong binding activity between muscone and MEK. In conclusion, muscone inhibits the opening of mPTP to inhibit apoptosis, thus exerting a protective effect on OGD/R-injured HT22 cells, which is associated with the activation of MEK/ERK/CypD signaling pathway.

Improvement of solubility of epimedium flavonoid secondary glycoside components by traditional Chinese medicine polysaccharides and its mechanism / 中国中药杂志

The poor solubility of insoluble components of traditional Chinese medicine(TCM) is an important factor restricting the development of its preparations. Natural polysaccharides of TCM can be used as functional components to increase the solubility of insoluble components. Epimedium flavonoid secondary glycoside components(EFSGC) have been shown to have positive effects on the prevention and treatment of osteoporosis, but they exhibit poor solubility. Therefore, the strategy of solubilizing EFSGC with TCM polysaccharides was adopted, and its effect on the permeability and stability of EFSGC was evaluated in this study. Based on the equilibrium solubility experiment of EFSGC, it was found that Panax notoginseng crude polysaccharide(PNCP) had the best solubilization effect on EFSGC among the ten kinds of TCM polysaccharides, which increased the solubility of EFSGC from 0.8 mg·mL~(-1) to 13.3 mg·mL~(-1). It should be noted that after the solubilization of EFSGC by preparation technology, the effects on permeability and stability should be considered. Therefore, this study also investigated these two properties. The results showed that PNCP increased the effective transmittance of EFSGC from 50.5% to 71.1%, which could increase the permeability of EFSGC significantly. At the same time, it could improve the stability of EFSGC in the simulated gastric juice environment. In order to explain the solubilization mechanism of PNCP on EGSGC, critical micelle concentration, particle size, potential, differential scanning calorimetry, and infrared spectroscopy were analyzed. It was preliminarily inferred that the mechanism was as follows: PNCP and EFSGC could self-assemble into aggregates for solubilization by intermolecular hydrogen bonding interaction in water. In summary, PNCP can not only improve the solubility of EFSGC but also improve its permeability and stability. This study lays the foundation for the application of TCM polysaccharides as a functional component to solubilize insoluble components.

Intervention Mechanism of Huangqintang on Intestinal Inflammation and Proliferation in Colitis-associated Colon Cancer / 中国实验方剂学杂志

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.

Progress in research on hydrogel and medium permeability / 中国生物制品学杂志

@#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.

Bactericidal permeability increasing protein-anti-neutrophil cytoplasmic antibody- associated vasculitis complicated with bronchiectasis: a case report and literature review / 中华肾脏病杂志

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.